TREMFYA 100mg injectible solution medication leaflet

Tremfya 100 mg solution for injection in pre-filled syringe

Tremfya 100 mg solution for injection in pre-filled pen

Tremfya 100 mg solution for injection in pre-filled syringe

Each pre-filled syringe contains 100 mg of guselkumab in 1 mL solution.

Tremfya 100 mg solution for injection in pre-filled pen

Each pre-filled pen contains 100 mg of guselkumab in 1 mL solution.

Guselkumab is a fully human immunoglobulin G1 lambda (IgG1λ) monoclonal antibody (mAb)produced in Chinese Hamster Ovary (CHO) cells by recombinant DNA technology.

For the full list of excipients, see section 6.1.

Solution for injection (injection)

The solution is clear and colourless to light yellow, with target pH of 5.8 and approximate osmolarityof 367.5 mOsm/L.

Plaque psoriasis

Tremfya is indicated for the treatment of moderate to severe plaque psoriasis in adults who arecandidates for systemic therapy.

Tremfya, alone or in combination with methotrexate (MTX), is indicated for the treatment of activepsoriatic arthritis in adult patients who have had an inadequate response or who have been intolerant toa prior disease-modifying antirheumatic drug (DMARD) therapy (see section 5.1).

Tremfya is indicated for the treatment of adult patients with moderately to severely active ulcerativecolitis who have had an inadequate response, lost response, or were intolerant to either conventionaltherapy, or a biologic treatment.

Tremfya is indicated for the treatment of adult patients with moderately to severely active Crohn’sdisease who have had an inadequate response, lost response, or were intolerant to either conventionaltherapy or a biologic treatment.

This medicinal product is intended for use under the guidance and supervision of a physicianexperienced in the diagnosis and treatment of conditions for which it is indicated.

Plaque psoriasis

The recommended dose is 100 mg by subcutaneous injection at Weeks 0 and 4, followed by amaintenance dose every 8 weeks (q8w).

Consideration should be given to discontinuing treatment in patients who have shown no responseafter 16 weeks of treatment.

The recommended dose is 100 mg by subcutaneous injection at Weeks 0 and 4, followed by amaintenance dose every 8 weeks. For patients at high risk for joint damage according to clinicaljudgement, a dose of 100 mg every 4 weeks (q4w) may be considered (see section 5.1).

Consideration should be given to discontinuing treatment in patients who have shown no responseafter 24 weeks of treatment.

The recommended induction dose is 200 mg administered by intravenous infusion at Week 0, Week 4and Week 8. See SmPC for Tremfya 200 mg concentrate for solution for infusion.

After completion of the induction dose regimen, the recommended maintenance dose starting at

Week 16 is 100 mg administered by subcutaneous injection every 8 weeks (q8w). Alternatively, forpatients who do not show adequate therapeutic benefit to induction treatment according to clinicaljudgement, a maintenance dose of 200 mg administered by subcutaneous injection starting at Week 12and every 4 weeks (q4w) thereafter, may be considered (see section 5.1). For the 200 mg dose, see

SmPC for Tremfya 200 mg solution for injection.

Immunomodulators and/or corticosteroids may be continued during treatment with guselkumab. Inpatients who have responded to treatment with guselkumab, corticosteroids may be reduced ordiscontinued in accordance with standard of care.

Consideration should be given to discontinuing treatment in patients who have shown no evidence oftherapeutic benefit after 24 weeks of treatment.

Either of the following two induction dose regimens are recommended:

- 200 mg administered by intravenous infusion at Week 0, Week 4, and Week 8. See SmPC for

Tremfya 200 mg concentrate for solution for infusion.or

- 400 mg administered by subcutaneous injection (given as two consecutive injections of 200 mgeach) at Week 0, Week 4 and Week 8. See SmPC for Tremfya 200 mg solution for injection.

After completion of the induction dose regimen, the recommended maintenance dose starting at

Week 16 is 100 mg administered by subcutaneous injection every 8 weeks (q8w). Alternatively, forpatients who do not show adequate therapeutic benefit to induction treatment according to clinicaljudgement, a maintenance dose regimen of 200 mg administered by subcutaneous injection starting at

Week 12 and every 4 weeks (q4w) thereafter, may be considered (see section 5.1). For the 200 mgdose, see SmPC for Tremfya 200 mg solution for injection.

Immunomodulators and/or corticosteroids may be continued during treatment with guselkumab. Inpatients who have responded to treatment with guselkumab, corticosteroids may be reduced ordiscontinued in accordance with standard of care.

Consideration should be given to discontinuing treatment in patients who have shown no evidence oftherapeutic benefit after 24 weeks of treatment.

If a dose is missed, the dose should be administered as soon as possible. Thereafter, dosing should beresumed at the regular scheduled time.

No dose adjustment is required (see section 5.2).

There is limited information in patients aged ≥ 65 years and very limited information in patients aged≥ 75 years (see section 5.2).

Tremfya has not been studied in these patient populations. These conditions are generally not expectedto have any significant impact on the pharmacokinetics of monoclonal antibodies, and no doseadjustments are considered necessary. For further information on elimination of guselkumab, seesection 5.2.

The safety and efficacy of Tremfya in children and adolescents below the age of 18 years have notbeen established. No data are available.

Subcutaneous use only. Sites for injection include the abdomen, thigh and back of the upper arm.

Tremfya should not be injected into areas where the skin is tender, bruised, red, hard, thick or scaly. Ifpossible, areas of the skin that show psoriasis should be avoided as injection sites.

After proper training in subcutaneous injection technique, patients may inject Tremfya if a physiciandetermines that this is appropriate. However, the physician should ensure appropriate medicalfollow-up of patients. Patients should be instructed to inject the full amount of solution according tothe ‘Instructions for use’ provided in the carton.

For instructions on preparation of the medicinal product before administration, see section 6.6.

Serious hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

Clinically important active infections (e.g. active tuberculosis, see section 4.4).

In order to improve the traceability of biological medicinal products, the name and the batch numberof the administered product should be clearly recorded.

Guselkumab may increase the risk of infection. Treatment should not be initiated in patients with anyclinically important active infection until the infection resolves or is adequately treated.

Patients treated with guselkumab should be instructed to seek medical advice if signs or symptoms ofclinically important chronic or acute infection occur. If a patient develops a clinically important orserious infection or is not responding to standard therapy, the patient should be monitored closely andtreatment should be discontinued until the infection resolves.

Pre-treatment evaluation for tuberculosis

Prior to initiating treatment, patients should be evaluated for tuberculosis (TB) infection. Patientsreceiving guselkumab should be monitored for signs and symptoms of active TB during and aftertreatment. Anti-TB therapy should be considered prior to initiating treatment in patients with a pasthistory of latent or active TB in whom an adequate course of treatment cannot be confirmed.

Serious hypersensitivity reactions, including anaphylaxis, have been reported in the post-marketingsetting (see section 4.8). Some serious hypersensitivity reactions occurred several days after treatmentwith guselkumab, including cases with urticaria and dyspnoea. If a serious hypersensitivity reactionoccurs, administration of guselkumab should be discontinued immediately and appropriate therapyinitiated.

Hepatic transaminase elevations

In psoriatic arthritis clinical studies, an increased incidence of liver enzyme elevations was observed inpatients treated with guselkumab q4w compared to patients treated with guselkumab q8w or placebo(see section 4.8).

When prescribing guselkumab q4w in psoriatic arthritis, it is recommended to evaluate liver enzymesat baseline and thereafter according to routine patient management. If increases in alanineaminotransferase [ALT] or aspartate aminotransferase [AST] are observed and drug-induced liverinjury is suspected, treatment should be temporarily interrupted until this diagnosis is excluded.

Prior to initiating therapy, completion of all appropriate immunisations should be consideredaccording to current immunisation guidelines. Live vaccines should not be used concurrently inpatients treated with guselkumab. No data are available on the response to live or inactive vaccines.

Before live viral or live bacterial vaccination, treatment should be withheld for at least 12 weeks afterthe last dose and can be resumed at least 2 weeks after vaccination. Prescribers should consult the

Summary of Product Characteristics of the specific vaccine for additional information and guidance onconcomitant use of immunosuppressive agents post-vaccination.

Polysorbate 80 content

This medicinal product contains 0.5 mg of polysorbate 80 (E433) in each pre-filled syringe/pre-filledpen which is equivalent to 0.5 mg/mL. Polysorbates may cause allergic reactions.

Interactions with CYP450 substrates

In a Phase I study in patients with moderate to severe plaque psoriasis, changes in systemic exposures(Cmax and AUCinf) of midazolam, S-warfarin, omeprazole, dextromethorphan, and caffeine after asingle dose of guselkumab were not clinically relevant, indicating that interactions betweenguselkumab and substrates of various CYP enzymes (CYP3A4, CYP2C9, CYP2C19, CYP2D6, and

CYP1A2) are unlikely. There is no need for dose adjustment when co-administering guselkumab and

CYP450 substrates.

Concomitant immunosuppressive therapy or phototherapy

In psoriasis studies, the safety and efficacy of guselkumab in combination with immunosuppressants,including biologics, or phototherapy have not been evaluated. In psoriatic arthritis studies,concomitant MTX use did not appear to influence the safety or efficacy of guselkumab.

In ulcerative colitis and Crohn’s disease studies, concomitant use of immunomodulators (e.g.,azathioprine [AZA]) or corticosteroids did not appear to influence the safety or efficacy ofguselkumab.

Women of childbearing potential should use effective methods of contraception during treatment andfor at least 12 weeks after treatment.

There are limited data from the use of guselkumab in pregnant women. Animal studies do not indicatedirect or indirect harmful effects with respect to pregnancy, embryonic/foetal development, parturitionor postnatal development (see section 5.3). As a precautionary measure, it is preferable to avoid theuse of Tremfya during pregnancy.

It is unknown whether guselkumab is excreted in human milk. Human IgGs are known to be excretedin breast milk during the first few days after birth, and decrease to low concentrations soon afterwards;consequently, a risk to the breast-fed infant during this period cannot be excluded. A decision shouldbe made whether to discontinue breast-feeding or to abstain from Tremfya therapy, taking into accountthe benefit of breast-feeding for the child and the benefit of therapy for the woman. See section 5.3 forinformation on the excretion of guselkumab in animal (cynomolgus monkey) milk.

The effect of guselkumab on human fertility has not been evaluated. Animal studies do not indicatedirect or indirect harmful effects with respect to fertility (see section 5.3).

Tremfya has no or negligible influence on the ability to drive and use machines.

The most common adverse reaction was respiratory tract infections (approximately 8% of patients inulcerative colitis studies, 11% of patients in the Crohn’s disease studies, and 15% of patients in thepsoriasis and psoriatic arthritis clinical studies).

The overall safety profile in patients treated with Tremfya is similar for patients with psoriasis,psoriatic arthritis, ulcerative colitis, and Crohn’s disease.

Table 1 provides a list of adverse reactions from psoriasis, psoriatic arthritis,ulcerative colitis, and Crohn’s disease clinical studies as well as adverse reactions reported frompost-marketing experience. The adverse reactions are classified by MedDRA System Organ Class andfrequency, using the following convention: very common (≥ 1/10), common (≥ 1/100 to < 1/10),uncommon (≥ 1/1 000 to < 1/100), rare (≥ 1/10 000 to < 1/1 000), very rare (< 1/10 000), not known(cannot be estimated from the available data). Within each frequency grouping, adverse reactions arepresented in order of decreasing seriousness.

Table 1: List of adverse reactions

System Organ Class Frequency Adverse reactions

Infections and infestations Very common Respiratory tract infections

Uncommon Herpes simplex infections

Uncommon Tinea infections

Uncommon Gastroenteritis

Immune system disorders Rare Hypersensitivity

Rare Anaphylaxis

Nervous system disorders Common Headache

Gastrointestinal disorders Common Diarrhoea

Skin and subcutaneous tissue Common Rashdisorders Uncommon Urticaria

Musculoskeletal and connective Common Arthralgiatissue disorders

General disorders and administration Uncommon Injection site reactionssite conditions

Investigations Common Transaminases increased

Uncommon Neutrophil count decreased

Transaminases increased

In two Phase III psoriatic arthritis clinical studies, through the placebo-controlled period, adversereactions of increased transaminases (includes ALT increased, AST increased, hepatic enzymeincreased, transaminases increased, liver function test abnormal, hypertransaminasaemia) werereported more frequently in the guselkumab-treated groups (8.6% in the 100 mg subcutaneous q4wgroup and 8.3% in the 100 mg subcutaneous q8w group) than in the placebo group (4.6%). Through 1year, adverse reactions of increased transaminases (as above) were reported in 12.9% of patients in theq4w group and 11.7% of patients in the q8w group.

Based on laboratory assessments, most transaminase increases (ALT and AST) were ≤ 3 x upper limitof normal (ULN). Transaminase increases from > 3 to ≤ 5 x ULN and > 5 x ULN were low infrequency, occurring more often in the guselkumab q4w group compared with the guselkumab q8wgroup (Table 2). A similar pattern of frequency by severity and by treatment group was observedthrough the end of the 2-year Phase III psoriatic arthritis clinical study.

Table 2: Frequency of patients with transaminase increases post-baseline in two Phase IIIpsoriatic arthritis clinical studies

Through Week 24a Through 1 yearb

Placebo guselkumab guselkumab guselkumab guselkumab

N=370c 100 mg q8w 100 mg q4w 100 mg q8w 100 mg q4w

N=373c N=371c N=373c N=371c

ALT>1 to ≤3 x ULN 30.0% 28.2% 35.0% 33.5% 41.2%>3 to ≤ 5 x ULN 1.4% 1.1% 2.7% 1.6% 4.6%>5 x ULN 0.8% 0.8% 1.1% 1.1% 1.1%

AST>1 to ≤3 x ULN 20.0% 18.8% 21.6% 22.8% 27.8%>3 to ≤ 5 x ULN 0.5% 1.6% 1.6% 2.9% 3.8%>5 x ULN 1.1% 0.5% 1.6% 0.5% 1.6%a placebo-controlled period.b patients randomised to placebo at baseline and crossed over to guselkumab are not included.c number of patients with at least one post-baseline assessment for the specific laboratory test within the time period.

In the psoriasis clinical studies, through 1 year, the frequency of transaminase increases (ALT and

AST) for the guselkumab q8w dose was similar to that observed for the guselkumab q8w dose in thepsoriatic arthritis clinical studies. Through 5 years, the incidence of transaminase elevation did notincrease by year of guselkumab treatment. Most transaminase increases were ≤ 3 x ULN.

In most cases, the increase in transaminases was transient and did not lead to discontinuation oftreatment.

In pooled Phase II and Phase III Crohn’s disease clinical studies, through the placebo-controlledinduction period (Week 0-12), adverse events of increased transaminases (includes ALT increased,

AST increased, hepatic enzyme increased, transaminases increased, and liver function test increased)were reported more frequently in the guselkumab treated groups (1.7% of patients) than in the placebogroup (0.6% of patients). In pooled Phase II and Phase III Crohn’s disease clinical studies, through thereporting period of approximately one year, adverse events of increased transaminases (includes ALTincreased, AST increased, hepatic enzyme increased, transaminases increased, hepatic functionabnormal, and liver function test increased) were reported in 3.4% of patients in the guselkumab200 mg subcutaneous q4w treatment group and 4.1% of patients in the guselkumab 100 mgsubcutaneous q8w treatment group compared to 2.4% in the placebo group.

Based on laboratory assessments in pooled Phase II and Phase III Crohn’s disease clinical studies, thefrequency of ALT or AST elevations were lower than those observed in psoriatic arthritis Phase IIIclinical studies. In pooled Phase II and Phase III Crohn’s disease clinical studies, through the placebo-controlled period (Week 12), ALT (< 1% of patients) and AST (< 1% of patients) elevations ≥ 3x

ULN were reported in guselkumab treated patients. In pooled Phase II and Phase III Crohn’s diseaseclinical studies, through the reporting period of approximately one year, ALT and/or AST elevations≥ 3x ULN were reported in 2.7% of patients in the guselkumab 200 mg subcutaneous q4w treatmentgroup and 2.6% of patients in the guselkumab 100 mg subcutaneous q8w treatment group compared to1.9% in the placebo group. In most cases, the increase in transaminases was transient and did not leadto discontinuation of treatment.

Neutrophil count decreased

In two Phase III psoriatic arthritis clinical studies, through the placebo-controlled period, the adversereaction of decreased neutrophil count was reported more frequently in the guselkumab-treated group(0.9%) than in the placebo group (0%). Through 1 year, the adverse reaction of decreased neutrophilcount was reported in 0.9% of patients treated with guselkumab. In most cases, the decrease in bloodneutrophil count was mild, transient, not associated with infection and did not lead to discontinuationof treatment.

Gastroenteritis

In two Phase III psoriasis clinical studies through the placebo-controlled period, gastroenteritisoccurred more frequently in the guselkumab-treated group (1.1%) than in the placebo group (0.7%).

Through Week 264, 5.8% of all guselkumab-treated patients reported gastroenteritis. Adversereactions of gastroenteritis were non-serious and did not lead to discontinuation of guselkumabthrough Week 264. Gastroenteritis rates observed in psoriatic arthritis clinical studies through theplacebo-controlled period were similar to those observed in the psoriasis clinical studies.

In two Phase III psoriasis clinical studies through Week 48, 0.7% of guselkumab injections and 0.3%of placebo injections were associated with injection site reactions. Through Week 264, 0.4% ofguselkumab injections were associated with injection site reactions. Injection site reactions weregenerally mild to moderate in severity; none were serious, and one led to discontinuation ofguselkumab.

In two Phase III psoriatic arthritis clinical studies through Week 24, the number of patients thatreported 1 or more injection site reactions was low and slightly higher in the guselkumab groups thanin the placebo group; 5 (1.3%) patients in the guselkumab q8w group, 4 (1.1%) patients in theguselkumab q4w group, and 1 (0.3%) patient in the placebo group. One patient discontinuedguselkumab due to an injection site reaction during the placebo-controlled period of the psoriaticarthritis clinical studies. Through 1 year, the proportion of patients reporting 1 or more injection sitereactions was 1.6% and 2.4% in the guselkumab q8w and q4w groups respectively. Overall, the rate ofinjections associated with injection site reactions observed in psoriatic arthritis clinical studies throughthe placebo-controlled period was similar to rates observed in the psoriasis clinical studies.

In the Phase III ulcerative colitis maintenance clinical study through Week 44, the proportion ofpatients that reported 1 or more injection site reactions to guselkumab was 7.9% (2.5% of injections)in the guselkumab 200 mg subcutaneous q4w group (guselkumab 200 mg was administered as two100 mg injections in the Phase III ulcerative colitis maintenance clinical study) and no injection sitereactions in the guselkumab 100 mg subcutaneous q8w group. Most injection site reactions were mildand none were serious.

In Phase II and Phase III Crohn’s disease clinical studies through Week 48, the proportion of patientsthat reported 1 or more injection site reactions to guselkumab was 4.1% (0.8% of injections) in thetreatment group which received guselkumab 200 mg intravenous induction followed by 200 mgsubcutaneous q4w, and 1.4% (0.6% of injections) of patients in the guselkumab 200 mg intravenousinduction followed by 100 mg subcutaneous q8w group. Overall injection site reactions were mild;none were serious.

In a Phase III Crohn’s disease clinical study through Week 48, the proportion of patients that reported1 or more injection site reactions to guselkumab was 7% (1.3% of injections) in the treatment groupwhich received 400 mg subcutaneous induction followed by 200 mg subcutaneous q4w and 4.3%(0.7% of injections) of patients in the 400 mg guselkumab subcutaneous induction followed by100 mg subcutaneous q8w group. Most injection site reactions were mild; none were serious.

The immunogenicity of guselkumab was evaluated using a sensitive and drug-tolerant immunoassay.

In pooled Phase II and Phase III analyses in patients with psoriasis and psoriatic arthritis, 5% (n=145)of patients treated with guselkumab developed antidrug antibodies in up to 52 weeks of treatment. Ofthe patients who developed antidrug antibodies, approximately 8% (n=12) had antibodies that wereclassified as neutralising, which equates to 0.4% of all patients treated with guselkumab. In pooled

Phase III analyses in patients with psoriasis, approximately 15% of patients treated with guselkumabdeveloped antidrug antibodies in up to 264 weeks of treatment. Of the patients who developedantidrug antibodies, approximately 5% had antibodies that were classified as neutralising, whichequates to 0.76% of all patients treated with guselkumab. Antidrug antibodies were not associated withlower efficacy or development of injection site reactions.

In pooled Phase II and Phase III analyses in patients with ulcerative colitis, approximately 12% (n=58)of patients treated with guselkumab for up to 56 weeks developed antidrug antibodies. Of the patientswho developed antidrug antibodies, approximately 16% (n=9) had antibodies that were classified asneutralising, which equates to 2% of all patients treated with guselkumab. Antidrug antibodies werenot associated with lower efficacy or the development of injection site reactions.

In pooled Phase II and Phase III analyses up to Week 48 in patients with Crohn’s disease who weretreated with intravenous induction followed by subcutaneous maintenance dose regimen,approximately 5% (n=30) of patients treated with guselkumab developed antidrug antibodies. Of thepatients who developed antidrug antibodies, approximately 7% (n=2) had antibodies that wereclassified as neutralising antibodies, which equates to 0.3% of guselkumab treated patients. In a

Phase III analysis up to Week 48 in patients with Crohn’s disease who were treated with subcutaneousinduction followed by subcutaneous maintenance dose regimen, approximately 9% (n=24) of patientstreated with guselkumab developed antidrug antibodies. Of these patients, 13% (n=3) had antibodiesthat were classified as neutralising antibodies, which equates to 1% of guselkumab treated patients.

Antidrug antibodies were not associated with lower efficacy or development of injection site reactions.

Reporting suspected adverse reactions after authorisation of the medicinal product is important. Itallows continued monitoring of the benefit/risk balance of the medicinal product. Healthcareprofessionals are asked to report any suspected adverse reactions via the national reporting systemlisted in Appendix V.

Guselkumab intravenous doses up to 1 200 mg as well as subcutaneous doses up to 400 mg at a singledosing visit have been administered in clinical studies without dose-limiting toxicity. In the event ofoverdose, the patient must be monitored for any signs or symptoms of adverse reactions andappropriate symptomatic treatment must be administered immediately.

Pharmacotherapeutic group: Immunosuppressants, interleukin inhibitors, ATC code: L04AC16.

Guselkumab is a human IgG1λ monoclonal antibody (mAb) that binds selectively to the interleukin 23(IL-23) protein with high specificity and affinity through the antigen binding site. IL-23 is a cytokinethat is involved in inflammatory and immune responses. By blocking IL-23 from binding to itsreceptor, guselkumab inhibits IL-23-dependent cell signalling and release of proinflammatorycytokines.

Levels of IL-23 are elevated in the skin of patients with plaque psoriasis. In patients with ulcerativecolitis or Crohn’s disease, levels of IL-23 are elevated in the colon tissue. In in vitro models,guselkumab was shown to inhibit the bioactivity of IL-23 by blocking its interaction with cell surface

IL-23 receptor, disrupting IL-23-mediated signalling, activation and cytokine cascades. Guselkumabexerts clinical effects in plaque psoriasis, psoriatic arthritis, ulcerative colitis, and Crohn’s diseasethrough blockade of the IL-23 cytokine pathway.

Myeloid cells expressing Fc-gamma receptor 1 (CD64) have been shown to be a predominant sourceof IL-23 in inflamed tissue in psoriasis, ulcerative colitis, and Crohn’s disease. Guselkumab hasdemonstrated in vitro blocking of IL-23 and binding to CD64. These results indicate that guselkumabis able to neutralise IL-23 at the cellular source of inflammation.

In a Phase I study, treatment with guselkumab resulted in reduced expression of IL-23/Th17 pathwaygenes and psoriasis-associated gene expression profiles, as shown by analyses of mRNA obtainedfrom lesional skin biopsies of patients with plaque psoriasis at Week 12 compared to baseline. In thesame Phase I study, treatment with guselkumab resulted in improvement of histological measures ofpsoriasis at Week 12, including reductions in epidermal thickness and T-cell density. In addition,reduced serum IL-17A, IL-17F and IL-22 levels compared to placebo were observed in guselkumabtreated patients in Phase II and Phase III plaque psoriasis studies. These results are consistent with theclinical benefit observed with guselkumab treatment in plaque psoriasis.

In psoriatic arthritis patients in Phase III studies, serum levels of acute phase proteins C-reactiveprotein, serum amyloid A, and IL-6, and Th17 effector cytokines IL-17A, IL-17F and IL-22 wereelevated at baseline. Guselkumab decreased the levels of these proteins within 4 weeks of initiation oftreatment. Guselkumab further reduced the levels of these proteins by Week 24 compared to baselineand also to placebo.

In patients with ulcerative colitis or Crohn’s disease, guselkumab treatment led to decreases ininflammatory markers including C-reactive protein (CRP) and faecal calprotectin through induction

Week 12, which were sustained through one year of maintenance treatment. Serum protein levels of

IL-17A, IL-22 and IFNγ were reduced as early as Week 4, and continued to decrease throughinduction Week 12. Guselkumab also reduced colon mucosal biopsy RNA levels of IL-17A, IL-22 and

IFNγ at Week 12.

Plaque psoriasis

The efficacy and safety of guselkumab was assessed in three randomised, double-blind, activecontrolled Phase III studies in adult patients with moderate to severe plaque psoriasis, who werecandidates for phototherapy or systemic therapy.

VOYAGE 1 and VOYAGE 2

Two studies (VOYAGE 1 and VOYAGE 2) evaluated the efficacy and safety of guselkumab versusplacebo and adalimumab in 1 829 adult patients. Patients randomised to guselkumab (N=825) received100 mg at Weeks 0 and 4, and every 8 weeks (q8w) thereafter through Week 48 (VOYAGE 1) and

Week 20 (VOYAGE 2). Patients randomised to adalimumab (N=582) received 80 mg at Week 0 and40 mg at Week 1, followed by 40 mg every other week (q2w) through Week 48 (VOYAGE 1) and

Week 23 (VOYAGE 2). In both studies, patients randomised to placebo (N=422) received guselkumab100 mg at Weeks 16, 20 and q8w thereafter. In VOYAGE 1, all patients, including those randomisedto adalimumab at Week 0, started to receive open-label guselkumab q8w at Week 52. In VOYAGE 2,patients randomised to guselkumab at Week 0 who were Psoriasis Area and Severity Index (PASI) 90responders at Week 28 were re-randomised to either continue treatment with guselkumab q8w(maintenance treatment) or receive placebo (withdrawal treatment). Withdrawal patients re-initiatedguselkumab (dosed at time of retreatment, 4 weeks later and q8w thereafter) when they experienced atleast a 50% loss of their Week 28 PASI improvement. Patients randomised to adalimumab at Week 0who were PASI 90 non-responders received guselkumab at Weeks 28, 32 and q8w thereafter. In

VOYAGE 2, all patients started to receive open-label guselkumab q8w at Week 76.

Baseline disease characteristics were consistent for the study populations in VOYAGE 1 and 2 with amedian body surface area (BSA) of 22% and 24%, a median baseline PASI score of 19 for bothstudies, a median baseline dermatology quality of life index (DLQI) score of 14 and 14.5, a baselineinvestigator global assessment (IGA) score of severe for 25% and 23% of patients, and a history ofpsoriatic arthritis for 19% and 18% of patients, respectively.

Of all patients included in VOYAGE 1 and 2, 32% and 29% were naïve to both conventional systemicand biologic therapy, 54% and 57% had received prior phototherapy, and 62% and 64% had receivedprior conventional systemic therapy, respectively. In both studies, 21% had received prior biologictherapy, including 11% who had received at least one anti-tumour necrosis factor alpha (TNFα) agent,and approximately 10% who had received an anti-IL-12/IL-23 agent.

The efficacy of guselkumab was evaluated with respect to overall skin disease, regional disease (scalp,hand and foot and nails) and quality of life and patient reported outcomes. The co-primary endpointsin VOYAGE 1 and 2 were the proportion of patients who achieved an IGA score of cleared orminimal (IGA 0/1) and a PASI 90 response at Week 16 versus placebo (see Table 3).

Overall skin disease

Treatment with guselkumab resulted in significant improvements in the measures of disease activitycompared to placebo and adalimumab at Week 16 and compared to adalimumab at Weeks 24 and 48.

The key efficacy results for the primary and major secondary study endpoints are shown in Table 3below.

Table 3: Summary of clinical responses in VOYAGE 1 and VOYAGE 2

Number of patients (%)

VOYAGE 1 VOYAGE 2

Placebo guselkumab adalimumab Placebo guselkumab adalimumab(N=174) (N=329) (N=334) (N=248) (N=496) (N=248)

Week 16

PASI 75 10 (5.7) 300 (91.2)a 244 (73.1)b 20 (8.1) 428 (86.3)a 170 (68.5)b

PASI 90 5 (2.9) 241 (73.3)c 166 (49.7)b 6 (2.4) 347 (70.0)c 116 (46.8)b

PASI 100 1 (0.6) 123 (37.4)a 57 (17.1)d 2 (0.8) 169 (34.1)a 51 (20.6)d

IGA 0/1 12 (6.9) 280 (85.1)c 220 (65.9)b 21 (8.5) 417 (84.1)c 168 (67.7)b

IGA 0 2 (1.1) 157 (47.7)a 88 (26.3)d 2 (0.8) 215 (43.3)a 71 (28.6)d

Week 24

PASI 75 - 300 (91.2) 241 (72.2)e - 442 (89.1) 176 (71.0)e

PASI 90 - 264 (80.2) 177 (53.0)b - 373 (75.2) 136 (54.8)b

PASI 100 - 146 (44.4) 83 (24.9)e - 219 (44.2) 66 (26.6)e

IGA 0/1 - 277 (84.2) 206 (61.7)b - 414 (83.5) 161 (64.9)b

IGA 0 - 173 (52.6) 98 (29.3)b - 257 (51.8) 78 (31.5)b

Week 48

PASI 75 - 289 (87.8) 209 (62.6)e - - -

PASI 90 - 251 (76.3) 160 (47.9)b - - -

PASI 100 - 156 (47.4) 78 (23.4)e - - -

IGA 0/1 - 265 (80.5) 185 (55.4)b - - -

IGA 0 - 166 (50.5) 86 (25.7)b - - -a p < 0.001 for comparison between guselkumab and placebo.b p < 0.001 for comparison between guselkumab and adalimumab for major secondary endpoints.c p < 0.001 for the comparisons between guselkumab and placebo for the co-primary endpoints.d comparisons between guselkumab and adalimumab were not performed.e p < 0.001 for comparison between guselkumab and adalimumab.

Response over time

Guselkumab demonstrated rapid onset of efficacy, with a significantly higher percent improvement in

PASI as compared with placebo as early as Week 2 (p < 0.001). The percentage of patients achieving a

PASI 90 response was numerically higher for guselkumab than adalimumab starting at Week 8 withthe difference reaching a maximum around Week 20 (VOYAGE 1 and 2) and maintained through

Week 48 (VOYAGE 1) (see Figure 1).

Figure 1: Percent of patients who achieved a PASI 90 response through week 48 by visit(patients randomised at Week 0) in VOYAGE 1

In VOYAGE 1, for patients receiving continuous guselkumab treatment, the PASI 90 response ratewas maintained from Week 52 through Week 252. For patients randomised to adalimumab at Week 0who crossed over to guselkumab at Week 52, the PASI 90 response rate increased from Week 52through Week 76 and was then maintained through Week 252 (see Figure 2).

Figure 2: Percent of patients who achieved a PASI 90 response by visit in the open-label phasein VOYAGE 1

The efficacy and safety of guselkumab was demonstrated regardless of age, gender, race, body weight,plaques location, PASI baseline severity, concurrent psoriatic arthritis, and previous treatment with abiologic therapy. Guselkumab was efficacious in conventional systemic-naive, biologic-naive, andbiologic-exposed patients.

In VOYAGE 2, 88.6% of patients receiving guselkumab maintenance treatment at Week 48 were

PASI 90 responders compared to 36.8% of patients who were withdrawn from treatment at Week 28(p < 0.001). Loss of PASI 90 response was noted as early as 4 weeks after withdrawal of guselkumabtreatment with a median time to loss of PASI 90 response of approximately 15 weeks. Among patientswho were withdrawn from treatment and subsequently re-initiated guselkumab, 80% regained a

PASI 90 response when assessed 20 weeks after initiation of retreatment.

In VOYAGE 2, among 112 patients randomised to adalimumab who failed to achieve a PASI 90response at Week 28, 66% and 76% achieved a PASI 90 response after 20 and 44 weeks of treatmentwith guselkumab, respectively. In addition, among 95 patients randomised to guselkumab who failedto achieve a PASI 90 response at Week 28, 36% and 41% achieved a PASI 90 response with anadditional 20 and 44 weeks of continued treatment with guselkumab, respectively. No new safetyfindings were observed in patients who switched from adalimumab to guselkumab.

Regional disease

In VOYAGE 1 and 2, significant improvements were seen in scalp, hand and foot, and nail psoriasis(as measured by the Scalp-specific Investigator Global Assessment [ss-IGA], Physician’s Global

Assessment of Hands and/or Feet [hf-PGA], Fingernail Physician’s Global Assessment [f-PGA] and

Nail Psoriasis Severity Index [NAPSI], respectively) in guselkumab treated patients compared toplacebo treated patients at Week 16 (p < 0.001, Table 4). Guselkumab demonstrated superioritycompared to adalimumab for scalp and hand and foot psoriasis at Week 24 (VOYAGE 1 and 2) and

Week 48 (VOYAGE 1) (p ≤ 0.001, except for hand and foot psoriasis at Week 24 [VOYAGE 2] and

Week 48 [VOYAGE 1], p < 0.05).

Table 4: Summary of regional disease responses in VOYAGE 1 and VOYAGE 2

VOYAGE 1 VOYAGE 2

Placebo guselkumab adalimumab Placebo guselkumab adalimumabss-IGA (N)a 145 277 286 202 408 194ss-IGA 0/1b, n (%)

Week 16 21 (14.5) 231 (83.4)c 201 (70.3)d 22 (10.9) 329 (80.6)c 130 (67.0)dhf-PGA (N)a 43 90 95 63 114 56hf-PGA 0/1b, n (%)

Week 16 6 (14.0) 66 (73.3)e 53 (55.8)d 9 (14.3) 88 (77.2)e 40 (71.4)df-PGA (N)a 88 174 173 123 246 124f-PGA 0/1, n (%)

Week 16 14 (15.9) 68 (39.1)e 88 (50.9)d 18 (14.6) 128 (52.0)e 74 (59.7)d

NAPSI (N)a 99 194 191 140 280 140

Percent Improvement, mean (SD)

Week 16 -0.9 (57.9) 34.4 (42.4)e 38.0 (53.9)d 1.8 (53.8) 39.6 (45.6)e 46.9 (48.1)da Includes only patients with ss-IGA, f-PGA, hf-PGA score ≥ 2 at baseline or baseline NAPSI score > 0.b Includes only patients achieving ≥ 2-grade improvement from baseline in ss-IGA and/or hf-PGA.c p < 0.001 for comparison between guselkumab and placebo for the major secondary endpoint.d comparisons between guselkumab and adalimumab were not performed.e p < 0.001 for comparison between guselkumab and placebo.

Health-related quality of life/Patient reported outcomes

Across VOYAGE 1 and 2 significantly greater improvements in health-related quality of life asmeasured by Dermatology Life Quality Index (DLQI) and in patient-reported psoriasis symptoms(itching, pain, burning, stinging and skin tightness) and signs (skin dryness, cracking, scaling,shedding or flaking, redness and bleeding) as measured by the Psoriasis Symptoms and Signs Diary(PSSD) were observed in guselkumab patients compared to placebo patients at Week 16 (Table 5).

Signs of improvement on patient-reported outcomes were maintained through Week 24 (VOYAGE 1and 2) and Week 48 (VOYAGE 1). In VOYAGE 1, for patients receiving continuous guselkumabtreatment, these improvements were maintained in the open-label phase through Week 252 (Table 6).

Table 5: Summary of patient reported outcomes at week 16 in VOYAGE 1 and

VOYAGE 2

VOYAGE 1 VOYAGE 2

Placebo guselkumab adalimum Placebo guselkumab adalimumabab

DLQI, patients170 322 328 248 495 247with baseline score

Change from baseline, mean (standard deviation)

Week 16 -0.6 (6.4) -11.2 (7.2)c -9.3 (7.8)b -2.6 (6.9) -11.3 (6.8)c -9.7 (6.8)b

PSSD Symptomscore, patients with 129 248 273 198 410 200baseline score > 0

Symptom score = 0, n (%)

Week 16 1 (0.8) 67 (27.0)a 45 (16.5)b 0 112 (27.3)a 30 (15.0)b

PSSD Sign score,patients with 129 248 274 198 411 201baseline score > 0

Sign score = 0, n (%)

Week 16 0 50 (20.2)a 32 (11.7)b 0 86 (20.9)a 21 (10.4)ba p < 0.001 for comparison between guselkumab and placebo.b comparisons between guselkumab and adalimumab were not performed.c p < 0.001 for comparison between guselkumab and placebo for major secondary endpoints.

Table 6: Summary of patient reported outcomes in the open-label phase in VOYAGE 1guselkumab adalimumab-guselkumab

Week 76 Week 156 Week 252 Week 76 Week 156 Week 252

DLQI score > 1 at445 420 374 264 255 235baseline, n

Patients with DLQI 337 308 272 198 190 1740/1 (75.7%) (73.3%) (72.7%) (75.0%) (74.5%) (74.0%)

PSSD Symptom

Score, patients347 327 297 227 218 200with baseline score> 0

Symptom 136 130 126 99 96 96score = 0, n (%) (39.2%) (39.8%) (42.4%) (43.6%) (44.0%) (48.0%)

PSSD Sign score,patients with 347 327 297 228 219 201baseline score > 0

Sign score = 0, n 102 94 98 71 69 76(%) (29.4%) (28.7%) (33.0%) (31.1%) (31.5%) (37.8%)

In VOYAGE 2, guselkumab patients had significantly greater improvement from baseline comparedto placebo in health-related quality of life, anxiety and depression, and work limitation measures at

Week 16, as measured by the 36-item Short Form (SF-36) health survey questionnaire, Hospital

Anxiety and Depression Scale (HADS), and Work Limitations Questionnaire (WLQ), respectively.

The improvements in SF-36, HADS and WLQ were all maintained through Week 48 and in theopen-label phase through Week 252 among patients randomised to maintenance therapy at Week 28.

NAVIGATE

The NAVIGATE study examined the efficacy of guselkumab in patients who had an inadequateresponse (i.e., who had not achieved a ‘cleared’ or ‘minimal’ response defined as IGA ≥ 2) toustekinumab at Week 16. All patients (N=871) received open-label ustekinumab (45 mg ≤100 kg and90 mg >100 kg) at Weeks 0 and 4. At Week 16, 268 patients with an IGA ≥ 2 score were randomisedto either continue ustekinumab treatment (N=133) q12w, or to initiate guselkumab treatment (N=135)at Weeks 16, 20, and q8w thereafter. Baseline characteristics for randomised patients were similar tothose observed in VOYAGE 1 and 2.

After randomisation, the primary endpoint was the number of post-randomisation visits between

Weeks 12 and 24 at which patients achieved an IGA score 0/1 and had ≥ 2 grade improvement.

Patients were examined at four week intervals for a total of four visits. Among patients whoinadequately responded to ustekinumab at the time of randomisation, significantly greaterimprovement of efficacy was observed in patients who switched to guselkumab treatment compared topatients who continued ustekinumab treatment. Between 12 and 24 weeks after randomisation,guselkumab patients achieved an IGA score 0/1 with ≥ 2 grade improvement twice as often asustekinumab patients (mean 1.5 vs 0.7 visits, respectively, p < 0.001). Additionally, at 12 weeks afterrandomisation a higher proportion of guselkumab patients compared to ustekinumab patients achievedan IGA score 0/1 and ≥ 2 grade improvement (31.1% vs. 14.3%, respectively; p = 0.001) and a

PASI 90 response (48% vs 23%, respectively, p < 0.001). Differences in response rates betweenguselkumab and ustekinumab treated patients were noted as early as 4 weeks after randomisation(11.1% and 9.0%, respectively) and reached a maximum 24 weeks after randomisation (see Figure 3).

No new safety findings were observed in patients who switched from ustekinumab to guselkumab.

Figure 3: Percent of patients who achieved an IGA Score of cleared (0) or minimal (1) and atleast a 2-grade improvement in IGA from week 0 through week 24 by visit afterrandomisation in NAVIGATE

ECLIPSE

Efficacy and safety of guselkumab were also investigated in a double-blind study compared tosecukinumab. Patients were randomised to receive guselkumab (N=534; 100 mg at Week 0, 4 and q8wthereafter), or secukinumab (N=514; 300 mg at Week 0, 1, 2, 3, 4, and q4w thereafter). The last dosewas at week 44 for both treatment groups.

Baseline disease characteristics were consistent with a population of moderate to severe plaquepsoriasis with a median BSA of 20%, a median PASI score of 18, and an IGA score of severe for 24%of patients.

Guselkumab was superior to secukinumab as measured by the primary endpoint of PASI 90 responseat Week 48 (84.5% versus 70.0%, p < 0.001). Comparative PASI response rates are presented in

Table 7.

Table 7: PASI response rates in ECLIPSE

Number of patients (%)guselkumab (N=534) secukinumab (N=514)

Primary Endpoint

PASI 90 response at Week 48 451 (84.5%) a 360 (70.0%)

Major Secondary Endpoints

PASI 75 response at both Week 12452 (84.6%) b 412 (80.2%)and Week 48

PASI 75 response at Week 12 477 (89.3%) c 471 (91.6%)

PASI 90 response at Week 12 369 (69.1%) c 391 (76.1%)

PASI 100 response at Week 48 311 (58.2%) c 249 (48.4%)a p < 0.001 for superiorityb p < 0.001 for non-inferiority, p=0.062 for superiorityc formal statistical testing was not performed

Guselkumab and secukinumab PASI 90 response rates through Week 48 are presented in Figure 4.

Figure 4: Percent of patients who achieved a PASI 90 response through week 48 by visit(Patients randomised at Week 0) in ECLIPSE

Psoriatic arthritis (PsA)

Guselkumab has been shown to improve signs and symptoms, physical function and health-relatedquality of life, and reduce the rate of progression of peripheral joint damage in adult patients withactive PsA.

DISCOVER 1 and DISCOVER 2

Two randomised, double-blind, placebo-controlled Phase III studies (DISCOVER 1 and

DISCOVER 2) evaluated the efficacy and safety of guselkumab versus placebo in adult patients withactive PsA (≥ 3 swollen and ≥ 3 tender joints, and a C-reactive protein (CRP) level of ≥ 0.3 mg/dL in

DISCOVER 1, and ≥ 5 swollen and ≥ 5 tender joints, and a CRP level of ≥ 0.6 mg/dL in

DISCOVER 2), despite conventional synthetic (cs)DMARD, apremilast, or nonsteroidalanti-inflammatory drug (NSAID) therapy. Patients in these studies had a diagnosis of PsA based onthe Classification criteria for Psoriatic Arthritis [CASPAR]) for a median duration of 4 years. Patientswith different subtypes of PsA were enrolled in both studies, including polyarticular arthritis with theabsence of rheumatoid nodules (40%), spondylitis with peripheral arthritis (30%), asymmetricperipheral arthritis (23%), distal interphalangeal involvement (7%) and arthritis mutilans (1%). Over65% and 42% of the patients had enthesitis and dactylitis at baseline, respectively, and over 75% ofpatients had ≥ 3% BSA psoriasis skin involvement. DISCOVER 1 and DISCOVER 2 evaluated 381and 739 patients, respectively, who received treatment with guselkumab 100 mg administered at

Weeks 0 and 4 followed by every 8 weeks (q8w) or guselkumab 100 mg q4w, or placebo. At Week24, placebo patients in both studies crossed over to receive guselkumab 100 mg q4w. Approximately58% of patients in both studies continued on stable doses of MTX (≤ 25 mg/week).

In both studies over 90% of patients had prior csDMARD use. In DISCOVER 1, 31% of patients hadpreviously received anti-TNFα treatment. In DISCOVER 2, all patients were naive to biologictherapy.

Signs and symptoms

Treatment with guselkumab resulted in significant improvements in the measures of disease activitycompared to placebo at Week 24. The primary endpoint in both studies was the percentage of patientswho achieved American College of Rheumatology (ACR) 20 response at Week 24. The key efficacyresults are shown in Table 8.

Table 8: Clinical responses in DISCOVER 1 and DISCOVER 2

DISCOVER 1 DISCOVER 2

Placebo guselkumab guselkumab Placebo guselkumab guselkumab(N=126) 100 mg q8w 100 mg q4w (N=246) 100 mg q8w 100 mg q4w(N=127) (N=128) (N=248) (N=245)

ACR 20 response

Week 16 25.4% 52.0% b 60.2% b 33.7% 55.2% g 55.9% c

Difference26.7 34.8 21.5 22.2from placebo - -(15.3, 38.1) (23.5, 46.0) (13.1, 30.0) (13.7, 30.7)(95% CI)

Week 24 22.2% 52.0% a 59.4% a 32.9% 64.1% a 63.7% a

Difference29.8 37.1 31.2 30.8from placebo - -(18.6, 41.1) (26.1, 48.2) (22.9, 39.5) (22.4, 39.1)(95% CI)

ACR 50 response

Week 16 12.7% 22.8% d 26.6% c 9.3% 28.6% g 20.8% c

Difference10.2 13.9 19.3 11.5from placebo - -(1.0, 19.3) (4.4, 23.4) (12.6, 25.9) (5.2, 17.7)(95% CI)

Week 24 8.7% 29.9% b 35.9% b 14.2% 31.5% g 33.1% c

Difference21.4 27.2 17.2 18.8from placebo - -(12.1, 30.7) (17.6, 36.8) (10.0, 24.4) (11.5, 26.1)(95% CI)

ACR 70 response

Week 24 5.6% 11.8% d 20.3% b 4.1% 18.5% g 13.1% c

Difference6.4 14.8 14.5 9.0from placebo - -(-0.3, 13.1) (6.9, 22.7) (9.1, 19.9) (4.1, 13.8)(95% CI)

DAS 28 (CRP) LSMean changei from baseline

Week 24 c -0.70 -1.43 b -1.61 b -0.97 -1.59 b -1.62 b

Difference -0.73 -0.91

- 0.61 -0.65from placebo - (-0.98, - (-1.16, - -(-0.80, -0.43) (-0.83, -0.47)(95% CI) 0.48) 0.66)

Minimal Disease Activity (MDA)

Week 24 11.1% 22.8% f 30.5% e 6.1% 25.0% e 18.8% e

Difference11.9 19.3 18.9 12.7from placebo - -(2.9, 20.9) (9.7, 28.9) (12.8, 25.0) (7.0, 18.4)(95% CI)

Patients with ≥ 3% BSA and IGA ≥ 2n=78 n=82 n=89 n=183 n=176 n=184

IGA response h

Week 24 15.4% 57.3% b 75.3% b 19.1% 70.5% b 68.5% b

Difference42.0 60.0 50.9 49.8from placebo - -(28.9, 55.1) (48.3, 71.8) (42.2, 59.7) (41.2, 58.4)(95% CI)

PASI 90 response

Week 16 10.3% 45.1% e 52.8% e 8.2% 55.1% e 53.8% e

Difference 34.9 42.6 46.6 45.6from placebo - (22.2, 47.6) (30.5, 54.8) - (38.4, 54.8) (37.6, 53.6)(95% CI)

Week 24 11.5% 50.0% e 62.9% e 9.8% 68.8% e 60.9% e

Difference 38.6 51.7 51.3from placebo - (25.8, 51.4) (39.7, 63.7) - 58.6 (43.2, 59.3)(95% CI) (50.6, 66.6)a p < 0.001 (primary endpoint)b p < 0.001 (major secondary endpoint)c p = 0.006 (major secondary endpoint)d not statistically significant p=0.086 (major secondary endpoint)e nominal p < 0.001f nominal p = 0.012g not formally tested in the hierarchical testing procedure, nominal p < 0.001 (major secondary endpoint)h defined as a IGA response of 0 (cleared) or 1 (minimal) and ≥ 2-grade reduction from baseline in the IGA psoriasisscorei LSmean change = least squares mean change

Clinical response was maintained up to Week 52 as assessed by ACR 20/50/70, DAS 28 (CRP),

MDA, IGA and PASI 90 response rates in DISCOVER 1 and DISCOVER 2 (see Table 9).

Table 9: Clinical responses in DISCOVER 1 and DISCOVER 2 at week 52a

DISCOVER 1 DISCOVER 2guselkumab guselkumab guselkumab guselkumab100 mg q8w 100 mg q4w 100 mg q8w 100 mg q4w

ACR 20

Nb 112 124 234 228% Response 67.9% 75.8% 79.1% 75.9%

ACR 50

Nb 113 124 234 228% Response 43.4% 55.6% 51.3% 49.1%

ACR 70

Nb 114 124 234 228% Response 28.9% 29.8% 29.5% 28.1%

DAS 28 (CRP) change from baseline

Nc 112 123 234 227

Mean (SD) -2.03 (1.250) -1.99 (1.062) -2.08 (1.121) -2.11 (1.128)

MDA

Nb 112 124 234 228% Response 33.9% 40.3% 32.9% 36.8%

Patients with ≥ 3% BSA and IGA ≥ 2 at baseline

IGA Response

Nb 75 88 170 173% Response 69.3% 83.0% 77.1% 84.4%

PASI 90

Nb 75 88 170 173% Response 66.7% 76.1% 77.1% 81.5%a There was no placebo arm beyond Week 24.b Evaluable patients with an observed response status.c Patients have an observed change from baseline.

Clinical response was maintained up to Week 100 as assessed by ACR 20/50/70, DAS 28 (CRP),

MDA, IGA and PASI 90 response rates in DISCOVER 2 (see Table 10).

Table 10: Clinical responses in DISCOVER 2 at week 100aguselkumab guselkumab100 mg q8w 100 mg q4w

ACR 20

Nb 223 219% Response 82.1% 84.9%

ACR 50

Nb 224 220% Response 60.7% 62.3%

ACR 70

Nb 224 220% Response 39.3% 38.6%

DAS 28 (CRP) change from baseline

Nc 223 219

Mean (SD) -2.37 (1.215) -2.36 (1.120)

MDA

Nb 224 220% Response 44.6% 42.7%

Patients with ≥ 3% BSA and IGA ≥ 2 at baseline

IGA Response

Nb 165 170% Response 76.4% 82.4%

PASI 90

Nb 164 170% Response 75.0% 80.0%a There was no placebo arm beyond Week 24.b Evaluable patients with an observed response status.c Patients have an observed change from baseline.

Response over time

In DISCOVER 2, a greater ACR 20 response was observed in both guselkumab groups compared toplacebo as early as Week 4 and the treatment difference continued to increase over time through

Week 24 (Figure 5).

Figure 5: ACR 20 response by visit through week 24 in DISCOVER 2

In DISCOVER 2, for patients receiving continuous guselkumab treatment at week 24, ACR 20response was maintained from Week 24 to Week 52 (see Figure 6). For patients receiving continuousguselkumab treatment at week 52, ACR 20 response was maintained from Week 52 to Week 100 (see

Figure 7).

Figure 6: ACR 20 response by visit from Figure 7: ACR 20 response by visit fromweek 24 through week 52 in week 52 through week 100 in

DISCOVER 2 DISCOVER 2

Responses observed in the guselkumab groups were similar regardless of concomitant csDMARD use,including MTX (DISCOVER 1 and 2). Additionally, examination of age, gender, race, body weight,and previous csDMARD use (DISCOVER 1 and 2) and previous anti-TNFα use (DISCOVER 1), didnot identify differences in response to guselkumab among these subgroups.

In DISCOVER 1 and 2, improvements were shown in all components of the ACR scores includingpatient assessment of pain. At Week 24 in both studies, the proportion of patients achieving a modified

PsA response criteria (PsARC) response was greater in the guselkumab groups compared to placebo.

PsARC responses were maintained from Week 24 to Week 52 in DISCOVER 1 and Week 100 in

DISCOVER 2.

Dactylitis and enthesitis were assessed based on pooled data from DISCOVER 1 and 2. At Week 24,among patients with dactylitis at baseline, the proportion of patients with dactylitis resolution wasgreater in the guselkumab q8w group (59.4%, nominal p < 0.001) and q4w group (63.5%, p = 0.006)compared to placebo (42.2%). At Week 24, among patients with enthesitis at baseline, the proportionof patients with enthesitis resolution was greater in the guselkumab q8w group (49.6%, nominalp < 0.001) and q4w group (44.9%, p = 0.006) compared to placebo (29.4%). At Week 52, theproportions of patients with dactylitis resolution (81.2% in q8w group and 80.4% in q4w group) andenthesitis resolution (62.7% in q8w group and 60.9% in q4w group) were maintained. In DISCOVER2, among patients with dactylitis and enthesitis at baseline, the proportion of patients with dactylitisresolution (91.1% in q8w group and 82.9% in q4w group) and enthesitis resolution (77.5% in q8wgroup and 67.7% in q4w group) were maintained at Week 100.

In DISCOVER 1 and 2, patients treated with guselkumab who had spondylitis with peripheral arthritisas their primary presentation, demonstrated greater improvement from baseline in Bath Ankylosing

Spondylitis Disease Activity Index (BASDAI) compared to placebo at Week 24. Improvement in

BASDAI was maintained from Week 24 to Week 52 in DISCOVER 1 and Week 100 in DISCOVER2.

In DISCOVER 2, inhibition of structural damage progression was measured radiographically andexpressed as the mean change from baseline in the total modified van der Heijde-Sharp (vdH-S) score.

At Week 24, the guselkumab q4w group demonstrated statistically significantly less radiographicprogression and the guselkumab q8w group showed numerically less progression than placebo(Table 11). The observed benefit with the guselkumab q4w dosing regimen on inhibition ofradiographic progression (i.e., smaller mean change from baseline in total modified vdH-S score in theq4w group versus placebo) was most pronounced in patients with both a high C-reactive protein valueand high number of joints with erosions at baseline.

Table 11: Change from baseline in total modified vdH-S score at week 24 in DISCOVER 2

N LSMean changec (95% CId) from baseline in modified vdH-

S score at Week 24

Placebo 246 0.95 (0.61, 1.29)guselkumab 100 mg q8w 248 0.52 a (0.18, 0.86)guselkumab 100 mg q4w 245 0.29 b (-0.05, 0.63)a not statistically significant p = 0.068 (major secondary endpoint).b p = 0.006 (major secondary endpoint).c LSmean change = least squares mean change.d CI = confidence interval.

At Week 52 and Week 100, the mean change from baseline in total modified vdH-S was similar in theguselkumab q8w and q4w groups (Table 12).

Table 12: Change from baseline in total modified vdH-S score at week 52 and week 100 in

DISCOVER 2

Na Mean change (SDb) from baseline in total modified vdH-Sscore

Week 52guselkumab 100 mg q8w 235 0.97 (3.623)guselkumab 100 mg q4w 229 1.07 (3.843)

Week 100guselkumab 100 mg q8w 216 1.50 (4.393)guselkumab 100 mg q4w 211 1.68 (7.018)a Evaluable patients have observed change for the specified time periodb SD = standard deviation

Note: no placebo group beyond Week 24

In DISCOVER 1 and 2, guselkumab treated patients showed significant improvement (p < 0.001) inphysical function compared to placebo as assessed by the Health Assessment Questionnaire-Disability

Index (HAQ-DI) at Week 24. Improvements in HAQ-DI were maintained from Week 24 to Week 52in DISCOVER 1 and Week 100 in DISCOVER 2.

A significantly greater improvement from baseline in the SF-36 Physical Component Summary (PCS)score was observed in guselkumab treated patients compared to placebo at Week 24 in DISCOVER 1(p < 0.001 for both dose groups) and DISCOVER 2 (p = 0.006 for q4w group). At Week 24, a greaterincrease from baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) scorewas observed in guselkumab treated patients compared to placebo in both studies. In DISCOVER 2,greater improvements in health-related quality of life as measured by the Dermatology Life Quality

Index (DLQI) were observed in guselkumab treated patients compared to placebo at Week 24.

Improvements in SF-36 PCS, FACIT-F and DLQI scores were maintained from Week 24 to Week 52in DISCOVER 1 and Week 100 in DISCOVER 2.

The efficacy and safety of guselkumab were evaluated in two Phase III multicentre, randomised,double-blind, placebo-controlled studies (QUASAR induction study and QUASAR maintenancestudy) in adult patients with moderately to severely active ulcerative colitis who had an inadequateresponse, loss of response, or intolerance to corticosteroids, conventional immunomodulators (AZA,6-MP), biologic therapy (TNF blockers, vedolizumab), and/or a Janus kinase (JAK) inhibitor. Inaddition, efficacy and safety of guselkumab were evaluated in a randomised, double-blind, placebo-controlled, Phase IIb induction dose-finding study (QUASAR induction dose-ranging study) thatenrolled a similar ulcerative colitis patient population as the Phase III induction study.

Disease activity was assessed by the modified Mayo score (mMS), a 3-component Mayo score (0-9)which consists of the sum of the following subscores (0 to 3 for each subscore): stool frequency (SFS),rectal bleeding (RBS), and findings on centrally reviewed endoscopy (ES). Moderately to severelyactive ulcerative colitis was defined as a mMS between 5 and 9, a RBS ≥ 1, and an ES of 2 (defined bymarked erythema, absent vascular pattern, friability, and/or erosions) or an ES of 3 (defined byspontaneous bleeding and ulceration).

Induction study: QUASAR IS

In the induction study QUASAR IS, patients were randomised in a 3:2 ratio to receive eitherguselkumab 200 mg or placebo by intravenous infusion at Week 0, Week 4, and Week 8. A total of701 patients were evaluated. At baseline the median mMS was 7, with 35.5% of patients having abaseline mMS of 5 to 6 and 64.5% having a mMS of 7 to 9, and 67.9% of patients with a baseline ESof 3. The median age was 39 years (ranging from 18 to 79 years); 43.1% were female; and 72.5%identified as White, 21.4% as Asian and 1% as Black.

Enrolled patients were permitted to use stable doses of oral aminosalicylates, MTX, 6-MP, AZAand/or oral corticosteroids. At baseline, 72.5% of patients were receiving aminosalicylates, 20.8% ofpatients were receiving immunomodulators (MTX, 6-MP, or AZA), and 43.1% of patients werereceiving corticosteroids. Concomitant biologic therapies or JAK inhibitors were not permitted.

A total of 49.1% of patients had previously failed at least one biologic therapy, and/or JAK inhibitor.

Of these patients, 87.5%, 54.1% and 18% had previously failed a TNF blocker, vedolizumab or a JAKinhibitor, respectively, and 47.4% had failed treatment with 2 or more of these therapies. A total of48.4% of patients were biologic and JAK inhibitor naïve, and 2.6% had previously received but hadnot failed a biologic or JAK inhibitor.

The primary endpoint was clinical remission as defined by the mMS at Week 12. Secondary endpointsat Week 12 included symptomatic remission, endoscopic healing, clinical response, histologicendoscopic mucosal healing, fatigue response and IBDQ remission (Table 13).

Significantly greater proportions of patients were in clinical remission at Week 12 in the guselkumabtreated group compared to the placebo group.

Table 13: Proportion of patients meeting efficacy endpoints at Week 12 in QUASAR IS

Endpoint Placebo Guselkumab Treatment% 200 mg intravenous Differenceinductiona (95% CI)%

Clinical remissionb

Total population 8% (N=280) 23% (N=421) 15% (10%, 20%)c

Biologic and JAK inhibitor 12% (N=137) 32% (N=202) 20% (12%, 28%)naïved

Prior biologic and/or JAK 4% (N=136) 13% (N=208) 9% (3%, 14%)inhibitor failuree

Symptomatic remissionf

Total population 21% (N=280) 50% (N=421) 29% (23%, 36%)c

Biologic and JAK inhibitor 26% (N=137) 60% (N=202) 34% (24%, 44%)naïved

Prior biologic and/or JAK 14% (N=136) 38% (N=208) 24% (16%, 33%)inhibitor failuree

Endoscopic healingg

Total population 11% (N=280) 27% (N=421) 16% (10%, 21%)c

Biologic and JAK inhibitor 17% (N=137) 38% (N=202) 21% (12%, 30%)naïved

Prior biologic and/or JAK 5% (N=136) 15% (N=208) 10% (4%, 16%)inhibitor failuree

Clinical responseh

Total population 28% (N=280) 62% (N=421) 34% (27%, 41%)c

Biologic and JAK inhibitor 35% (N=137) 71% (N=202) 36% (26%, 46%)naïved

Prior biologic and/or JAK 20% (N=136) 51% (N=208) 32% (22%, 41%)inhibitor failuree

Histologic endoscopic mucosal healingi

Total Population 8% (N=280) 24% (N=421) 16% (11%, 21%)c

Biologic and JAK inhibitor 11% (N=137) 33% (N=202) 22% (13%, 30%)naïved

Prior biologic and/or JAK 4% (N=136) 13% (N=208) 9% (3%, 15%)inhibitor failuree

Fatigue responsej

Total population 21% (N=280) 41% (N=421) 20% (13%, 26%)c

Biologic and JAK inhibitor 29% (N=137) 42% (N=202) 12% (2%, 23%)naïved

Prior biologic and/or JAK 13% (N=136) 38% (N=208) 25% (17%, 34%)inhibitor failuree

IBDQ remissionk

Total population 30% (N=280) 51% (N=421) 22% (15%, 29%)c

Biologic and JAK inhibitor 34% (N=137) 62% (N=202) 28% (18%, 38%)naïved

Prior biologic and/or JAK 24% (N=136) 39% (N=208) 15% (5%, 25%)inhibitor failureea Guselkumab 200 mg as an intravenous induction at Week 0, Week 4, and Week 8.b A stool frequency subscore of 0 or 1 and not increased from baseline, a rectal bleeding subscore of 0, and an endoscopy subscore of 0or 1 with no friability.c p < 0.001, adjusted treatment difference (95% CI) based on Cochran-Mantel-Haenszel method (adjusted for stratification factors:

biologic and/or JAK-inhibitor failure status and concomitant use of corticosteroids at baseline).d An additional 7 patients in the placebo group and 11 patients in the guselkumab group were previously exposed to but did not fail abiologic or JAK inhibitor.e Includes inadequate response, loss of response, or intolerance to biologic therapy (TNF blockers, vedolizumab) and/or a Janus kinase(JAK) inhibitor for ulcerative colitis.f A stool frequency subscore of 0 or 1 and not increased from induction baseline, and a rectal bleeding subscore of 0.g An endoscopy subscore of 0 or 1 with no friability.h Decrease from induction baseline in the modified Mayo score by ≥ 30% and ≥ 2 points, with either a ≥ 1-point decrease frombaseline in the rectal bleeding subscore or a rectal bleeding subscore of 0 or 1.i A combination of histologic healing [neutrophil infiltration in < 5% of crypts, no crypt destruction, and no erosions, ulcerations orgranulation tissue according to the Geboes grading system] and endoscopic healing as defined above.j Fatigue was assessed using the PROMIS-Fatigue Short form 7a. Fatigue response was defined as a ≥ 7-point improvement frombaseline which is considered clinically meaningful.k Total Inflammatory Bowel Disease Questionnaire score ≥ 170.

QUASAR IS and QUASAR induction dose-ranging study also enrolled 48 patients with a baselinemMS of 4, including an ES of 2 or 3 and a RBS ≥ 1. In patients with a baseline mMS of 4,guselkumab efficacy relative to placebo, as measured by clinical remission, clinical response, andendoscopic healing at Week 12, was consistent with the total moderately to severely active ulcerativecolitis population.

Rectal bleeding and stool frequency subscores

Decreases in rectal bleeding and stool frequency subscores were observed as early as Week 2 inpatients treated with guselkumab and continued to decrease through Week 12.

Maintenance study: QUASAR MS

The QUASAR MS evaluated 568 patients who achieved clinical response at 12 weeks following theintravenous administration of guselkumab in either QUASAR IS or from the QUASAR inductiondose-ranging study. In the QUASAR MS, these patients were randomised to receive a subcutaneousmaintenance regimen of either guselkumab 100 mg every 8 weeks, guselkumab 200 mg every 4 weeksor placebo for 44 weeks.

The primary endpoint was clinical remission as defined by mMS at Week 44. Secondary endpoints at

Week 44 included but were not limited to symptomatic remission, endoscopic healing, corticosteroid-free clinical remission, histologic endoscopic mucosal healing, fatigue response and IBDQ remission(Table 14).

Significantly greater proportions of patients were in clinical remission at Week 44 in both guselkumabtreated groups compared to the placebo.

Table 14: Proportion of patients meeting efficacy endpoints at Week 44 in QUASAR MS

Endpoint Placebo Guselkumab Guselkumab Treatment Difference% 100 mg q8w 200 mg q4w (95% CI)subcutaneous subcutaneous Guselkumab Guselkumabinjectiona injectionb 100 mg 200 mg% %

Clinical remissionc

Total populationd 19% (N=190) 45% (N=188) 50% (N=190) 25% 30%(16%, 34%)e (21%, 38%)e

Biologic and JAK- 26% (N=108) 50% (N=105) 58% (N=96) 24% 29%inhibitor naïvef (12%, 36%) (17%, 41%)

Prior biologic and/or 8% (N=75) 40% (N=77) 40% (N=88)30% 32%

JAK-inhibitorg (19%, 42%) (21%, 44%)failure

Symptomatic remissionh

Total populationd 37% (N=190) 70% (N=188) 69% (N=190) 32% 31%(23%, 41%)e (21%, 40%)e

Biologic and JAK- 46% (N=108) 74% (N=105) 76% (N=96) 28% 28%inhibitor naïvef (15%, 40%) (15%, 41%)

Prior biologic and/or 24% (N=75) 65% (N=77) 60% (N=88)39% 37%

JAK-inhibitorg (26%, 52%) (23%, 50%)failure

Corticosteroid-free clinical remissioni

Total populationd 18% (N=190) 45% (N=188) 49% (N=190) 26% 29%(17%, 34%)e (20%, 38%)e

Biologic and JAK- 26% (N=108) 50% (N=105) 56% (N=96) 24% 27%inhibitor naïvef (12%, 36%) (14%, 39%)

Prior biologic and/or 7% (N=75) 40% (N=77) 40% (N=88)32% 34%

JAK-inhibitorg (21%, 43%) (23%, 45%)failure

Endoscopic healingj

Total populationd 19% (N=190) 49% (N=188) 52% (N=190) 30% 31%(21%, 38%)e (22%, 40%)e

Biologic and JAK- 26% (N=108) 53% (N=105) 59% (N=96) 27% 30%inhibitor naïvef (15%, 40%) (18%, 42%)

Prior biologic and/or 8% (N=75) 45% (N=77) 42% (N=88)36% 35%

JAK-inhibitor failureg (24%, 48%) (23%, 46%)

Histologic endoscopic mucosal healingk

Total populationd 17% (N=190) 44% (N=188) 48% (N=190) 26% 30%(17%, 34%)e (21%, 38%)e

Biologic and JAK- 23% (N=108) 50% (N=105) 56% (N=96) 26% 30%inhibitor naïvef (14%, 38%) (17%, 42%)

Prior biologic and/or 8% (N=75) 38% (N=77) 39% (N=88)28% 31%

JAK-inhibitorg (16%, 39%) (20%, 43%)failure

Clinical responsel

Total populationd 43% (N=190) 78% (N=188) 75% (N=190) 34% 31%(25%, 43%)e (21%, 40%)e

Biologic and JAK- 54% (N=108) 83% (N=105) 81% (N=96) 29% 26%inhibitor naïvef (17%, 41%) (14%, 39%)

Prior biologic and/or 28% (N=75) 70% (N=77) 67% (N=88)41% 39%

JAK-inhibitorg (27%, 54%) (26%, 53%)failure

Maintenance of Clinical Remission at Week 44 in patients who achieved clinical remission 12 weeksafter induction

Total populationq 34% (N=59) 61% (N=66) 72% (N=69) 26% 38%(9%, 43%)m (23%, 54%)e

Biologic and JAK- 34% (N=41) 65% (N=43) 79% (N=48) 31% 45%inhibitor naïver (9%, 51%) (25%, 62%)

Prior biologic and/or 27% (N=15) 60% (N=20) 56% (N=18)33% 29%

JAK-inhibitorg (-1%, 62%) (-6%, 59%)failure

Endoscopic normalisationn

Total populationd 15% (N=190) 35% (N=188) 34% (N=190) 18% 17%(10%, 27%)e (9%, 25%)e

Biologic and JAK- 20% (N=108) 38% (N=105) 42% (N=96) 17% 17%inhibitor naïve f (6%, 29%) (6%, 29%)

Prior biologic and/or 8% (N=75) 31% (N=77) 24% (N=88)21% 16%

JAK-inhibitorg (10%, 33%) (6%, 26%)failure

Fatigue responseo

Total population d 29% (N=190) 51% (N=188) 43% (N=190) 20% 13%(11%, 29%)e (3%, 22%)m

Biologic and JAK- 36% (N=108) 51% (N=105) 53% (N=96) 15% 16%inhibitor naïvef (2%, 28%) (3%, 29%)

Prior biologic and/or 19% (N=75) 47% (N=77) 32% (N=88)27% 13%

JAK-inhibitorg (13%, 40%) (1%, 26%)failure

IBDQ remissionp

Total populationd 37% (N=190) 64% (N=188) 64% (N=190) 26% 26%(17%, 36%)e (16%, 35%)e

Biologic and JAK- 49% (N=108) 68% (N=105) 74% (N=96) 19% 24%inhibitor naïve f (6%, 32%) (11%, 37%)

Prior biologic and/or 19% (N=75) 58% (N=77) 53% (N=88)38% 35%

JAK-inhibitorg (26%, 50%) (23%, 48%)failurea Guselkumab 100 mg as a subcutaneous injection every 8 weeks after the induction regimen.b Guselkumab 200 mg as a subcutaneous injection every 4 weeks after the induction regimen.c A stool frequency subscore of 0 or 1 and not increased from baseline, a rectal bleeding subscore of 0, and an endoscopy subscore of 0or 1 with no friability.d Patients who achieved clinical response 12 weeks following the intravenous administration of guselkumab in either QUASARinduction study or QUASAR induction dose-ranging study.e p <0.001, adjusted treatment difference (95% CI) based on Cochran-Mantel-Haenszel method adjusted for randomisationstratification factors.f An additional 7 patients in the placebo group, 6 patients in the guselkumab 100 mg group, and 6 patients in the guselkumab 200 mggroup were previously exposed to but did not fail a biologic or JAK inhibitor.g Includes inadequate response, loss of response, or intolerance to biologic therapy (TNF blockers, vedolizumab) and/or a Janus kinase[JAK] inhibitor for ulcerative colitis.h A stool frequency subscore of 0 or 1 and not increased from induction baseline, and a rectal bleeding subscore of 0.i Not requiring any treatment with corticosteroids for at least 8 weeks prior to Week 44 and also meeting the criteria for clinicalremission at Week 44.j An endoscopy subscore of 0 or 1 with no friability.k A combination of histologic healing [neutrophil infiltration in < 5% of crypts, no crypt destruction, and no erosions, ulcerations orgranulation tissue according to the Geboes grading system] and endoscopic healing as defined above.l Decrease from induction baseline in the modified Mayo score by ≥ 30% and ≥ 2 points, with either a ≥ 1-point decrease frombaseline in the rectal bleeding subscore or a rectal bleeding subscore of 0 or 1.m p < 0.01, adjusted treatment difference (95% CI) based on Cochran-Mantel-Haenszel method adjusted for randomisationstratification factorsn An endoscopy subscore of 0.o Fatigue was assessed using the PROMIS-Fatigue Short form 7a. Fatigue response was defined as a ≥ 7-point improvement frominduction baseline which is considered clinically meaningful.p Total Inflammatory Bowel Disease Questionnaire score ≥ 170.q Subjects who achieved clinical remission 12 weeks following intravenous administration of guselkumab in either QUASARinduction study or QUASAR induction dose-ranging study.r An additional 3 patients in the placebo group, 3 patients in the guselkumab 100 mg group, and 3 patients in the guselkumab 200 mggroup were previously exposed to but did not fail a biologic or JAK inhibitor.

In QUASAR IS and QUASAR MS, the efficacy and safety of guselkumab was consistentlydemonstrated regardless of age, sex, race, body weight, and previous treatment with a biologic therapyor JAK inhibitor.

In QUASAR MS, patients with high inflammatory burden after completion of induction dosingderived additional benefit from guselkumab 200 mg subcutaneous q4w compared to 100 mgsubcutaneous q8w dosing. Clinically meaningful numerical differences of > 15% were observedbetween the two guselkumab dose groups among patients with a CRP level of >3 mg/L aftercompletion of induction dosing for the following endpoints at Week 44: clinical remission (48%200 mg q4w vs. 30% 100 mg q8w), maintenance of clinical remission (88% 200 mg q4w vs. 50%100 mg q8w), corticosteroid-free clinical remission (46% 200 mg q4w vs. 30% 100 mg q8w),endoscopic healing (52% 200 mg q4w vs. 35% 100 mg q8w), and histologic-endoscopic mucosalhealing (46% 200 mg q4w vs. 29% 100 mg q8w).

QUASAR MS enrolled 31 patients with an induction baseline mMS of 4, including an ES of 2 or 3and a RBS ≥ 1 who achieved clinical response 12 weeks following the intravenous administration ofguselkumab in QUASAR IS or QUASAR induction dose-ranging study. In these patients, guselkumabefficacy relative to placebo as measured by clinical remission, clinical response, and endoscopichealing at Week 44 was consistent with the total population.

Symptomatic remission over time

In QUASAR MS symptomatic remission defined as stool frequency subscore of 0 or 1 and notincreased from induction baseline, and a rectal bleeding subscore of 0 was sustained through Week 44in both guselkumab treatment groups, while a decline was observed in the placebo group (Figure 8):

Figure 8: Proportion of patients in symptomatic remission through Week 44 in QUASAR MS

Week 24 responders to guselkumab extended treatment

Guselkumab treated patients who were not in clinical response at induction Week 12, receivedguselkumab 200 mg subcutaneous at Weeks 12, 16 and 20. In QUASAR IS, 66/120 (55%)guselkumab treated patients who were not in clinical response at induction Week 12 achieved clinicalresponse at Week 24. Week 24 responders to guselkumab entered QUASAR MS and receivedguselkumab 200 mg subcutaneous every 4 weeks. At Week 44 of QUASAR MS, 83/123 (67%) ofthese patients maintained clinical response and 37/123 (30%) achieved clinical remission.

Recapture of efficacy after loss of response to guselkumab

Nineteen patients receiving guselkumab 100 mg subcutaneous q8w who experienced a first loss ofresponse (10%) between Week 8 and 32 of QUASAR MS received blinded guselkumab dosing with200 mg guselkumab subcutaneous q4w and 11 of these patients (58%) achieved symptomatic responseand 5 patients (26%) achieved symptomatic remission after 12 weeks.

Histologic and endoscopic assessment

Histologic remission was defined as a Geboes histologic score ≤ 2 B.0 (absence of neutrophils fromthe mucosa [both lamina propria and epithelium], no crypt destruction, and no erosions, ulcerations orgranulation tissue according to the Geboes grading system). In QUASAR IS, histologic remission at

Week 12 was achieved in 40% of patients treated with guselkumab and 19% of patients in the placebogroup. In QUASAR MS, histologic remission at Week 44 was achieved in 59% and 61% of patientstreated with guselkumab 100 mg subcutaneous q8w and guselkumab 200 mg subcutaneous q4w and27% of patients in the placebo group.

Normalisation of the endoscopic appearance of the mucosa was defined as ES of 0. In QUASAR IS,endoscopic normalisation at Week 12 was achieved in 15% of patients treated with guselkumab and5% of patients in the placebo group.

Composite histologic-endoscopic mucosal outcomes

Combined symptomatic remission, endoscopic normalisation, histologic remission, and faecalcalprotectin ≤ 250 mg/kg at Week 44 was achieved by a greater proportion of patients treated withguselkumab 100 mg subcutaneous q8w or 200 mg subcutaneous q4w compared to placebo (22% and28% vs 9%, respectively).

At Week 12 of QUASAR IS, patients receiving guselkumab showed greater and clinically meaningfulimprovements from baseline when compared with placebo in inflammatory bowel disease (IBD)-specific quality of life assessed by IBDQ total score, and all IBDQ domain scores (bowel symptomsincluding abdominal pain and bowel urgency, systemic function, emotional function, and socialfunction). These improvements were maintained in guselkumab-treated patients in QUASAR MSthrough Week 44.

Ulcerative colitis related hospitalisations

Through Week 12 of QUASAR IS, lower proportions of patients in the guselkumab group comparedwith the placebo group had ulcerative colitis-related hospitalisations (1.9%, 8/421 vs. 5.4%, 15/280).

The efficacy and safety of guselkumab were evaluated in three Phase III clinical studies in adultpatients with moderately to severely active Crohn’s disease who had an inadequate response, loss ofresponse or intolerance to either oral corticosteroids, conventional immunomodulators (AZA, 6-MP,

MTX) and/or biologic therapy (TNF blocker or vedolizumab): two identically designed 48-Weekmulticentre, randomised, double-blind, placebo- and active-controlled (ustekinumab), parallel groupstudies (GALAXI 2 and GALAXI 3) and one 24-Week multicentre, randomised, double-blind,placebo-controlled, parallel group study (GRAVITI). All three studies had a treat-through studydesign: patients randomised to guselkumab (or ustekinumab for GALAXI 2 and GALAXI 3)maintained that treatment assignment for the duration of the study.

GALAXI 2 and GALAXI 3

In the Phase III studies GALAXI 2 and GALAXI 3, moderately to severely active Crohn’s disease wasdefined as a Crohn’s Disease Activity Index [CDAI] score of ≥ 220 and ≤ 450 and a Simple

Endoscopic Score for CD (SES-CD) of ≥ 6 (or ≥ 4 for patients with isolated ileal disease). Additionalcriteria for GALAXI 2/3 included a mean daily stool frequency (SF) > 3 or mean daily abdominal painscore (AP) > 1.

In GALAXI 2 and GALAXI 3 studies, patients were randomised in a 2:2:2:1 ratio to receiveguselkumab 200 mg intravenous induction at Weeks 0, 4 and 8 followed by guselkumab 200 mgsubcutaneous q4w maintenance; or guselkumab 200 mg intravenous induction at Weeks 0, 4 and 8,followed by guselkumab 100 mg subcutaneous q8w maintenance; or ustekinumab approximately6 mg/kg intravenous induction at Week 0 followed by ustekinumab 90 mg subcutaneous q8wmaintenance; or placebo. Placebo non-responders received ustekinumab starting at Week 12.

A total of 1021 patients were evaluated in GALAXI 2 (n=508) and GALAXI 3 (n=513). The medianage was 34 years (ranging from 18 to 83 years), 57.6% were male; and 74.3% identified as White,21.3% as Asian and 1.5% as Black.

In GALAXI 2, 52.8% of patients had previously failed treatment with at least one biologic therapy(50.6% were intolerant or failed at least 1 prior anti-TNFα therapy, 7.5% were intolerant or failed priorvedolizumab therapy), 41.9% were biologic naïve, and 5.3% had previously received but had notfailed a biologic. At baseline, 37.4% of the patients were receiving oral corticosteroids and 29.9% ofthe patients were receiving conventional immunomodulators.

In GALAXI 3, 51.9% of patients had previously failed treatment with at least one biologic therapy(50.3% were intolerant or failed at least 1 prior anti-TNFα therapy, 9.6% were intolerant or failed priorvedolizumab therapy), 41.5% were biologic naïve, and 6.6% had previously received but had notfailed a biologic. At baseline, 36.1% of the patients were receiving oral corticosteroids and 30.2% ofthe patients were receiving conventional immunomodulators.

The results of the co-primary and major secondary endpoints compared to placebo in GALAXI 2 and

GALAXI 3 are presented in Tables 15 (Week 12) and 16 (Week 48). The results of the majorsecondary endpoints at Week 48 compared to ustekinumab are presented in Tables 17 and 18.

Table 15: Proportion of patients meeting co-primary and major secondary efficacyendpoints with guselkumab versus placebo at Week 12 in GALAXI 2 and

GALAXI 3

GALAXI 2 GALAXI 3

Placebo Guselkumab Placebo Guselkumab% intravenous % intravenousinductiona inductiona% %

Co-primary efficacy endpoints

Clinical remissionb at Week 12

Total population 22% (N=76) 47%i (N=289) 15% (N=72) 47%i (N=293)

Biologic naïvec 18% (N=34) 50% (N=121) 15% (N=27) 50% (N=123)

Prior biologic failured 23% (N=39) 45% (N=150) 15% (N=39) 47% (N=150)

Endoscopic responsee at Week 12

Total population 11% (N=76) 38%i (N=289) 14% (N=72) 36%i (N=293)

Biologic naïvec 15% (N=34) 51% (N=121) 22% (N=27) 41% (N=123)

Prior biologic failured 5% (N=39) 27% (N=150) 8% (N=39) 31% (N=150)

Major secondary efficacy endpoints

PRO-2 remissionf at Week 12

Total population 21% (N=76) 43%i (N=289) 14% (N=72) 42%i(N=293)

Biologic naïvec 24% (N=34) 43% (N=121) 15% (N=27) 47% (N=123)

Prior biologic failured 13% (N=39) 41% (N=150) 13% (N=39) 39% (N=150)

Fatigue responseg at Week 12

Total population 29% (N=76) 45%j (N=289) 18% (N=72) 43%i(N=293)

Biologic naïvec 32% (N=34) 48% (N=121) 19% (N=27) 46% (N=123)

Prior biologic failured 26% (N=39) 41% (N=150) 18% (N=39) 43% (N=150)

Endoscopic remissionh at Week 12

Total population 1% (N=76) 15% (N=289) 8% (N=72) 16% (N=293)

Biologic naïvec 3% (N=34) 22% (N=121) 19% (N=27) 25% (N=123)

Prior biologic failured 0% (N=39) 9% (N=150) 0% (N=39) 9% (N=150)a Guselkumab 200 mg intravenous induction at Week 0, Week 4 and Week 8 - Two guselkumab treatment groups werecombined for this column as patients received the same intravenous induction dose regimen prior to Week 12.

b Clinical remission is defined as CDAI score < 150.c An additional 9 patients in the placebo group and 38 patients in the guselkumab 200 mg intravenous group werepreviously exposed to but did not fail a biological therapy.d Includes inadequate response, loss of response, or intolerance to biologic therapy (TNF blockers or vedolizumab) for

Crohn’s disease.e Endoscopic response is defined as ≥ 50% improvement from baseline in SES-CD score or SES-CD Score ≤ 2.f PRO-2 remission is defined as AP mean daily score at or below 1 and SF mean daily score at or below 3, and noworsening of AP or SF from baseline.g Fatigue response is defined as improvement of ≥ 7 points in PROMIS Fatigue Short Form 7a.h Endoscopic remission is defined as SES-CD Score ≤ 2.i p < 0.001j p < 0.05

Table 16: Proportion of patients meeting major secondary efficacy endpoints withguselkumab versus placebo at Week 48 in GALAXI 2 and GALAXI 3

GALAXI 2 GALAXI 3

Placebo Guselkumab Guselkumab Placebo Guselkumab Guselkumabintravenous intravenous (N=72) intravenous intravenousinduction→ induction→ induction→ induction→100 mg q8w 200 mg q4w 100 mg q8w 200 mg q4wsubcutaneous subcutaneous subcutaneous subcutaneousinjectiona injectionb injectiona injectionb

Corticosteroid-free clinical remissionc at Week 48f

Total 12% 45%e 51%e 14% 44%e 48%epopulation (N=76) (N=143) (N=146) (N=72) (N=143) (N=150)

Endoscopic responsed at Week 48f

Total 7% 38 %e 38%e 6% 33%e 36%epopulation (N=76) (N=143) (N=146) (N=72) (N=143) (N=150)a Guselkumab 200 mg intravenous induction at Week 0, Week 4 and Week 8 followed by guselkumab 100 mgsubcutaneous q8w thereafter for up to 48 weeks.b Guselkumab 200 mg intravenous induction at Week 0, Week 4 and Week 8 followed by guselkumab 200 mgsubcutaneous q4w thereafter for up to 48 weeks.c Corticosteroid-free clinical remission is defined as CDAI score < 150 at Week 48 and not receiving corticosteroids at

Week 48.d Endoscopic response is defined as ≥ 50% improvement from baseline in SES-CD score or SES-CD Score ≤ 2.e p < 0.001f Participants who met inadequate response criteria at Week 12 were considered non-responders at Week 48, regardlessof treatment arm.

Table 17: Proportion of patients meeting major secondary efficacy endpoints with guselkumabversus ustekinumab at Week 48 in GALAXI 2 and GALAXI 3

GALAXI 2 GALAXI 3

Ustekinumab Guselkumab Guselkumab Ustekinumab Guselkumab Guselkumab6 mg/kg intravenous intravenous 6 mg/kg intravenous intravenousintravenous induction→ induction → intravenous induction→ induction →induction → 100 mg 200 mg q4w induction → 100 mg 200 mg q4w90 mg q8w q8w subcutaneous 90 mg q8w q8w subcutaneoussubcutaneous subcutaneous injectionc subcutaneous subcutaneous injectioncinjectiona injectionb injectiona injectionb

Clinical remission at Week 48 and endoscopic responsed at Week 48

Total 39% 42% 49% 28% 41%k 45%kpopulation (N=143) (N=143) (N=146) (N=148) (N=143) (N=150)

Endoscopic responsee at Week 48l

Total 42% 49% 56% 32% 47% 49%population (N=143) (N=143) (N=146) (N=148) (N=143) (N=150)

Endoscopic remissionf at Week 48

Total 20% 27% 24% 13% 24%k 19%population (N=143) (N=143) (N=146) (N=148) (N=143) (N=150)

Clinical remissiong at Week 48

Total 65% 64% 75% 61% 66% 66%population (N=143) (N=143) (N=146) (N=148) (N=143) (N=150)

Corticosteroid-free clinical remissionh at Week 48l

Total 61% 63% 71% 59% 64% 64%population (N=143) (N=143) (N=146) (N=148) (N=143) (N=150)

Durable clinical remissioni at Week 48

Total 45% 46% 52% 39% 50% 49%population (N=143) (N=143) (N=146) (N=148) (N=143) (N=150)

PRO-2 remissionj at Week 48

Total 59% 60% 69% 53% 58% 56%population (N=143) (N=143) (N=146) (N=148) (N=143) (N=150)a Ustekinumab 6 mg/kg intravenous induction at Week 0 followed by ustekinumab 90 mg subcutaneous q8w thereafter for up to48 weeks.

b Guselkumab 200 mg intravenous induction at Week 0, Week 4 and Week 8 followed by guselkumab 100 mg subcutaneous q8wthereafter for up to 48 weeks.

c Guselkumab 200 mg intravenous induction at Week 0, Week 4 and Week 8 followed by guselkumab 200 mg subcutaneous q4wthereafter for up to 48 weeks.

d A combination of clinical remission and endoscopic response as defined below.e Endoscopic response is defined as ≥ 50% improvement from baseline in SES-CD score or SES-CD Score ≤ 2.f Endoscopic remission is defined as SES-CD Score ≤ 2.g Clinical remission is defined as CDAI score < 150.h Corticosteroid-free clinical remission is defined as CDAI score < 150 at Week 48 and not receiving corticosteroids at Week 48.i Durable clinical remission is defined as CDAI < 150 for ≥ 80% of all visits between Week 12 and Week 48 (at least 8 of 10visits), which must include Week 48.j PRO-2 remission is defined as AP mean daily score at or below 1 and SF mean daily score at or below 3, and no worsening of

AP or SF from baseline.k p < 0.05l Responses at Week 48 were evaluated irrespective of clinical response at Week 12

Table 18: Proportion of patients meeting efficacy endpoints with guselkumab versusustekinumab at Week 48 in pooled GALAXI 2 and GALAXI 3

Guselkumab Guselkumab

Ustekinumab 6 mg/kg intravenous induction intravenous inductionintravenous induction → 100 mg →→ 90 mg q8w q8w 200 mg q4wsubcutaneous subcutaneous subcutaneousinjectiona injectionb injectionc

Clinical remission at Week 48 and endoscopic responsed at Week 48

Total 34% (N=291) 42% (N=286) 47% (N=296)population

Biologic naïvee 43% (N=121) 51% (N=116) 55% (N=128)

Prior biologic 26% (N=156) 37% (N=153) 41% (N=147)failuref

Endoscopic responseg at Week 48

Total 37% (N=291) 48% (N=286) 53% (N=296)population

Biologic naïvee 43% (N=121) 59% (N=116) 59% (N=128)

Prior biologic 31% (N=156) 43% (N=153) 47% (N=147)failuref

Endoscopic remissionh at Week 48

Total 16% (N=291) 25% (N=286) 21% (N=296)population

Biologic naïvee 19% (N=121) 34% (N=116) 27% (N=128)

Prior biologic 13% (N=156) 21% (N=153) 14% (N=147)failuref

Clinical remissioni at Week 48

Total 63% (N=291) 65% (N=286) 70% (N=296)population

Biologic naïvee 75% (N=121) 73% (N=116) 77% (N=128)

Prior biologic 53% (N=156) 61% (N=153) 64% (N=147)failurefa Ustekinumab 6 mg/kg intravenous induction at Week 0 followed by ustekinumab 90 mg subcutaneous q8w thereafterfor up to 48 weeks.

b Guselkumab 200 mg intravenous induction at Week 0, Week 4 and Week 8 followed by guselkumab 100 mgsubcutaneous q8w thereafter for up to 48 weeks.

c Guselkumab 200 mg intravenous induction at Week 0, Week 4 and Week 8 followed by guselkumab 200 mgsubcutaneous q4w thereafter for up to 48 weeks.

d A combination of clinical remission and endoscopic response as defined below.e An additional 14 patients in the ustekinumab group, 21 patients in the guselkumab 200 mg subcutaneous q4w group,and 17 patients in the guselkumab 100 mg subcutaneous q8w group were previously exposed to but did not fail abiological therapy.

f Includes inadequate response, loss of response, or intolerance to biologic therapy (TNF blockers, vedolizumab) for

g Endoscopic response is defined as ≥ 50% improvement from baseline in SES-CD score or SES-CD Score ≤ 2.h Endoscopic remission is defined as SES-CD Score ≤ 2.i Clinical remission is defined as CDAI score < 150.

In GALAXI 2 and GALAXI 3, the efficacy and safety of guselkumab was consistently demonstratedregardless of age, sex, race and body weight.

In the pooled GALAXI Phase III studies subpopulation analysis, patients with high inflammatoryburden after completion of induction dosing derived additional benefit from guselkumab 200 mgsubcutaneous q4w compared to the 100 mg subcutaneous q8w maintenance dose regimens. Aclinically meaningful difference was observed between the two guselkumab dose groups amongpatients with a CRP level of > 5 mg/L after completion of induction, for the endpoints of clinicalremission at Week 48 (100 mg subcutaneous q8w: 54.1% vs 200 mg subcutaneous q4w: 71.0%);endoscopic response at Week 48 (100 mg subcutaneous q8w: 36.5% vs 200 mg subcutaneousq4w: 50.5%); and PRO-2 remission at Week 48 (100 mg subcutaneous q8w: 51.8% vs 200 mgsubcutaneous q4w: 61.7%).

Clinical remission over time

CDAI scores were recorded at each patient visit. The proportion of patients in clinical remissionthrough Week 48 is presented in Figure 9.

Figure 9: Proportion of patients in clinical remission through Week 48 in pooled GALAXI 2and GALAXI 3

Greater improvements from baseline were seen at Week 12 in guselkumab treatment groups whencompared with placebo for inflammatory bowel disease (IBD)-specific quality of life assessed by

IBDQ total score. The improvements were maintained through Week 48 in both studies.

GRAVITI

In the Phase III GRAVITI study, moderately to severely active Crohn’s disease was defined as a

CDAI score of ≥ 220 and ≤ 450 and a CD (SES-CD) of ≥ 6 (or ≥ 4 for patients with isolated ilealdisease) and a mean daily SF ≥ 4 or mean daily AP score ≥ 2.

In GRAVITI, patients were randomised in a 1:1:1 ratio to receive guselkumab 400 mg subcutaneousinduction at Weeks 0, 4 and 8 followed by guselkumab 100 mg q8w subcutaneous maintenance; orguselkumab 400 mg subcutaneous induction at Weeks 0, 4 and 8, followed by guselkumab 200 mgq4w subcutaneous maintenance; or placebo. All patients in the placebo group who met rescue criteriareceived the induction dosing with guselkumab 400 mg subcutaneous at Weeks 16, 20, and 24followed by guselkumab 100 mg subcutaneous q8w.

A total of 347 patients were evaluated. The median age of patients was 36 years (ranging from 18 to83 years), 58.5% were male, and 66% identified as White, 21.9% as Asian and 2.6% as Black.

In GRAVITI, 46.4% of patients had previously failed treatment with at least one biologic therapy,46.4 % were biologic naïve, and 7.2% had previously received but had not failed a biologic. Atbaseline, 29.7% of the patients were receiving oral corticosteroids and 28.5% of the patients werereceiving conventional immunomodulators.

The results of the co-primary and major secondary efficacy endpoints compared to placebo at

Week 12 are presented in Table 19.

Table 19: Proportion of patients meeting co-primary and major secondary efficacyendpoints with guselkumab versus placebo at Week 12 in GRAVITI

Placebo Guselkumab 400 mgsubcutaneous injectiona

Co-primary efficacy endpoints

Clinical remissionb at Week 12

Total population 21% (N=117) 56%c (N=230)

Biologic naïved 25% (N=56) 50% (N=105)

Prior biologic failuree 17% (N=53) 60% (N=108)

Endoscopic responsef at Week 12

Total population 21% (N=117) 41%c (N=230)

Biologic naïved 27% (N=56) 49% (N=105)

Prior biologic failuree 17% (N=53) 33% (N=108)

Major secondary efficacy endpoints

Clinical responseg at Week 12

Total population 33% (N=117) 73%c (N=230)

Biologic naïved 38% (N=56) 68% (N=105)

Prior biologic failuree 28% (N=53) 78% (N=108)

PRO-2 remissionh at Week 12

Total population 17% (N=117) 49%c (N=230)

Biologic naïved 18% (N=56) 44% (N=105)

Prior biologic failuree 17% (N=53) 52% (N=108)a Guselkumab 400 mg subcutaneous at Week 0, Week 4 and Week 8b Clinical remission: CDAI score < 150c p< 0.001d An additional 8 patients in the placebo group and 17 patients in the guselkumab 400 mg subcutaneous group, werepreviously exposed to but did not fail a biological therapy.e Includes inadequate response, loss of response, or intolerance to biologic therapy (TNF blockers, vedolizumab) for

Crohn’s disease.f Endoscopic response: ≥ 50% improvement from baseline in SES-CD score.g Clinical response: ≥ 100-point reduction from baseline in CDAI score or CDAI score < 150.h PRO-2 remission: AP mean daily score at or below 1 and SF mean daily score at or below 3, and no worsening of APor SF from baseline.

Clinical remission at Week 24 was achieved by a significantly greater proportion of patients treatedwith guselkumab 400 mg subcutaneous induction followed by guselkumab 100 mg subcutaneous q8wor 200 mg subcutaneous q4w compared to placebo (60.9% and 58.3% vs 21.4% respectively, both p-values < 0.001). Clinical remission at Week 48 was achieved by 60% and 66.1% of patients treatedwith guselkumab 400 mg subcutaneous induction followed by guselkumab 100 mg subcutaneous q8wor 200 mg subcutaneous q4w, respectively (both p-values < 0.001 compared to placebo).

Endoscopic response at Week 48 was achieved by 44.3% and 51.3% of patients treated withguselkumab 400 mg subcutaneous induction followed by guselkumab 100 mg subcutaneous q8w or200 mg subcutaneous q4w, respectively (both p-values < 0.001 compared to placebo).

In GRAVITI, clinically meaningful improvements were observed in IBD-specific quality of life asassessed with IBDQ total score at Week 12 and Week 24 compared to placebo.

The European Medicines Agency has deferred the obligation to submit the results of studies withguselkumab in one or more subsets of the paediatric population in plaque psoriasis, psoriatic arthritis,ulcerative colitis, and Crohn’s disease (see section 4.2 for information on paediatric use).

Following a single 100 mg subcutaneous injection in healthy subjects, guselkumab reached a mean(± SD) maximum serum concentration (Cmax) of 8.09 ± 3.68 mcg/mL by approximately 5.5 days postdose. The absolute bioavailability of guselkumab following a single 100 mg subcutaneous injectionwas estimated to be approximately 49% in healthy subjects.

In patients with plaque psoriasis, following subcutaneous administrations of guselkumab 100 mg at

Weeks 0 and 4, and every 8 weeks thereafter, steady-state serum guselkumab concentrations wereachieved by Week 20. The mean (± SD) steady-state trough serum guselkumab concentrations in two

Phase III studies in patients with plaque psoriasis were 1.15 ± 0.73 mcg/mL and 1.23 ± 0.84 mcg/mL.

The pharmacokinetics of guselkumab in patients with psoriatic arthritis was similar to that in patientswith psoriasis. Following subcutaneous administration of guselkumab 100 mg at Weeks 0, 4, andevery 8 weeks thereafter, mean steady-state trough serum guselkumab concentration was alsoapproximately 1.2 mcg/mL. Following subcutaneous administration of guselkumab 100 mg every4 weeks, mean steady-state trough serum guselkumab concentration was approximately 3.8 mcg/mL.

The pharmacokinetics of guselkumab were similar in patients with ulcerative colitis and Crohn’sdisease. Following the recommended intravenous induction dose regimen of guselkumab 200 mg at

Weeks 0, 4, and 8, mean peak serum guselkumab concentration at Week 8 was 68.27 mcg/mL inpatients with ulcerative colitis, and 70.5 mcg/mL in patients with Crohn’s disease.

Following the recommended subcutaneous induction dose regimen of guselkumab 400 mg at

Weeks 0, 4, and 8, mean peak serum concentration was estimated to be 27.7 mcg/mL in patients with

Crohn’s disease. The total systemic exposure (AUC) after the recommended induction dose regimenwas similar following subcutaneous and intravenous induction.

Following subcutaneous maintenance dosing of guselkumab 100 mg every 8 weeks or guselkumab200 mg every 4 weeks in patients with ulcerative colitis, mean steady-state trough serum guselkumabconcentrations were approximately 1.4 mcg/mL and 10.7 mcg/mL, respectively.

Following subcutaneous maintenance dosing of guselkumab 100 mg every 8 weeks or guselkumab200 mg every 4 weeks in patients with Crohn’s disease, mean steady-state trough serum guselkumabconcentrations were approximately 1.2 mcg/mL and 10.1 mcg/mL, respectively.

Mean volume of distribution during the terminal phase (Vz) following a single intravenousadministration to healthy subjects ranged from approximately 7 to 10 L across studies.

The exact pathway through which guselkumab is metabolised has not been characterised. As a human

IgG mAb, guselkumab is expected to be degraded into small peptides and amino acids via catabolicpathways in the same manner as endogenous IgG.

Mean systemic clearance (CL) following a single intravenous administration to healthy subjectsranged from 0.288 to 0.479 L/day across studies. Mean half-life (T1/2) of guselkumab wasapproximately 17 days in healthy subjects and approximately 15 to 18 days in patients with plaquepsoriasis across studies, and approximately 17 days in patients with ulcerative colitis or Crohn’sdisease.

Population pharmacokinetic analyses indicated that concomitant use of NSAIDs, AZA, 6-MP, oralcorticosteroids and csDMARDs such as MTX, did not affect the clearance of guselkumab.

The systemic exposure of guselkumab (Cmax and AUC) increased in an approximatelydose-proportional manner following a single subcutaneous injection at doses ranging from 10 mg to300 mg in healthy subjects or patients with plaque psoriasis. Serum guselkumab concentrations wereapproximately dose proportional following intravenous administration in patients with ulcerativecolitis or Crohn’s disease.

The pharmacokinetics of guselkumab in paediatric patients have not been established.

No specific studies have been conducted in elderly patients. Of the 1 384 plaque psoriasis patientsexposed to guselkumab in Phase III clinical studies and included in the population pharmacokineticanalysis, 70 patients were 65 years of age or older, including 4 patients who were 75 years of age orolder. Of the 746 psoriatic arthritis patients exposed to guselkumab in Phase III clinical studies, a totalof 38 patients were 65 years of age or older, and no patients were 75 years of age or older. Of the859 ulcerative colitis patients exposed to guselkumab in Phase II/III clinical studies and included inthe population pharmacokinetic analysis, a total of 52 patients were 65 years of age or older, and9 patients were 75 years of age or older. Of the 1 009 Crohn’s disease patients exposed to guselkumabin Phase III clinical studies and included in the population pharmacokinetic analysis, a total of39 patients were 65 years of age or older, and 5 patients were 75 years of age or older.

Population pharmacokinetic analyses in plaque psoriasis, psoriatic arthritis, ulcerative colitis, and

Crohn’s disease patients indicated no apparent changes in CL/F estimate in patients ≥ 65 years of agecompared to patients < 65 years of age, suggesting no dose adjustment is needed for elderly patients.

No specific study has been conducted to determine the effect of renal or hepatic impairment on thepharmacokinetics of guselkumab. Renal elimination of intact guselkumab, an IgG mAb, is expected tobe low and of minor importance; similarly, hepatic impairment is not expected to influence clearanceof guselkumab as IgG mAbs are mainly eliminated via intracellular catabolism. Based on populationpharmacokinetic analyses, creatinine clearance or hepatic function did not have a meaningful impacton guselkumab clearance.

Clearance and volume of distribution of guselkumab increases as body weight increases, however,observed clinical trial data indicate that dose adjustment for body weight is not warranted.

Non-clinical data reveal no special hazard for humans based on conventional studies of safetypharmacology, repeat-dose toxicity, toxicity to reproduction and pre- and post-natal development.

In repeat-dose toxicity studies in cynomolgus monkeys, guselkumab was well tolerated viaintravenous and subcutaneous routes of administration. A weekly subcutaneous dose of 50 mg/kg tomonkeys resulted in exposure (AUC) values that were at least 23 times the maximum clinicalexposures following a dose of 200 mg given intravenously. Additionally, there were no adverseimmunotoxicity or cardiovascular safety pharmacology effects noted during the conduct of therepeat-dose toxicity studies or in a targeted cardiovascular safety pharmacology study in cynomolgusmonkeys.

There were no preneoplastic changes observed in histopathology evaluations of animals treated up to24 weeks, or following the 12-week recovery period during which active substance was detectable inthe serum.

No mutagenicity or carcinogenicity studies were conducted with guselkumab.

Guselkumab could not be detected in breast milk from cynomolgus monkeys as measured at post-natalday 28.

Histidine

Histidine monohydrochloride monohydrate

Polysorbate 80 (E433)

Sucrose

Water for injections

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinalproducts.

2 years.

Store in a refrigerator (2°C - 8°C). Do not freeze.

Keep the pre-filled syringe or pre-filled pen in the outer carton in order to protect from light.

Tremfya 100 mg solution for injection in pre-filled syringe1 mL solution in a pre-filled glass syringe with a bromobutyl rubber stopper, a fixed needle and aneedle shield, assembled in an automatic needle guard.

Tremfya is available in packs containing one pre-filled syringe and in multipacks containing 2 (2packs of 1) pre-filled syringes.

Not all pack sizes may be marketed.

Tremfya 100 mg solution for injection in pre-filled pen1 mL solution in a pre-filled glass syringe with a bromobutyl rubber stopper, assembled in a pre-filledpen with an automatic needle guard.

Tremfya is available in a pack containing one pre-filled pen and in a multipack containing 2 (2 packsof 1) pre-filled pens.

Not all pack sizes may be marketed.

After removing the pre-filled syringe or pre-filled pen from the refrigerator, keep the pre-filled syringeor pre-filled pen inside the carton and allow to reach room temperature by waiting for 30 minutesbefore injecting Tremfya. The pre-filled syringe or pre-filled pen should not be shaken.

Prior to use, a visual inspection of the pre-filled syringe or pre-filled pen is recommended. Thesolution should be clear, colourless to light yellow, and may contain a few small white or clearparticles. Tremfya should not be used if the solution is cloudy or discoloured, or contains largeparticles.

Each pack is provided with an ‘Instructions for use’ leaflet that fully describes the preparation andadministration of the pre-filled syringe or pre-filled pen.

Any unused medicinal product or waste material should be disposed of in accordance with localrequirements.

Janssen-Cilag International NV

Turnhoutseweg 30

B-2340 Beerse

Belgium

Tremfya 100 mg solution for injection in pre-filled syringe

EU/1/17/1234/001 1 pre-filled syringe

EU/1/17/1234/004 2 pre-filled syringes

Tremfya 100 mg solution for injection in pre-filled pen

EU/1/17/1234/002 1 pre-filled pen

EU/1/17/1234/003 2 pre-filled pens

Date of first authorisation: 10 November 2017

Date of latest renewal:15 July 2022

Detailed information on this medicinal product is available on the website of the European Medicines

Agency https://www.ema.europa.eu