SKYRIZI 360mg 150mg / ml injection solution in the cartridge medication leaflet

Skyrizi 360 mg solution for injection in cartridge

Skyrizi 180 mg solution for injection in cartridge

Skyrizi 90 mg solution for injection in pre-filled syringe

Skyrizi 360 mg solution for injection in cartridge

Each cartridge contains 360 mg of risankizumab in 2.4 mL solution.

Skyrizi 180 mg solution for injection in cartridge

Each cartridge contains 180 mg of risankizumab in 1.2 mL solution.

Skyrizi 90 mg solution for injection in pre-filled syringe

Each pre-filled syringe contains 90 mg of risankizumab in 1 mL solution.

Risankizumab is a humanised immunoglobulin G1 (IgG1) monoclonal antibody produced in Chinese

Hamster Ovary cells using recombinant DNA technology.

Excipients with known effect (90 mg solution for injection only)

This medicinal product contains 164 mg sorbitol per 360 mg dose.

For the full list of excipients, see section 6.1.

Solution for injection (injection)

Skyrizi 180 mg and 360 mg solution for injection in cartridge

The solution is colourless to yellow and clear to slightly opalescent.

Skyrizi 90 mg solution for injection in pre-filled syringe

The solution is colourless to slightly yellow and clear to slightly opalescent.

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

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

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

The recommended dose is 600 mg administered by intravenous infusion at week 0, week 4, andweek 8, followed by 360 mg administered by subcutaneous injection at week 12, and every 8 weeksthereafter. Consideration should be given to discontinuing treatment in patients who have shown noevidence of therapeutic benefit by week 24.

For the posology of the initial intravenous dosing regimen, see section 4.2 of the Skyrizi 600 mgconcentrate for solution for infusion Summary of Product Characteristics.

The recommended induction dose is 1 200 mg administered by intravenous infusion at week 0,week 4, and week 8. Starting at week 12 and every 8 weeks thereafter, the recommended maintenancedose is based on individual patient presentation:

* A dose of 180 mg administered by subcutaneous injection is recommended for patients withadequate improvement in disease activity after induction

* A dose of 360 mg administered by subcutaneous injection is recommended for patients withinadequate improvement in disease activity after induction

Consideration should be given to discontinuing treatment in patients who have shown no evidence oftherapeutic benefit by week 24.

For the posology of the initial intravenous dosing regimen, see section 4.2 of the Skyrizi 600 mgconcentrate for solution for infusion Summary of Product Characteristics.

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 subjects aged ≥65 years.

No specific studies were conducted to assess the effect of hepatic or renal impairment on thepharmacokinetics of Skyrizi. These conditions are generally not expected to have any significantimpact on the pharmacokinetics of monoclonal antibodies and no dose adjustments are considerednecessary (see section 5.2).

The safety and efficacy of Skyrizi in children aged 0-17 years for the treatment of Crohn’s disease andulcerative colitis have not yet been established. Currently available data are described in section 5.1and 5.2 but no recommendation on posology can be made.

Overweight patients

No dose adjustment is required (see section 5.2).

Skyrizi is administered by subcutaneous injection.

The injection should be administered in the thigh or abdomen. Skyrizi should not be injected into areaswhere the skin is tender, bruised, erythematous, indurated or damaged.

Skyrizi 180 mg and 360 mg solution for injection in cartridge

Patients may self-inject Skyrizi after training in subcutaneous injection technique with the on-bodyinjector. Patients should be instructed to read the ‘Instructions for use’ provided in the package leafletbefore administration.

Skyrizi 90 mg solution for injection in pre-filled syringe

This medicinal product should be administered by a healthcare professional.

Four pre-filled syringes should be injected to administer the full 360 mg dose. The four injectionsshould be administered at different anatomic locations (see administration instructions provided withthe package leaflet).

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.

Risankizumab may increase the risk of infection.

In patients with a chronic infection, a history of recurrent infection, or known risk factors for infection,risankizumab should be used with caution. Treatment with risankizumab should not be initiated inpatients with any clinically important active infection until the infection resolves or is adequatelytreated.

Patients treated with risankizumab should be instructed to seek medical advice if signs or symptoms ofclinically important chronic or acute infection occur. If a patient develops such an infection or is notresponding to standard therapy for the infection, the patient should be closely monitored andrisankizumab should not be administered until the infection resolves.

Prior to initiating treatment with risankizumab, patients should be evaluated for tuberculosis (TB)infection. Patients receiving risankizumab should be monitored for signs and symptoms of active TB.

Anti-TB therapy should be considered prior to initiating risankizumab in patients with a past history oflatent or active TB in whom an adequate course of treatment cannot be confirmed.

Prior to initiating therapy with risankizumab, completion of all appropriate immunisations should beconsidered according to current immunisation guidelines. If a patient has received live vaccination(viral or bacterial), it is recommended to wait at least 4 weeks prior to starting treatment withrisankizumab. Patients treated with risankizumab should not receive live vaccines during treatmentand for at least 21 weeks after treatment (see section 5.2).

Serious hypersensitivity reactions, including anaphylaxis, have been reported with use ofrisankizumab (see section 4.8). If a serious hypersensitivity reaction occurs, administration ofrisankizumab should be discontinued immediately and appropriate therapy initiated.

Skyrizi 180 mg and 360 mg solution for injection in cartridge

This medicinal product contains less than 1 mmol sodium (23 mg) per cartridge, that is to sayessentially ‘sodium-free’.

Skyrizi 90 mg solution for injection in pre-filled syringe

Sorbitol

This medicinal product contains 164 mg sorbitol per 360 mg dose.

The additive effect of concomitantly administered products containing sorbitol (or fructose) anddietary intake of sorbitol (or fructose) should be taken into account.

This medicinal product contains less than 1 mmol sodium (23 mg) per 360 mg dose, that is to sayessentially ‘sodium free’.

Risankizumab is not expected to undergo metabolism by hepatic enzymes or renal elimination.

Interactions between risankizumab and inhibitors, inducers, or substrates of medicinal productmetabolising enzymes are not expected and no dose adjustment is needed (see section 5.2).

Concomitant immunosuppressive therapy

The safety and efficacy of risankizumab in combination with immunosuppressants, includingbiologics, have not been evaluated.

Women of childbearing potential should use an effective method of contraception during treatmentand for at least 21 weeks after treatment.

There are no or limited amount of data (less than 300 pregnancy outcomes) from the use ofrisankizumab in pregnant women. Animal studies do not indicate direct or indirect harmful effectswith respect to reproductive toxicity. As a precautionary measure, it is preferable to avoid the use ofrisankizumab during pregnancy.

It is unknown whether risankizumab is excreted in human milk. Human IgGs are known to be excretedin breast milk during the first few days after birth, which decreases to low concentrations soonafterwards; consequently, a risk to the breast-fed infant cannot be excluded during this short period. Adecision should be made whether to discontinue/abstain from risankizumab therapy, taking intoaccount the benefit of breast-feeding to the child and the benefit of risankizumab therapy to thewoman.

The effect of risankizumab on human fertility has not been evaluated. Animal studies do not indicatedirect or indirect harmful effects with respect to fertility.

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

The most frequently reported adverse reactions were upper respiratory infections (15.6% in Crohn’sdisease and 26.2% in ulcerative colitis).

Adverse reactions for risankizumab from clinical studies (Table 1) are listed by MedDRA systemorgan class and are based on 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) andnot known (cannot be estimated from the available data). Within each frequency grouping, adversereactions are presented in order of decreasing seriousness.

Table 1: List of adverse reactions

System Organ Class Frequency Adverse reactions

Infections and Very common Upper respiratoryinfestations infectionsa

Common Tinea infectionsb

Uncommon Folliculitis

Immune system Rare Anaphylactic reactionsdisorders

Nervous system Common Headachecdisorders

Skin and subcutaneous Common Pruritustissue disorders Rash

Eczema

Uncommon Urticaria

General disorders and Common Fatiguedadministration site Injection site reactionseconditionsa Includes: respiratory tract infection (viral, bacterial or unspecified), sinusitis(including acute), rhinitis, nasopharyngitis, pharyngitis (including viral), tonsillitis,laryngitis, tracheitisb Includes: tinea pedis, tinea cruris, body tinea, tinea versicolor, tinea manuum,onychomycosis, tinea infectionc Includes: headache, tension headache, sinus headached Includes: fatigue, asthenia, malaisee Includes: injection site bruising, erythema, haematoma, haemorrhage, irritation,pain, pruritus, reaction, swelling, induration, hypersensitivity, nodule, rash, urticaria,vesicles, warmth; infusion site erythema, extravasation, reaction, swelling

Over the entire psoriasis programme including long-term exposure to risankizumab, the rate ofinfections was 75.5 events per 100 subject-years. The majority of cases were non-serious and mild tomoderate in severity and did not lead to discontinuation of risankizumab. The rate of serious infectionswas 1.7 events per 100 subject-years (see section 4.4).

Overall, the safety profile observed in patients with Crohn’s disease treated with risankizumab wasconsistent with the safety profile observed in patients across indications.

The rate of infections in the pooled data from the 12-week induction studies was 83.3 events per 100subject-years in subjects treated with risankizumab 600 mg intravenously compared to 117.7 eventsper 100 subject-years in placebo. The rate of serious infections was 3.4 events per 100 subject-years insubjects treated with risankizumab 600 mg intravenously compared to 16.7 events per 100 subject-years in placebo (see section 4.4).

The rate of infections in the 52-week maintenance study was 57.7 events per 100 subject-years insubjects treated with risankizumab 360 mg subcutaneously after risankizumab induction compared to76.0 events per 100 subject-years in subjects who received placebo after risankizumab induction. Therate of serious infections was 6.0 events per 100 subject-years in subjects treated with risankizumab360 mg subcutaneously after risankizumab induction compared to 5.0 events per 100 subject-years insubjects who received placebo after risankizumab induction (see section 4.4).

Overall, the safety profile observed in patients with ulcerative colitis treated with risankizumab wasconsistent with the safety profile observed in patients across indications.

The rate of infections in the pooled data from the 12-week induction study was 78.3 events per100 subject-years in subjects treated with risankizumab 1 200 mg intravenously compared to 74.2events per 100 subject-years in placebo. The rate of serious infections was 3.0 events per 100 subject-years in subjects treated with risankizumab 1 200 mg intravenously compared to 5.4 events per100 subject-years in placebo (see section 4.4).

The rate of infections in the 52-week maintenance study was 67.4 events per 100 subject-years insubjects treated with risankizumab 180 mg subcutaneously and 56.5 events per 100 subject-years insubjects treated with risankizumab 360 mg subcutaneously after risankizumab induction compared to64.6 events per 100 subject-years in subjects who received placebo after risankizumab induction. Therate of serious infections was 1.1 events per 100 subject-years in subjects treated with risankizumab180 mg subcutaneously and 0.6 events per 100 subject-years in subjects treated with risankizumab360 mg subcutaneously after risankizumab induction compared to 2.3 events per 100 subject-years insubjects who received placebo after risankizumab induction (see section 4.4).

For subjects with Crohn’s disease treated with risankizumab at the recommended intravenousinduction and subcutaneous maintenance doses for up to 64 weeks in CD clinical trials, treatment-emergent anti-drug antibodies and neutralizing antibodies were detected in 3.4% (2/58) and 0% (0/58)of evaluated subjects, respectively.

For subjects with ulcerative colitis treated with risankizumab at the recommended intravenousinduction and subcutaneous maintenance doses (180 mg or 360 mg) for up to 64 weeks in ulcerativecolitis clinical trials, treatment-emergent anti-drug antibodies and neutralising antibodies weredetected in 8.9% (8/90) and 6.7% (6/90) for the 180 mg subcutaneous dose, or 4.4% (4/91) and 2.2%(2/91) for the 360 mg subcutaneous dose, of evaluated subjects, respectively.

Antibodies to risankizumab including neutralizing antibodies were not associated with changes inclinical response or safety.

There is limited safety information in subjects aged ≥65 years.

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.

In the event of overdose, it is recommended that the patient be monitored for any signs or symptomsof adverse reactions and appropriate symptomatic treatment be instituted immediately.

Pharmacotherapeutic group: Immunosuppressants, interleukin inhibitors, ATC code: L04AC18

Risankizumab is a humanised immunoglobulin G1 (IgG1) monoclonal antibody that selectively bindswith high affinity to the p19 subunit of human interleukin 23 (IL-23) cytokine without binding to IL-12 and inhibits its interaction with the IL-23 receptor complex. IL-23 is a cytokine that is involved ininflammatory and immune responses. By blocking IL-23 from binding to its receptor, risankizumabinhibits IL-23-dependent cell signalling and release of proinflammatory cytokines.

In a study of subjects with psoriasis, expression of genes associated with the IL-23/IL-17 axis wasdecreased in the skin after single doses of risankizumab. Reductions in epidermal thickness,infiltration of inflammatory cells, and expression of psoriatic disease markers were also observed inpsoriatic lesions.

In a Phase 2 study of subjects with Crohn’s disease, expression of genes associated with the IL-23/Th17 axis were decreased in gut tissue after multiple doses of risankizumab. Reductions in faecalcalprotectin (FCP), serum C reactive protein (CRP) and IL-22 were also observed after multiple dosesin Phase 3 induction studies in Crohn’s patients. Decreases in FCP, CRP and serum IL-22 weremaintained out to week 52 of the maintenance study.

In a Phase 2b/3 study of subjects with ulcerative colitis, statistically significant and clinicallymeaningful reduction from baseline was observed in the inflammatory biomarkers, FCP and CRP, andin the IL-23 pathway-associated biomarker, serum IL-22, at week 12 of the induction study. Decreasesin FCP, CRP and serum IL-22 were maintained out to week 52 of the maintenance study.

The efficacy and safety of risankizumab were assessed in 1 419 subjects with moderately to severelyactive Crohn’s disease in three multicentre, randomised, double-blind, placebo-controlled clinicalstudies. Enrolled subjects were 16 years of age or older with a Crohn’s Disease Activity Index (CDAI)of 220 to 450, an average daily stool frequency (SF) ≥4 and/or average daily abdominal pain score(APS) ≥2, and a Simple Endoscopic Score for CD (SES-CD) of ≥6, or ≥4 for isolated ileal disease,excluding the narrowing component and confirmed by a central reviewer.

There were two 12-week intravenous induction studies (ADVANCE and MOTIVATE), whichincluded a 12-week extension period for subjects who did not achieve SF/APS clinical response (≥30% decrease in SF and/or ≥ 30% decrease in APS and both not worse than baseline) at week 12.

ADVANCE and MOTIVATE were followed by a 52-week randomised withdrawal study ofsubcutaneous maintenance treatment (FORTIFY) that enrolled subjects with SF/APS clinical responseto intravenous induction treatment, representing at least 64 weeks of therapy.

ADVANCE and MOTIVATE

In studies ADVANCE and MOTIVATE, subjects were randomised to receive risankizumab at either600 mg (recommended dose), 1 200 mg, or placebo, at week 0, week 4, and week 8.

In ADVANCE, 58% (491/850) subjects had failed or were intolerant to treatment with one or morebiologic therapies (prior biologic failure), and 42% (359/850) had failed or were intolerant to therapywith conventional therapies but not biologic therapies (without prior biologic failure). In ADVANCE,among the subjects without prior biologic failure, (87%) 314/359 were naïve to biologic therapy andthe remaining 13% had received a biologic but never failed or demonstrated intolerance. All patientsin MOTIVATE had prior biologic failure.

In both studies, a greater proportion of subjects treated with risankizumab achieved the co-primaryendpoints of clinical remission at week 12 and endoscopic response at week 12 compared to placebo.

Enhanced SF/APS clinical response and clinical remission were significant as early as week 4 insubjects treated with risankizumab and continued to improve through week 12 (Table 2).

Table 2. Efficacy results in ADVANCE and MOTIVATE

ADVANCE MOTIVATE

Placebo Risankizumab Treatment Placebo Risankizumab Treatmentintravenously 600 mg differenced intravenous 600 mg differenced(N=175) intravenously (95% CI) ly intravenously (95% CI)% (N=336) (N=187) (N=191)% % %

Co-primary endpoints

Clinicalremission at 22% 43% 22% 15%19% 35%e [14%, 30%]a [6%, 24%]bweek 12

Endoscopic28% 18%response at 12% 40% 11% 29%f [21%, 35%]a [10%, 25%]aweek 12

Additional endpoints

Enhanced

SF/APS15% 14%clinical 31% 46%b 32% 45%[6%, 23%] [4%, 23%]cresponse atweek 4g

Enhanced

SF/APS21% 23%clinical 42% 63% 39% 62%[12%, 30%]a [13%, 33%]aresponse atweek 12g

CDAI <150 at 8% 10%10% 18% 11% 21%week 4 [1%, 14%]c [2%, 17%]c

CDAI <150 at 21% 22%25% 45% a 20% 42%week 12 [12%, 29%] [13%, 31%]a

Mucosal(N=173) (N=336) 14% (N=186) (N=190) 9%healing ath 8% 21% [8%, 19%]a 4% 14% [4%, 15%]bweek 12

Endoscopic15% 15%remission at 9% 24%a 4% 19%[9%, 21%] [9%, 21%]aweek 12ia Statistically significant under multiplicity-control for risankizumab vs placebo comparison (p<0.001).b Statistically significant under multiplicity-control for risankizumab vs placebo comparison (p≤0.01).c Nominal p ≤ 0.05 risankizumab vs placebo comparison.d Adjusted treatment difference.

e Clinical remission based on SF/APS: average daily SF ≤2.8 and not worse than baseline and average daily

AP score ≤1 and not worse than baseline.f Endoscopic response: greater than 50% decrease in SES-CD from baseline, or a decrease of at least 2 pointsfor subjects with a baseline score of 4 and isolated ileal disease.g Enhanced SF/APS clinical response: ≥60% decrease in average daily SF and/or ≥35% decrease in averagedaily AP score and both not worse than Baseline, and/or clinical remission.h Mucosal healing: SES-CD ulcerated surface subscore of 0 in subjects with a subscore of ≥1 at Baseline.i Endoscopic remission: SES-CD ≤4 and at least a 2 point reduction versus Baseline and no subscore greaterthan 1 in any individual variable.

At week 12, a higher proportion of subjects treated with risankizumab achieved a decrease of at least100 points in baseline CDAI compared to placebo (ADVANCE, risankizumab =60%, placebo=37%,p<0.001; MOTIVATE, risankizumab =60%, placebo=30%, p<0.001).

At week 12, a higher proportion of subjects treated with risankizumab achieved both enhanced

SF/APS clinical response and endoscopic response at week 12 compared to placebo (ADVANCE,risankizumab =31%, placebo=8%, p<0.001; MOTIVATE, risankizumab =21%, placebo=7%,p<0.001).

The results for the co-primary endpoints for the subgroups (without allowing for multiplicity) ofsubjects with and without prior biologic failure are presented in Table 3.

Table 3. Efficacy results at week 12 in subgroups of subjects with prior biologic treatmentfailure and subjects without prior biologic failure in ADVANCE

ADVANCE

Risankizumab 600 mg Treatment difference

Placebo intravenously(95% CI)

Clinical remission per SF/AP Score

Prior biologic failure 23% (N=97) 41% (N=195) 18% [7%, 29%]

Without prior biologic 27% [15%, 39%]21% (N=78) 48% (N=141)failure

Endoscopic response

Prior biologic failure 11% (N=97) 33% (N=195) 21% [12%, 31%]

Without prior biologic 38% [27%, 49%]13% (N=78) 50% (N=141)failure

In ADVANCE, a higher proportion of subjects treated with risankizumab with and without priorbiologic failure achieved CDAI<150 compared to placebo (With prior biologic failure, risankizumab=42%, placebo=26%; Without prior biologic failure, risankizumab =49%, placebo=23%).

CD-related hospitalisations

Rates of CD-related hospitalisations through week 12 were lower in subjects treated withrisankizumab compared to placebo (ADVANCE, risankizumab =3%, placebo=12%, p<0.001;

MOTIVATE, risankizumab =3%, placebo=11%, p≤0.01).

FORTIFY

The maintenance study FORTIFY evaluated 462 subjects with SF/APS clinical response to 12 weeksof risankizumab intravenous induction treatment in studies ADVANCE and MOTIVATE. Subjectswere randomised to continue to receive a maintenance regimen of risankizumab 360 mgsubcutaneously (recommended dose), or risankizumab 180 mg subcutaneously every 8 weeks, or towithdraw from risankizumab induction and receive placebo subcutaneously every 8 weeks for up to 52weeks.

The co-primary endpoints were clinical remission at week 52 and, endoscopic response at week 52.

Co-primary endpoints were also measured in subjects with and without prior biologic failure (see

Table 4).

Table 4. Efficacy results in FORTIFY at week 52 (64 weeks from initiation of induction dose)

FORTIFY

Risankizumab Risankizumab Treatment differenceintravenous induction/ intravenous induction/ (95% CI)

Placebo subcutaneouslyf Risankizumab(N=164) % 360 mgsubcutaneously(N=141) %

Co-primary endpoints

Clinical remission 40% 52% 15% [5%, 25%]a,g

Prior biologic failure 34% (N=123) 48% (N=102) 14% [1%,27%]

Without prior biologic failure 56% (N=41) 62% (N=39) 5% [-16%,27%]

Endoscopic response 22% 47% 28% [19%, 37%]b,g

Prior biologic failure 20% (N=123) 44% (N=102) 23% [11%, 35%]

Without prior biologic failure 27% (N=41) 54% (N=39) 27% [6%, 48%]

Additional endpoints

Enhanced SF/APS clinical49% 59% 13% [2%, 23%]e,gresponse

Maintenance of clinical (N = 91) (N = 72)h 21% [6%, 35%]d,gremission 51% 69%

Endoscopic remission 13% 39% 28% [20%, 37%]c,g(N = 162) (N = 141)

Mucosal healing 22% [14%, 30%]c,g10% 31%a Statistically significant under multiplicity-control for risankizumab vs placebo comparison (p≤0.01).b Statistically significant under multiplicity-control for risankizumab vs placebo comparison (p<0.001).c Nominal p<0.001 risankizumab vs placebo comparison without overall type I error control.d Nominal p≤0.01 risankizumab vs placebo comparison without overall type I error control.

e Nominal p≤0.05 risankizumab vs placebo comparison without overall type I error control.f The induction-only group consisted of subjects who achieved clinical response to risankizumab inductiontherapy and were randomised to receive placebo in the maintenance study (FORTIFY).g Adjusted treatment difference.h Maintenance of clinical remission: clinical remission at week 52 in subjects with clinical remission at week0.

Deep remission (clinical remission and endoscopic remission) at week 52 was observed at higher ratesin subjects treated with risankizumab intravenously/risankizumab subcutaneously compared tosubjects who received risankizumab intravenously /placebo subcutaneously (28% vs. 10%,respectively, nominal p<0.001).

At week 52, a higher proportion of subjects treated with risankizumab intravenously/risankizumabsubcutaneously achieved CDAI < 150 compared to risankizumab intravenously /placebosubcutaneously (52% vs. 41%, respectively, nominal p≤0.01). A higher proportion of subjects treatedwith risankizumab intravenously/ risankizumab subcutaneously achieved a decrease of at least100 points in baseline CDAI score compared to subjects treated with risankizumab intravenously/placebo subcutaneously (62% vs. 48%, respectively, nominal p≤ 0.01).

91 subjects who did not demonstrate SF/APS clinical response 12 weeks after risankizumab inductionin studies ADVANCE and MOTIVATE received subcutaneous 360 mg dose of risankizumab atweek 12 and week 20. Of these subjects, 64% (58/91) achieved SF/APS clinical response at week 24;33 of the subjects achieving SF/APS clinical response enrolled in FORTIFY and continued receivingrisankizumab 360 mg subcutaneously every 8 weeks for up to 52 weeks. Among these subjects, 55%(18/33) achieved clinical remission and 45% (15/33) achieved endoscopic response at week 52.

During FORTIFY, 30 subjects had loss of response to risankizumab 360 mg subcutaneously treatmentand received rescue treatment with risankizumab (1 200 mg intravenous single dose, followed by360 mg subcutaneously every 8 weeks). Of these subjects, 57% (17/30) achieved SF/APS clinicalresponse at week 52. In addition, 20% (6/30) and 34% (10/29) of subjects achieved clinical remissionand endoscopic response at week 52, respectively.

Health-related and quality of life outcomes

Health-related quality of life was assessed by the Inflammatory Bowel Disease Questionnaire (IBDQ)and 36-Item Short Form Health Survey (SF-36). Improvement in fatigue was evaluated by the

Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) scale. Work productivitywas assessed by the Work Productivity and Activity Impairment CD (WPAI-CD) Questionnaire.

At week 12 of ADVANCE and MOTIVATE, subjects treated with risankizumab achieved clinicallymeaningful improvements from baseline in IBDQ total score, all IBDQ domain scores (bowelsymptoms, systemic function, emotional function, and social function), SF-36 Physical and Mental

Component Summary Score, FACIT-Fatigue and WPAI-CD compared to placebo. For WPAI-CDgreater reductions in impairment while working, overall work impairment, and activity impairmentwere demonstrated in ADVANCE; and greater reduction in activity impairment was demonstrated in

MOTIVATE. These improvements were maintained in subjects treated with risankizumabintravenously/risankizumab subcutaneously in FORTIFY through week 52.

The efficacy and safety of risankizumab was assessed in subjects with moderately to severely activeulcerative colitis in two multicentre, randomised, double-blind, placebo-controlled clinical studies.

Enrolled subjects were ≥ 18 and ≤ 80 years of age with adapted Mayo Score (aMS) of 5 to 9 (using the

Mayo scoring system, excluding Physician’s Global Assessment) with an endoscopic subscore (ES) of2 or 3 on screening endoscopy, confirmed by central review.

The 12-week intravenous induction study (INSPIRE) included a 12-week extension period for subjectswho did not achieve clinical response [defined as a decrease from baseline in the aMS ≥ 2 points and≥ 30% from baseline, and a decrease in rectal bleeding subscore (RBS) ≥ 1 or an absolute RBS ≤ 1] at

Week 12. INSPIRE was followed by a 52-week randomised withdrawal study of subcutaneousmaintenance treatment (COMMAND) that enrolled subjects with clinical response to 12 weeks ofrisankizumab intravenous induction treatment, representing at least 64 weeks of therapy.

INSPIRE

In study INSPIRE, 975 subjects were randomised and received either risankizumab 1 200 mg orplacebo, at week 0, week 4, and week 8.

In INSPIRE, 52% (503/975) of subjects had failed (inadequate response or intolerance) one or morebiologics therapies, JAK inhibitors, and/or S1P receptor modulators. Of these 503 subjects, 488 (97%)failed biologics and 90 (18%) failed JAK inhibitors.

Enrolled subjects were permitted to use a stable dose of oral corticosteroids (up to 20 mg/dayprednisone or equivalent), immunomodulators, and aminosalicylates. At baseline in INSPIRE, 36% ofsubjects received corticosteroids, 17% of subjects received immunomodulators and 73% of subjectsreceived aminosalicylates. Patient disease activity was moderate (aMS ≤7) in 58% of subjects andsevere (aMS >7) in 42% of subjects.

In INSPIRE, a significantly greater proportion of subjects treated with risankizumab achieved theprimary endpoint of clinical remission per aMS [defined as stool frequency subscore (SFS) ≤ 1, andnot greater than baseline, RBS = 0, and ES ≤ 1 without evidence of friability] at week 12 compared toplacebo (Table 5). Results of the primary endpoint and key secondary endpoints are listed in Table 5.

Table 5. Efficacy results in INSPIRE at week 12

Placebo Risankizumab Treatmentintravenously 1 200 mg difference

Endpoint (N=325) intravenously (95% CI)% (N=650)%

Disease activity and UC symptoms14%f

Clinical remissionab 6% 20%[10%, 18%]7%

With biologic and/or JAK inhibitor failure 4% (N=170) 11% (N=333)[3%, 12%]21%

Without biologic and/or JAK inhibitor failure 8% (N=155) 30% (N=317)[15%, 28%]29%f

Clinical responsec 36% 64%[22%, 35%]24%

With biologic and/or JAK inhibitor failure 31% (N=170) 55% (N=333)[15%, 33%]33%

Without biologic and/or JAK inhibitor failure 41% (N=155) 74% (N=317)[24%, 42%]

Endoscopic and histologic assessment24%f

Mucosal healingd 12% 37%[19%, 29%]16%

With biologic and/or JAK inhibitor failure 10% (N=170) 26% (N=333)[9%, 22%]33%

Without biologic and/or JAK inhibitor failure 14% (N=155) 48% (N=317)[26%, 41%]17%f

Histologic-endoscopic mucosal healinge 8% 24%[12%, 21%]9%

With biologic and/or JAK inhibitor failure 7% (N=170) 16% (N=333)[3%, 14%]25%

Without biologic and/or JAK inhibitor failure 8% (N=155) 33% (N=317)[18%, 32%]a Primary endpointb Clinical remission per aMS: SFS ≤ 1, and not greater than baseline, RBS = 0, and ES ≤ 1 without evidenceof friabilityc Clinical response per aMS: decrease from Baseline ≥ 2 points and ≥ 30%, and a decrease in RBS ≥ 1 or anabsolute RBS ≤ 1d ES ≤ 1 without the evidence of friabilitye ES ≤ 1 without the evidence of friability and Geboes score ≤ 3.1 (indicating neutrophil infiltration in <5% ofcrypts, no crypt destruction and no erosions, ulcerations or granulation tissue)f p < 0.00001, adjusted treatment difference (95% CI)

Clinical disease activity and symptoms

The partial adapted Mayo score (paMS) is composed of SFS and RBS. Clinical response per paMS isdefined as a decrease of ≥1 point and ≥30% from Baseline and a decrease in RBS ≥1 or an absolute

RBS ≤1. The results of clinical response per paMS over time in INSPIRE are shown in Figure 1. Onsetof efficacy was rapid with a greater proportion of subjects treated with risankizumab achieving clinicalresponse as early as week 4 compared to placebo (52% vs 31%, respectively, p < 0.00001).

Figure 1. Proportion of subjects achieving clinical response per paMS over time in inductionstudy INSPIRE0 4 8 12

Weeks

Placebo intravenously (N=325)

Risankizumab 1 200 mg intravenously (N=650)

A significantly greater proportion of subjects treated with risankizumab compared to placebo had noabdominal pain (36% vs 26%, respectively, p < 0.01) and no bowel urgency (44% vs 28%,respectively, p < 0.00001) at week 12.

Other UC symptoms

Number of faecal incontinence episodes per week was reduced in a significantly greater amount insubjects treated with risankizumab compared to placebo at week 12 (change from baseline inrisankizumab = -3.8, placebo = -2.2, p = 0.00003).

The proportion of subjects who had no nocturnal bowel movements was significantly greater insubjects treated with risankizumab compared to placebo at week 12 (67% vs 43%, respectively,p < 0.00001).

The proportion of subjects who had no tenesmus was significantly greater in subjects treated withrisankizumab compared to placebo at week 12 (49% vs 30%, respectively, p < 0.00001).

Number of days with sleep interruption due to UC symptoms per week were reduced in a significantlygreater amount in subjects treated with risankizumab compared to placebo at week 12 (change frombaseline in risankizumab = -2.5, placebo = -1.5, p < 0.00001).

UC-related hospitalisations

Rates of UC-related hospitalisations through week 12 were significantly lower in subjects treated withrisankizumab compared to placebo (1% vs 6%, respectively, p < 0.00001).

Response Rate (%) and 95% CI

Extended treatment in week 12 non-responders

A total of 141 subjects who did not demonstrate clinical response at week 12 of risankizumabinduction in INSPIRE received either subcutaneous 180 mg or 360 mg dose of risankizumab at week12 and week 20. Of the 71 subjects who received risankizumab 180 mg subcutaneously and 70subjects who received risankizumab 360 mg subcutaneously, 56% and 57% achieved clinical responseat week 24, respectively.

COMMAND

The maintenance study COMMAND evaluated 548 subjects with clinical response after 12 weeks ofrisankizumab intravenous induction treatment in study INSPIRE. Subjects were randomised to receivea maintenance regimen of risankizumab 180 mg subcutaneously or 360 mg subcutaneously every 8weeks, or to withdraw from risankizumab induction and receive placebo subcutaneously every 8weeks for up to 52 weeks.

In COMMAND, 75% (411/548) of subjects had failed (inadequate response or intolerance) one ormore biologics therapies, JAK inhibitors, and/or S1P receptor modulators prior to induction baseline.

Of these 411 subjects, 407 (99%) failed biologics and 78 (19%) failed JAK inhibitors.

In COMMAND, a significantly greater proportion of the above 548 subjects treated with risankizumab180 mg subcutaneously or risankizumab 360 mg subcutaneously achieved the primary endpoint ofclinical remission per aMS at week 52 compared to placebo (see Table 6). Results of the primaryendpoint and key secondary endpoints are listed in Table 6.

Table 6. Efficacy results in COMMAND at week 52 (64 weeks from initiation of induction dose)

Risankizumab Risankizumab Risankizumab Treatment differenceintravenous intravenous intravenous (97.5% CI)++induction/ induction/ induction/

Risankizumab Risankizumab

Placebo Risankizumab Risankizumabintravenous intravenous

Endpoint subcutaneousl 180 mg 360 mg+ induction/ induction/y subcutaneously subcutaneousl

Risankizumab Risankizumab(N=183) % (N=179) % y180 mg 360 mg(N=186) %subcutaneousl subcutaneouslyy

Disease activity and UC symptoms16%h 14%h

Clinical remissionab 25% 40% 38%[6%, 27%] [4%, 24%]

With biologic and/or 13% 6%23% (N=138) 37% (N=134) 29% (N=139)

JAK inhibitor failure [1%, 26%] [-6%, 18%]

Without biologic and/or 20% 31%31% (N=45) 51% (N=45) 62% (N=47)

JAK inhibitor failure [-3%, 43%] [8%, 53%]

Maintenance of clinical 29%h 13%kc 40% (N=53) 70% (N=44) 50% (N=40)remission [7%, 51%] [-11%, 36%]

With biologic and/or 28% 7%37% (N=35) 65% (N=26) 44% (N=25)

JAK inhibitor failure [0%, 56%] [-22%, 36%]

Without biologic and/or 33% 16%44% (N=18) 77% (N=18) 60% (N=15)

JAK inhibitor failure [-2%, 67%] [-23%, 54%]

Corticosteroid-free 16% h 14% hd 25% 40% 37%clinical remission [6%, 26%] [3%, 24%]

With biologic and/or 13% 6%23% (N=138) 36% (N=134) 29% (N=139)

JAK inhibitor failure [0%, 25%] [-6%, 18%]

Without biologic and/or 20% 28%31% (N=45) 51% (N=45) 60% (N=47)

JAK inhibitor failure [-3%, 43%] [6%, 51%]17%i 11%j

Clinical responsee 52% 68% 62%[6%, 28%] [0%, 23%]

With biologic and/or 18% 11%46% (N=138) 63% (N=134) 57% (N=139)

JAK inhibitor failure [4%, 31%] [-2%, 25%]

Without biologic and/or 11% 8%71% (N=45) 82% (N=45) 79% (N=47)

JAK inhibitor failure [-9%, 31%] [-13%, 28%]

Endoscopic and histologic assessment20% h 17% h

Mucosal healingf 32% 51% 48%[9%, 31%] [7%, 28%]

With biologic and/or 17% 8%30% (N=138) 48% (N=134) 39% (N=139)

JAK inhibitor failure [4%, 30%] [-4%, 21%]

Without biologic and/or 24% 41%36% (N=45) 60% (N=45) 76% (N=47)

JAK inhibitor failure [1%, 47%] [19%, 62%]

Histologic-endoscopic 20%h 20% h23% 43% 42%mucosal healingg [10%, 31%] [10%, 30%]

With biologic and/or 17% 11%22% (N=138) 39% (N=134) 33% (N=139)

JAK inhibitor failure [5%, 29%] [-1%, 23%]

Without biologic and/or 26% 40%29% (N=45) 55% (N=45) 69% (N=47)

JAK inhibitor failure [3%, 49%] [19%, 62%]+ The induction-only group consisted of subjects who achieved clinical response to risankizumabinduction therapy and were randomised to receive placebo in the maintenance study (COMMAND).++ Adjusted difference for the overall treatment difference.a Primary endpointb Clinical remission per aMS: SFS ≤ 1, and not greater than baseline, RBS = 0, and ES ≤ 1 withoutevidence of friabilityc Clinical remission per aMS at Week 52 among subjects who achieved clinical remission at the end ofinduction treatmentd Clinical remission per aMS at Week 52 and corticosteroid-free for ≥90 dayse Clinical response per aMS: decrease from Baseline ≥ 2 points and ≥ 30%, and a decrease in RBS ≥ 1or an absolute RBS ≤ 1f ES of ≤ 1 without the evidence of friabilityg ES ≤ 1 without the evidence of friability and Geboes score ≤ 3.1 (indicating neutrophil infiltration in<5% of crypts, no crypt destruction and no erosions, ulcerations or granulation tissue)h Statistically significant under multiplicity-control for risankizumab vs placebo comparison (p ≤ 0.01).i Nominal p ≤ 0.01 risankizumab vs placebo comparisonj Nominal p ≤ 0.05 risankizumab vs placebo comparisonk p = 0.2234

Clinical disease activity and symptoms

A significantly greater proportion of subjects treated with risankizumab intravenously/risankizumab180 mg subcutaneously compared to risankizumab intravenously/placebo had no abdominal pain (47%vs 30%, respectively, p < 0.001) and no bowel urgency (54% vs 31%, respectively, p < 0.00001) atweek 52. A greater proportion of subjects treated with risankizumab intravenously/risankizumab360 mg subcutaneously compared to risankizumab intravenously/placebo had no bowel urgency (49%vs 31%, respectively, p < 0.001) at week 52, and a numerically higher proportion of subjects had noabdominal pain compared to risankizumab intravenously/placebo (38% vs 30%, respectively,p = 0.0895) at week 52.

Other UC symptoms

The proportion of subjects who had no nocturnal bowel movements was greater in subjects treatedwith risankizumab intravenously/risankizumab 180 mg subcutaneously and risankizumabintravenously/risankizumab 360 mg subcutaneously compared to risankizumab intravenously/placeboat week 52 (42% and 43% vs 30%, p < 0.01 and p < 0.001, respectively).

The proportion of subjects who had no tenesmus was greater in subjects treated with risankizumabintravenously/risankizumab 180 mg subcutaneously and risankizumab intravenously/risankizumab360 mg subcutaneously compared to risankizumab intravenously/placebo at week 52 (37% and 37%vs 23%, respectively, p < 0.01).

UC-related hospitalisations

Occurrence of UC-related hospitalisations through week 52 were numerically lower in subjects treatedwith risankizumab intravenously/risankizumab 180 mg subcutaneously and risankizumabintravenously/risankizumab 360 mg subcutaneously compared to risankizumab intravenously/placebo(0.6 per 100 subject-years and 1.2 per 100 subject-years vs 3.1 per 100 subject-years, p = 0.0949 andp = 0.2531, respectively).

Endoscopic and histologic assessment

Endoscopic remission (normalisation of the endoscopic appearance of the mucosa) was defined as ESof 0. At week 12 of INSPIRE, a significantly greater proportion of subjects treated with risankizumabcompared to placebo achieved endoscopic remission (11% vs 3%, respectively, p < 0.00001). At week52 of COMMAND, a significantly greater proportion of subjects treated with risankizumabintravenously/risankizumab 180 mg subcutaneously and risankizumab intravenously/risankizumab360 mg subcutaneously compared to risankizumab intravenously/placebo achieved endoscopicremission (23% and 24% vs 15%, respectively, p < 0.05).

Deep mucosal healing was defined as ES of 0 and Geboes score < 2.0 (indicating no neutrophil incrypts or lamina propria and no increase in eosinophil, no crypt destruction, and no erosions,ulcerations or granulation tissue). At week 12 of INSPIRE, a significantly greater proportion ofsubjects treated with risankizumab compared to placebo achieved deep mucosal healing (6% vs 1%,respectively, p < 0.00001). At week 52 of COMMAND, a numerically higher proportion of subjectstreated with risankizumab intravenously/risankizumab 180 mg subcutaneously and risankizumabintravenously/risankizumab 360 mg subcutaneously compared to risankizumab intravenously/placeboachieved deep mucosal healing (13% and 16% vs 10%, p = 0.2062 and p = 0.0618, respectively).

In COMMAND, maintenance of mucosal healing at week 52 (ES ≤1 without friability) was seen in agreater proportion of subjects treated with risankizumab intravenously/risankizumab 180 mgsubcutaneously and risankizumab intravenously/risankizumab 360 mg subcutaneously compared torisankizumab intravenously/placebo among subjects who achieved mucosal healing at the end ofinduction (74% and 54% vs 47%, p < 0.01 and p = 0.5629, respectively).

Rescue treatment

During COMMAND, subjects who had loss of response to risankizumab subcutaneous treatmentreceived rescue treatment with risankizumab (a single intravenous induction dose, followed by 360 mgsubcutaneously every 8 weeks). Among these subjects, in the risankizumab 180 mg subcutaneouslyand risankizumab 360 mg subcutaneously treatment group, 85% (17/20) and 74% (26/35) achievedclinical response at week 52, respectively. In addition, 24% (6/25) and 35% (13/37) of subjectsachieved clinical remission per aMS, and 38% (10/26) and 45% (17/38) of subjects achievedendoscopic improvement at week 52 in the risankizumab 180 mg subcutaneously and risankizumab360 mg subcutaneously treatment group, respectively.

Week 24 responders

A total of 100 subjects did not demonstrate clinical response after 12 weeks of induction treatment,received either subcutaneous 180 mg (N=56) or 360 mg (N=44) dose of risankizumab at week 12 andweek 20, demonstrated clinical response at week 24, and continued receiving risankizumab 180 mg or360 mg subcutaneously every 8 weeks for up to 52 weeks in COMMAND. Among these subjects,46% and 45% achieved clinical response per aMS at week 52, and 18% and 23% achieved clinicalremission per aMS at week 52, for risankizumab 180 mg and 360 mg subcutaneously respectively.

Health-related and quality of life outcomes

Subjects treated with risankizumab achieved clinically meaningful improvements from baseline in the

Inflammatory Bowel Disease Questionnaire (IBDQ) (bowel symptoms, systemic function, emotionalfunction, and social function) compared to placebo. Changes from baseline in IBDQ total score atweek 12 with risankizumab compared to placebo were 42.6 and 24.3, respectively. Changes frombaseline in IBDQ total score at week 52 were 52.6, 50.3 and 35.0 in subjects treated withrisankizumab intravenous/risankizumab 180 mg subcutaneously, risankizumabintravenous/risankizumab 360 mg subcutaneously and risankizumab intravenous/placebo,respectively.

Subjects receiving risankizumab experienced significantly greater improvement from baseline infatigue, as measured by FACIT-F score at week 12 compared to placebo. Changes from baseline in

FACIT-F score at week 12 with risankizumab compared to placebo were 7.9 and 3.3, respectively.

Changes from baseline in FACIT-F score at week 52 were 10.9, 10.3 and 7.0 in subjects treated withrisankizumab intravenously/risankizumab 180 mg subcutaneously, risankizumabintravenously/risankizumab 360 mg subcutaneously and risankizumab intravenously/placebo,respectively.

The European Medicines Agency has deferred the obligation to submit the results of studies with

Skyrizi in one or more subsets of the paediatric population in the treatment of Crohn’s disease andulcerative colitis (see section 4.2 for information on paediatric use).

The pharmacokinetics of risankizumab was similar between plaque psoriasis and psoriatic arthritis,and between Crohn’s disease and ulcerative colitis.

Risankizumab exhibited linear pharmacokinetics with dose-proportional increase in exposure acrossdose ranges of 18 to 360 mg and 0.25 to 1 mg/kg administered subcutaneously, and 200 to 1 800 mgand 0.01 to 5 mg/kg administered intravenously.

Following subcutaneous dosing of risankizumab, peak plasma concentrations were achieved between3-14 days after dosing with an estimated absolute bioavailability of 74-89%. With dosing of 150 mg atweek 0, week 4 and every 12 weeks thereafter, estimated steady-state peak and trough plasmaconcentrations are 12 and 2 µg/mL, respectively.

In subjects with Crohn’s disease treated with 600 mg intravenous induction dose at weeks 0, 4, and 8followed by 360 mg subcutaneous maintenance dose at week 12 and every 8 weeks thereafter,maximum median peak and trough concentrations are estimated to be 156 and 38.8 µg/mLrespectively during the induction period (weeks 8-12) and steady-state median peak and troughconcentrations are estimated to be 28.0 and 8.13 µg/mL respectively during the maintenance period(weeks 40-48).

In subjects with ulcerative colitis treated with 1 200 mg intravenous induction dose at weeks 0, 4, and8 followed by 180 mg or 360 mg subcutaneous maintenance dose at week 12 and every 8 weeksthereafter, maximum median peak and trough concentrations are estimated to be 350 and 87.7 µg/mLrespectively during the induction period (weeks 8-12) and steady-state median peak and troughconcentrations are estimated to be 19.6 and 4.64 µg/mL for the 180 mg subcutaneous dose and 39.2and 9.29 µg/mL for the 360 mg subcutaneous dose, respectively, during the maintenance period(weeks 40-48).

The mean (±standard deviation) steady-state volume of distribution (Vss) of risankizumab was11.4 (±2.7) L in Phase 3 studies in subjects with psoriasis, indicating that the distribution ofrisankizumab is primarily confined to the vascular and interstitial spaces. In a typical 70 kg subjectwith Crohn’s disease, Vss was 7.68 L.

Therapeutic IgG monoclonal antibodies are typically degraded into small peptides and amino acids viacatabolic pathways in the same manner as endogenous IgGs. Risankizumab is not expected to bemetabolised by cytochrome P450 enzymes.

The mean (±standard deviation) systemic clearance (CL) of risankizumab was 0.3 (±0.1) L/day in

Phase 3 studies in subjects with psoriasis. The mean terminal elimination half-life of risankizumabranged from 28 to 29 days in Phase 3 studies in subjects with psoriasis. For a typical 70 kg subjectwith Crohn’s disease, CL was 0.30 L/day and terminal elimination half-life was 21 days.

As an IgG1 monoclonal antibody, risankizumab is not expected to be filtered by glomerular filtrationin the kidneys or to be excreted as an intact molecule in the urine.

Risankizumab exhibited linear pharmacokinetics with approximately dose-proportional increases insystemic exposure (Cmax and AUC) in the evaluated dose ranges of 18 to 360 mg or 0.25 to 1 mg/kgsubcutaneous administration and 200 to 1800 mg and 0.01 to 5 mg/kg administered intravenously inhealthy subjects or subjects with psoriasis, Crohn’s disease or ulcerative colitis.

Interaction studies were conducted in subjects with plaque psoriasis, Crohn’s disease, or ulcerativecolitis to assess the effect of repeated administration of risankizumab on the pharmacokinetics ofcytochrome P450 (CYP) sensitive probe substrates. The exposure of caffeine (CYP1A2 substrate),warfarin (CYP2C9 substrate), omeprazole (CYP2C19 substrate), metoprolol (CYP2D6 substrate) andmidazolam (CYP3A substrate) following risankizumab treatment were comparable to their exposuresprior to risankizumab treatment, indicating no clinically meaningful interactions through theseenzymes.

Population pharmacokinetic analyses indicated that risankizumab exposure was not impacted byconcomitant medicinal products used by some subjects with plaque psoriasis during the clinicalstudies. Similar lack of impact by concomitant medicinal products was observed based on populationpharmacokinetic analyses in Crohn’s disease or ulcerative colitis.

The pharmacokinetics of risankizumab in paediatric subjects under 16 years of age has not beenestablished. Of the 1 574 subjects with Crohn’s disease exposed to risankizumab, 12 were 16 to17 years old. Risankizumab exposures in 16 to 17 year-old subjects with Crohn’s disease were similarto those in adults. Age was not found to have any significant impact on risankizumab exposures basedon the population pharmacokinetic analyses.

Of the 2 234 subjects with plaque psoriasis exposed to risankizumab, 243 were 65 years or older and24 subjects were 75 years or older. Of the 1 574 subjects with Crohn’s disease exposed torisankizumab, 72 were 65 years or older and 5 subjects were 75 years or older. Of the 1 512 subjectswith ulcerative colitis exposed to risankizumab, 103 were 65 years or older and 8 subjects were75 years or older. No overall differences in risankizumab exposure were observed between older andyounger subjects who received risankizumab.

No specific studies have been conducted to determine the effect of renal or hepatic impairment on thepharmacokinetics of risankizumab. Based on population pharmacokinetic analyses, serum creatininelevels, creatinine clearance, or hepatic function markers (ALT/AST/bilirubin) did not have ameaningful impact on risankizumab clearance in subjects with psoriasis, Crohn’s disease, or ulcerativecolitis.

As an IgG1 monoclonal antibody, risankizumab is mainly eliminated via intracellular catabolism andis not expected to undergo metabolism via hepatic cytochrome P450 enzymes or renal elimination.

Risankizumab clearance and volume of distribution increase as body weight increases which mayresult in reduced efficacy in subjects with high body weight (>130 kg). However, this observation isbased on a limited number of subjects with plaque psoriasis. Body weight had no clinically meaningfulimpact on risankizumab exposure or efficacy in psoriatic arthritis, Crohn’s disease, or ulcerativecolitis. No dose adjustment based on body weight is currently recommended.

Gender or race

The clearance of risankizumab was not significantly influenced by gender or race in adult subjectswith plaque psoriasis, Crohn’s disease or ulcerative colitis. No clinically meaningful differences inrisankizumab exposure were observed in Chinese or Japanese subjects compared to Caucasian subjectsin clinical pharmacokinetic studies in healthy volunteers.

Nonclinical data revealed no special hazard for humans based on repeat-dose toxicity studies includingsafety pharmacology evaluations and an enhanced pre- and post- natal developmental toxicity study incynomolgus monkeys at doses of up to 50 mg/kg/week, producing exposures 10 times the clinicalexposures during induction at a dose of 600 mg intravenous every 4 weeks and 39 times the clinicalexposures for maintenance when given 360 mg subcutaneously every 8 weeks for Crohn’s disease. Forulcerative colitis, exposures were 5 times the clinical exposures during induction at a dose of 1 200 mgintravenously every 4 weeks and 65 or 32 times the clinical exposures for maintenance when given180 or 360 mg subcutaneously every 8 weeks.

Mutagenicity and carcinogenicity studies have not been conducted with risankizumab. In a 26-weekchronic toxicology study in cynomolgus monkeys at doses of up to 50 mg/kg/week (7 times theclinical exposures during induction at a dose of 600 mg intravenous every 4 weeks and 28 times theclinical exposures for maintenance when given 360 mg subcutaneously every 8 weeks for Crohn’sdisease and 3 times the clinical exposures during induction at a dose of 1 200 mg intravenously every4 weeks and 45 or 23 times the clinical exposures for maintenance when given 180 or 360 mgsubcutaneously every 8 weeks for ulcerative colitis), there were no pre-neoplastic or neoplastic lesionsobserved and no adverse immunotoxicity or cardiovascular effects were noted.

Skyrizi 180 mg and 360 mg solution for injection in cartridge

Sodium acetate trihydrate

Acetic acid

Trehalose dihydrate

Polysorbate 20

Water for injections

Skyrizi 90 mg solution for injection in pre-filled syringe

Disodium succinate hexahydrate

Polysorbate 20

Sorbitol

Succinic acid

Water for injections

This medicinal product must not be mixed with other medicinal products.

2 years

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

The cartridge may be stored out of the refrigerator (up to a maximum of 25°C) for up to 24 hours.

Keep the cartridge or pre-filled syringes in the outer carton in order to protect from light.

Skyrizi 360 mg solution for injection in cartridge

A 360 mg solution in a single use cartridge made with cyclic olefin resin with coated chlorobutylrubber septum and coated chlorobutyl rubber piston as product-contact materials, and a resin cap. Thecartridge assembly is co-packed with an on-body injector (administration device). The fluid pathwithin the on-body injector contains polyvinyl chloride tubing and a stainless steel 29-gauge needle.

The on-body injector contains silver oxide-zinc batteries and an adhesive skin patch made frompolyester with an acrylic adhesive. The administration device is designed for use with the provided360 mg cartridge.

Skyrizi 360 mg is available in packs containing 1 cartridge and 1 on-body injector.

Skyrizi 180 mg solution for injection in cartridge

A 180 mg solution in a single use cartridge made with cyclic olefin resin with coated chlorobutylrubber septum and coated chlorobutyl rubber piston as product-contact materials, and a resin cap. Thecartridge assembly is co-packed with an on-body injector (administration device). The fluid pathwithin the on-body injector contains polyvinyl chloride tubing and a stainless steel 29-gauge needle.

The on-body injector contains silver oxide-zinc batteries and an adhesive skin patch made frompolyester with an acrylic adhesive. The administration device is designed for use with the provided180 mg cartridge.

Skyrizi 180 mg is available in packs containing 1 cartridge and 1 on-body injector.

Skyrizi 90 mg solution for injection in pre-filled syringe

Pre-filled glass syringe with a fixed needle and needle cover, assembled in an automatic needle guard.

Skyrizi 90 mg is available in packs containing 4 pre-filled syringes.

Not all presentations may be marketed.

Skyrizi 180 mg and 360 mg solution for injection in cartridge

Before injecting, the carton should be removed from the refrigerator and allowed to reach roomtemperature, out of direct sunlight, for 45 to 90 minutes without removing the cartridge from thecarton.

Prior to use, a visual inspection of the cartridge is recommended. The solution is free from foreignparticles and practically free from product-related particles. Skyrizi should not be used if the solutionis cloudy or discoloured, or contains large particles. Do not shake the cartridge.

The solution should be colourless to yellow and clear to slightly opalescent.

Skyrizi 90 mg solution for injection in pre-filled syringe

Before injecting, the carton should be removed from the refrigerator and allow to reach roomtemperature out of direct sunlight, for 15 to 30 minutes without removing the pre-filled syringes fromthe carton.

Prior to use, a visual inspection of each pre-filled syringe is recommended. The solution may contain afew translucent to white product-related particles. Skyrizi should not be used if the solution is cloudyor discoloured, or contains large particles. Do not shake the pre-filled syringe.

The solution should be colourless to slightly yellow and clear to slightly opalescent.

Comprehensive instructions for use are provided in the package leaflet.

Each on-body injector with cartridge and pre-filled syringe are for single use only.

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

AbbVie Deutschland GmbH & Co. KG

Knollstrasse67061 Ludwigshafen

Germany

Skyrizi 360 mg solution for injection in cartridge

EU/1/19/1361/005

Skyrizi 180 mg solution for injection in cartridge

EU/1/19/1361/007

Skyrizi 90 mg solution for injection in pre-filled syringe

EU/1/19/1361/006

Date of first authorisation: 26 April 2019

Date of latest renewal: 5 January 2024

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

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