COSENTYX 75mg 75mg / 0.5ml solution for injection in pre-filled syringe medication leaflet

Cosentyx 75 mg solution for injection in pre-filled syringe

Each pre-filled syringe contains 75 mg secukinumab in 0.5 ml.

Secukinumab is a recombinant fully human monoclonal antibody produced in Chinese Hamster Ovary(CHO) cells.

For the full list of excipients, see section 6.1.

Solution for injection (injection)

The solution is clear and colourless to slightly yellow.

Cosentyx is indicated for the treatment of moderate to severe plaque psoriasis in children andadolescents from the age of 6 years who are candidates for systemic therapy.

Enthesitis-related arthritis (ERA)

Cosentyx, alone or in combination with methotrexate (MTX), is indicated for the treatment of activeenthesitis-related arthritis in patients 6 years and older whose disease has responded inadequately to,or who cannot tolerate, conventional therapy (see section 5.1).

Juvenile psoriatic arthritis (JPsA)

Cosentyx, alone or in combination with methotrexate (MTX), is indicated for the treatment of activejuvenile psoriatic arthritis in patients 6 years and older whose disease has responded inadequately to,or who cannot tolerate, conventional therapy (see section 5.1).

Cosentyx is intended for use under the guidance and supervision of a physician experienced in thediagnosis and treatment of conditions for which Cosentyx is indicated.

Paediatric plaque psoriasis (adolescents and children from the age of 6 years)

The recommended dose is based on body weight (Table 1) and administered by subcutaneous injectionwith initial dosing at weeks 0, 1, 2, 3 and 4, followed by monthly maintenance dosing. Each 75 mgdose is given as one subcutaneous injection of 75 mg. Each 150 mg dose is given as one subcutaneousinjection of 150 mg. Each 300 mg dose is given as one subcutaneous injection of 300 mg or as twosubcutaneous injections of 150 mg.

Table 1 Recommended dose for paediatric plaque psoriasis

Body weight at time of dosing Recommended dose<25 kg 75 mg25 to <50 kg 75 mg≥50 kg 150 mg (*may be increased to 300 mg)

*Some patients may derive additional benefit from the higher dose.

Enthesitis-related arthritis (ERA) and juvenile psoriatic arthritis (JPsA)

The recommended dose is based on body weight (Table 2) and administered by subcutaneous injectionat weeks 0, 1, 2, 3, and 4, followed by monthly maintenance dosing. Each 75 mg dose is given as onesubcutaneous injection of 75 mg. Each 150 mg dose is given as one subcutaneous injection of 150 mg.

Table 2 Recommended dose for juvenile idiopathic arthritis

Body weight at time of dosing Recommended dose<50 kg 75 mg≥50 kg 150 mg

Cosentyx may be available in other strengths and/or presentations depending on the individualtreatment needs.

For all of the above indications, available data suggest that a clinical response is usually achievedwithin 16 weeks of treatment. Consideration should be given to discontinuing treatment in patientswho have shown no response by 16 weeks of treatment. Some patients with an initial partial responsemay subsequently improve with continued treatment beyond 16 weeks.

The safety and efficacy of Cosentyx in children with plaque psoriasis and in the juvenile idiopathicarthritis (JIA) categories of ERA and JPsA below the age of 6 years have not been established.

The safety and efficacy of Cosentyx in children below the age of 18 years in other indications have notyet been established. No data are available.

Renal impairment/hepatic impairment

Cosentyx has not been studied in these patient populations. No dose recommendations can be made.

Cosentyx is to be administered by subcutaneous injection. If possible, areas of the skin that showpsoriasis should be avoided as injection sites. The syringe must not be shaken.

After proper training in subcutaneous injection technique, patients may self-inject Cosentyx or beinjected by a caregiver if a physician determines that this is appropriate. However, the physicianshould ensure appropriate follow-up of patients. Patients or caregivers should be instructed to injectthe full amount of Cosentyx according to the instructions provided in the package leaflet.

Comprehensive instructions for administration are given in the package leaflet.

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

Clinically important, active infection, 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.

Secukinumab has the potential to increase the risk of infections. Serious infections have been observedin patients receiving secukinumab in the post-marketing setting. Caution should be exercised whenconsidering the use of secukinumab in patients with a chronic infection or a history of recurrentinfection.

Patients should be instructed to seek medical advice if signs or symptoms suggestive of an infectionoccur. If a patient develops a serious infection, the patient should be closely monitored andsecukinumab should not be administered until the infection resolves.

In clinical studies, infections have been observed in patients receiving secukinumab (see section 4.8).

Most of these were mild or moderate upper respiratory tract infections such as nasopharyngitis and didnot require treatment discontinuation.

Related to the mechanism of action of secukinumab, non-serious mucocutaneous candida infectionswere more frequently reported for secukinumab than placebo in the psoriasis clinical studies (3.55 per100 patient years for secukinumab 300 mg versus 1.00 per 100 patient years for placebo) (seesection 4.8).

Tuberculosis (active and/or latent reactivation) has been reported in patients treated with secukinumab.

Patients should be evaluated for tuberculosis infection prior to initiating treatment with secukinumab.

Secukinumab should not be given to patients with active tuberculosis (see section 4.3). In patients withlatent tuberculosis, anti-tuberculosis therapy should be considered prior to initiation of secukinumab asper clinical guidelines. Patients receiving secukinumab should be monitored for signs and symptomsof active tuberculosis.

Inflammatory bowel disease (including Crohn’s disease and ulcerative colitis)

Cases of new or exacerbations of inflammatory bowel disease have been reported with secukinumab(see section 4.8). Secukinumab is not recommended in patients with inflammatory bowel disease. If apatient develops signs and symptoms of inflammatory bowel disease or experiences an exacerbation ofpre-existing inflammatory bowel disease, secukinumab should be discontinued and appropriatemedical management should be initiated.

Rare cases of anaphylactic reactions and angioedema have been observed in patients receivingsecukinumab. If an anaphylactic reaction, angioedema or other serious allergic reactions occur,administration of secukinumab should be discontinued immediately and appropriate therapy initiated.

Latex-sensitive individuals

The removable needle cap of Cosentyx 75 mg solution for injection in pre-filled syringe contains aderivative of natural rubber latex. No natural rubber latex has to date been detected in the removableneedle cap. Nevertheless, the use of Cosentyx 75 mg solution for injection in pre-filled syringe inlatex-sensitive individuals has not been studied and there is therefore a potential risk ofhypersensitivity reactions which cannot be completely ruled out.

Live vaccines should not be given concurrently with secukinumab.

Patients receiving secukinumab may receive concurrent inactivated or non-live vaccinations. In astudy, after meningococcal and inactivated influenza vaccinations, a similar proportion of healthyvolunteers treated with 150 mg of secukinumab and those treated with placebo were able to mount anadequate immune response of at least a 4-fold increase in antibody titres to meningococcal andinfluenza vaccines. The data suggest that secukinumab does not suppress the humoral immuneresponse to the meningococcal or influenza vaccines.

Prior to initiating therapy with Cosentyx, it is recommended that paediatric patients receive allage-appropriate immunisations as per current immunisation guidelines.

Concomitant immunosuppressive therapy

In psoriasis studies, the safety and efficacy of secukinumab in combination with immunosuppressants,including biologics, or phototherapy have not been evaluated. Secukinumab was administeredconcomitantly with methotrexate (MTX), sulfasalazine and/or corticosteroids in arthritis studies(including in patients with psoriatic arthritis and ankylosing spondylitis). Caution should be exercisedwhen considering concomitant use of other immunosuppressants and secukinumab (see alsosection 4.5).

Hepatitis B virus reactivation can occur in patients treated with secukinumab. In accordance withclinical guidelines for immunosuppressants, testing patients for HBV infection is to be consideredbefore initiating treatment with secukinumab. Patients with evidence of positive HBV serology shouldbe monitored for clinical and laboratory signs of HBV reactivation during secukinumab treatment. Ifreactivation of HBV occurs while on secukinumab, discontinuation of the treatment should beconsidered, and patients should be treated according to clinical guidelines.

Live vaccines should not be given concurrently with secukinumab (see also section 4.4).

In a study in adult subjects with plaque psoriasis, no interaction was observed between secukinumaband midazolam (CYP3A4 substrate).

No interaction was seen when secukinumab was administered concomitantly with methotrexate(MTX) and/or corticosteroids in arthritis studies (including in patients with psoriatic arthritis and axialspondyloarthritis).

Women of childbearing potential should use an effective method of contraception during treatmentand for at least 20 weeks after treatment.

There are no adequate data from the use of secukinumab in pregnant women.

Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity(see section 5.3). As a precautionary measure, it is preferable to avoid the use of Cosentyx duringpregnancy.

It is not known whether secukinumab is excreted in human milk. Immunoglobulins are excreted inhuman milk and it is not known if secukinumab is absorbed systemically after ingestion. Because ofthe potential for adverse reactions in nursing infants from secukinumab, a decision on whether todiscontinue breast-feeding during treatment and up to 20 weeks after treatment or to discontinuetherapy with Cosentyx must be made taking into account the benefit of breast-feeding to the child andthe benefit of therapy to the woman.

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

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

The most frequently reported adverse reactions are upper respiratory tract infections (17.1%) (mostfrequently nasopharyngitis, rhinitis).

Adverse reactions from clinical studies and post-marketing reports (Table 3) are listed by MedDRAsystem organ class. Within each system organ class, the adverse reactions are ranked by frequency,with the most frequent reactions first. Within each frequency grouping, adverse reactions are presentedin order of decreasing seriousness. In addition, the corresponding frequency category for each adversereaction is 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); and not known(cannot be estimated from the available data).

Over 20 000 patients have been treated with secukinumab in blinded and open-label clinical studies invarious indications (plaque psoriasis, psoriatic arthritis, axial spondyloarthritis, hidradenitissuppurativa [HS] and other autoimmune conditions), representing 34 908 patient years of exposure. Ofthese, over 14 000 patients were exposed to secukinumab for at least one year. The safety profile ofsecukinumab is consistent across all indications.

Table 3 List of adverse reactions in clinical studies1) and post-marketing experience

System organ class Frequency Adverse reaction

Infections and Very common Upper respiratory tract infectionsinfestations Common Oral herpes

Uncommon Oral candidiasis

Otitis externa

Lower respiratory tract infections

Tinea pedis

Not known Mucosal and cutaneous candidiasis (includingoesophageal candidiasis)

Blood and lymphatic Uncommon Neutropeniasystem disorders

Immune system Rare Anaphylactic reactionsdisorders Angioedema

Nervous system Common Headachedisorders

Eye disorders Uncommon Conjunctivitis

Respiratory, thoracic Common Rhinorrhoeaand mediastinaldisorders

Gastrointestinal Common Diarrhoeadisorders Nausea

Uncommon Inflammatory bowel disease

Skin and subcutaneous Common Eczematissue disorders Uncommon Urticaria

Dyshidrotic eczema

Rare Exfoliative dermatitis2)

Hypersensitivity vasculitis

Not known Pyoderma gangrenosum

General disorders and Common Fatigueadministration siteconditions1) Placebo-controlled clinical studies (phase III) in plaque psoriasis, PsA, AS, nr-axSpA and HSpatients exposed to 300 mg, 150 mg, 75 mg or placebo up to 12 weeks (psoriasis) or 16 weeks(PsA, AS, nr-axSpA and HS) treatment duration2) Cases were reported in patients with psoriasis diagnosis

In the placebo-controlled period of clinical studies in plaque psoriasis (a total of 1 382 patients treatedwith secukinumab and 694 patients treated with placebo for up to 12 weeks), infections were reportedin 28.7% of patients treated with secukinumab compared with 18.9% of patients treated with placebo.

The majority of infections consisted of non-serious and mild to moderate upper respiratory tractinfections, such as nasopharyngitis, which did not necessitate treatment discontinuation. There was anincrease in mucosal or cutaneous candidiasis, consistent with the mechanism of action, but the caseswere mild or moderate in severity, non-serious, responsive to standard treatment and did notnecessitate treatment discontinuation. Serious infections occurred in 0.14% of patients treated withsecukinumab and in 0.3% of patients treated with placebo (see section 4.4).

Over the entire treatment period (a total of 3 430 patients treated with secukinumab for up to 52 weeksfor the majority of patients), infections were reported in 47.5% of patients treated with secukinumab(0.9 per patient-year of follow-up). Serious infections were reported in 1.2% of patients treated withsecukinumab (0.015 per patient-year of follow-up).

Infection rates observed in psoriatic arthritis and axial spondyloarthritis (ankylosing spondylitis andnon-radiographic axial spondyloarthritis) clinical studies were similar to those observed in thepsoriasis studies.

Patients with hidradenitis suppurativa are more susceptible to infections. In the placebo-controlledperiod of clinical studies in hidradenitis suppurativa (a total of 721 patients treated with secukinumaband 363 patients treated with placebo for up to 16 weeks), infections were numerically highercompared to those observed in the psoriasis studies (30.7% of patients treated with secukinumabcompared with 31.7% in patients treated with placebo). Most of these were non-serious, mild ormoderate in severity and did not require treatment discontinuation or interruption.

In psoriasis phase III clinical studies, neutropenia was more frequently observed with secukinumabthan with placebo, but most cases were mild, transient and reversible. Neutropenia <1.0-0.5x109/l(CTCAE grade 3) was reported in 18 out of 3 430 (0.5%) patients on secukinumab, with no dosedependence and no temporal relationship to infections in 15 out of 18 cases. There were no reportedcases of more severe neutropenia. Non-serious infections with usual response to standard care and notrequiring discontinuation of secukinumab were reported in the remaining 3 cases.

The frequency of neutropenia in psoriatic arthritis, axial spondyloarthritis (ankylosing spondylitis andnon-radiographic axial spondyloarthritis) and hidradenitis suppurativa was similar to psoriasis.

Rare cases of neutropenia <0.5x109/l (CTCAE grade 4) were reported.

In psoriasis, psoriatic arthritis, axial spondyloarthritis (ankylosing spondylitis and non-radiographicaxial spondyloarthritis) and hidradenitis suppurativa clinical studies, less than 1% of patients treatedwith secukinumab developed antibodies to secukinumab up to 52 weeks of treatment. About half ofthe treatment-emergent anti-drug antibodies were neutralising, but this was not associated with loss ofefficacy or pharmacokinetic abnormalities.

Undesirable effects in paediatric patients from the age of 6 years with plaque psoriasis

The safety of secukinumab was assessed in two phase III studies in paediatric patients with plaquepsoriasis. The first study (paediatric study 1) was a double-blind, placebo-controlled study of162 patients from 6 to less than 18 years of age with severe plaque psoriasis. The second study(paediatric study 2) is an open-label study of 84 patients from 6 to less than 18 years of age withmoderate to severe plaque psoriasis. The safety profile reported in these two studies was consistentwith the safety profile reported in adult plaque psoriasis patients.

Undesirable effects in paediatric patients with JIA

The safety of secukinumab was also assessed in a phase III study in 86 juvenile idiopathic arthritispatients with ERA and JPsA from 2 to less than 18 years of age. The safety profile reported in thisstudy was consistent with the safety profile reported in adult patients.

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.

Doses up to 30 mg/kg (approximately 2000 to 3000 mg) have been administered intravenously inclinical studies without dose-limiting toxicity. In the event of overdose, it is recommended that thepatient be monitored for any signs or symptoms of adverse reactions and appropriate symptomatictreatment be instituted immediately.

Pharmacotherapeutic group: Immunosuppressants, interleukin inhibitors, ATC code: L04AC10

Secukinumab is a fully human IgG1/κ monoclonal antibody that selectively binds to and neutralisesthe proinflammatory cytokine interleukin-17A (IL-17A). Secukinumab works by targeting IL-17A andinhibiting its interaction with the IL-17 receptor, which is expressed on various cell types includingkeratinocytes. As a result, secukinumab inhibits the release of proinflammatory cytokines, chemokinesand mediators of tissue damage and reduces IL-17A-mediated contributions to autoimmune andinflammatory diseases. Clinically relevant levels of secukinumab reach the skin and reduce localinflammatory markers. As a direct consequence treatment with secukinumab reduces erythema,induration and desquamation present in plaque psoriasis lesions.

IL-17A is a naturally occurring cytokine that is involved in normal inflammatory and immuneresponses. IL-17A plays a key role in the pathogenesis of plaque psoriasis, psoriatic arthritis and axialspondyloarthritis (ankylosing spondylitis and non-radiographic axial spondyloarthritis) and isup-regulated in lesional skin in contrast to non-lesional skin of plaque psoriasis patients and insynovial tissue of psoriatic arthritis patients. The frequency of IL-17-producing cells was alsosignificantly higher in the subchondral bone marrow of facet joints from patients with ankylosingspondylitis. Increased numbers of IL-17A producing lymphocytes have also been found in patientswith non-radiographic axial spondyloarthritis. Inhibition of IL-17A was shown to be effective in thetreatment of ankylosing spondylitis, thus establishing the key role of this cytokine in axialspondyloarthritis.

Serum levels of total IL-17A (free and secukinumab-bound IL-17A) are initially increased in patientsreceiving secukinumab. This is followed by a slow decrease due to reduced clearance ofsecukinumab-bound IL-17A, indicating that secukinumab selectively captures free IL-17A, whichplays a key role in the pathogenesis of plaque psoriasis.

In a study with secukinumab, infiltrating epidermal neutrophils and various neutrophil-associatedmarkers that are increased in lesional skin of plaque psoriasis patients were significantly reduced afterone to two weeks of treatment.

Secukinumab has been shown to lower (within 1 to 2 weeks of treatment) levels of C-reactive protein,which is a marker of inflammation.

Adult plaque psoriasis

The safety and efficacy of secukinumab were assessed in four randomised, double-blind,placebo-controlled phase III studies in patients with moderate to severe plaque psoriasis who werecandidates for phototherapy or systemic therapy [ERASURE, FIXTURE, FEATURE, JUNCTURE].

The efficacy and safety of secukinumab 150 mg and 300 mg were evaluated versus either placebo oretanercept. In addition, one study assessed a chronic treatment regimen versus a “retreatment asneeded” regimen [SCULPTURE].

Of the 2 403 patients who were included in the placebo-controlled studies, 79% were biologic-naive,45% were non-biologic failures and 8% were biologic failures (6% were anti-TNF failures, and 2%were anti-p40 failures). Approximately 15 to 25% of patients in phase III studies had psoriatic arthritis(PsA) at baseline.

Psoriasis study 1 (ERASURE) evaluated 738 patients. Patients randomised to secukinumab received150 mg or 300 mg doses at weeks 0, 1, 2, 3 and 4, followed by the same dose every month. Psoriasisstudy 2 (FIXTURE) evaluated 1 306 patients. Patients randomised to secukinumab received 150 mg or300 mg doses at weeks 0, 1, 2, 3 and 4, followed by the same dose every month. Patients randomisedto etanercept received 50 mg doses twice per week for 12 weeks followed by 50 mg every week. Inboth study 1 and study 2, patients randomised to receive placebo who were non-responders at week 12then crossed over to receive secukinumab (either 150 mg or 300 mg) at weeks 12, 13, 14, and 15,followed by the same dose every month starting at week 16. All patients were followed for up to52 weeks following first administration of study treatment.

Psoriasis study 3 (FEATURE) evaluated 177 patients using a pre-filled syringe compared with placeboafter 12 weeks of treatment to assess the safety, tolerability, and usability of secukinumabself-administration via the pre-filled syringe. Psoriasis study 4 (JUNCTURE) evaluated 182 patientsusing a pre-filled pen compared with placebo after 12 weeks of treatment to assess the safety,tolerability, and usability of secukinumab self-administration via the pre-filled pen. In both study 3and study 4, patients randomised to secukinumab received 150 mg or 300 mg doses at weeks 0, 1, 2, 3and 4, followed by the same dose every month. Patients were also randomised to receive placebo atweeks 0, 1, 2, 3 and 4, followed by the same dose every month.

Psoriasis study 5 (SCULPTURE) evaluated 966 patients. All patients received secukinumab 150 mg or300 mg doses at weeks 0, 1, 2, 3, 4, 8 and 12 and then were randomised to receive either amaintenance regimen of the same dose every month starting at week 12 or a “retreatment as needed”regimen of the same dose. Patients randomised to “retreatment as needed” did not achieve adequatemaintenance of response and therefore a fixed monthly maintenance regimen is recommended.

The co-primary endpoints in the placebo and active-controlled studies were the proportion of patientswho achieved a PASI 75 response and IGA mod 2011 “clear” or “almost clear” response versusplacebo at week 12 (see Tables 4 and 5). The 300 mg dose provided improved skin clearanceparticularly for “clear” or “almost clear” skin across the efficacy endpoints of PASI 90, PASI 100, and

IGA mod 2011 0 or 1 response across all studies with peak effects seen at week 16, therefore this doseis recommended.

Table 4 Summary of PASI 50/75/90/100 & IGA⃰ mod 2011 “clear” or “almost clear” clinicalresponse in psoriasis studies 1, 3 and 4 (ERASURE, FEATURE and JUNCTURE)

Week 12 Week 16 Week 52

Placebo 150 mg 300 mg 150 mg 300 mg 150 mg 300 mg

Study 1

Number of patients 246 244 245 244 245 244 245

PASI 50 response n (%) 22 203 222 212 224 187 207(8.9%) (83.5%) (90.6%) (87.2%) (91.4%) (77%) (84.5%)

PASI 75 response n (%) 11 174 200 188 211 146 182(4.5%) (71.6%)** (81.6%)** (77.4%) (86.1%) (60.1%) (74.3%)

PASI 90 response n (%) 3 (1.2%) 95 145 130 171 88 147(39.1%)** (59.2%)** (53.5%) (69.8%) (36.2%) (60.0%)

PASI 100 response n (%) 2 (0.8%) 31 70 51 102 49 96(12.8%) (28.6%) (21.0%) (41.6%) (20.2%) (39.2%)

IGA mod 2011 “clear” or 6 125 160 142 180 101 148“almost clear” response (2.40%) (51.2%)** (65.3%)** (58.2%) (73.5%) (41.4%) (60.4%)n (%)

Study 3

Number of patients 59 59 58 - - - -

PASI 50 response n (%) 3 (5.1%) 51 51 - - - -(86.4%) (87.9%)

PASI 75 response n (%) 0 (0.0%) 41 44 - - - -(69.5%)** (75.9%)**

PASI 90 response n (%) 0 (0.0%) 27 35 - - - -(45.8%) (60.3%)

PASI 100 response n (%) 0 (0.0%) 5 25 - - - -(8.5%) (43.1%)

IGA mod 2011 “clear” or 0 (0.0%) 31 40 - - - -“almost clear” response (52.5%)** (69.0%)**n (%)

Study 4

Number of patients 61 60 60 - - - -

PASI 50 response n (%) 5 (8.2%) 48 58 - - - -(80.0%) (96.7%)

PASI 75 response n (%) 2 (3.3%) 43 52 - - - -(71.7%)** (86.7%)**

PASI 90 response n (%) 0 (0.0%) 24 33 - - - -(40.0%) (55.0%)

PASI 100 response n(%) 0 (0.0%) 10 16 - - - -(16.7%) (26.7%)

IGA mod 2011 “clear” or 0 (0.0%) 32 44 - - - -“almost clear” response (53.3%)** (73.3%)**n (%)

* The IGA mod 2011 is a 5-category scale including “0 = clear”, “1 = almost clear”, “2 = mild”, “3 =moderate” or “4 = severe”, indicating the physician’s overall assessment of the psoriasis severity focusingon induration, erythema and scaling. Treatment success of “clear” or “almost clear” consisted of no signs ofpsoriasis or normal to pink colouration of lesions, no thickening of the plaque and none to minimal focalscaling.

** p-values versus placebo and adjusted for multiplicity: p<0.0001.

Table 5 Summary of clinical response on psoriasis study 2 (FIXTURE)

Week 12 Week 16 Week 52

Placebo 150 mg 300 mg Etanercept 150 mg 300 mg Etanercept 150 mg 300 mg Etanercept

Number of 324 327 323 323 327 323 323 327 323 323patients

PASI 50 49 266 296 226 290 302 257 (79.6%) 249 274 234 (72.4%)response (15.1%) (81.3%) (91.6%) (70.0%) (88.7%) (93.5%) (76.1%) (84.8%)n (%)

PASI 75 16 219 249 142 247 280 189 (58.5%) 215 254 179 (55.4%)response (4.9%) (67.0%) (77.1%) (44.0%) (75.5%) (86.7%) (65.7%) (78.6%)n (%) ** **

PASI 90 5 (1.5%) 137 175 67 (20.7%) 176 234 101 (31.3%) 147 210 108 (33.4%)response (41.9%) (54.2%) (53.8%) (72.4%) (45.0%) (65.0%)n (%)

PASI 100 0 (0%) 47 78 14 (4.3%) 84 119 24 (7.4%) 65 117 32 (9.9%)response (14.4%) (24.1%) (25.7%) (36.8%) (19.9%) (36.2%)n (%)

IGA mod 9 (2.8%) 167 202 88 (27.2%) 200 244 127 (39.3%) 168 219 120 (37.2%)2011 “clear” (51.1%) (62.5%) (61.2%) (75.5%) (51.4%) (67.8%)or “almost ** **clear”responsen (%)

** p-values versus etanercept: p=0.0250

In an additional psoriasis study (CLEAR) 676 patients were evaluated. Secukinumab 300 mg met theprimary and secondary endpoints by showing superiority to ustekinumab based on PASI 90 responseat week 16 (primary endpoint), speed of onset of PASI 75 response at week 4, and long-term PASI 90response at week 52. Greater efficacy of secukinumab compared to ustekinumab for the endpoints

PASI 75/90/100 and IGA mod 2011 0 or 1 response (“clear” or “almost clear”) was observed earlyand continued through to week 52 (Table 6).

Table 6 Summary of clinical response on CLEAR study

Week 4 Week 16 Week 52

Secukinumab Ustekinumab* Secukinumab Ustekinumab* Secukinumab Ustekinumab*300 mg 300 mg 300 mg

Number of 334 335 334 335 334 335patients

PASI 75 166 (49.7%)** 69 (20.6%) 311 (93.1%) 276 (82.4%) 306 (91.6%) 262 (78.2%)response n (%)

PASI 90 70 (21.0%) 18 (5.4%) 264 (79.0%)** 192 (57.3%) 250 203 (60.6%)response n (%) (74.9%)***

PASI 100 14 (4.2%) 3 (0.9%) 148 (44.3%) 95 (28.4%) 150 (44.9%) 123 (36.7%)response n (%)

IGA mod 2011 128 (38.3%) 41 (12.2%) 278 (83.2%) 226 (67.5%) 261 (78.1%) 213 (63.6%)“clear” or“almost clear”response n (%)

* Patients treated with secukinumab received 300 mg doses at weeks 0, 1, 2 3 and 4, followed by the same doseevery 4 weeks until week 52. Patients treated with ustekinumab received 45 mg or 90 mg at weeks 0 and 4, thenevery 12 weeks until week 52 (dosed by weight as per approved posology)

** p-values versus ustekinumab: p<0.0001 for primary endpoint of PASI 90 at week 16 and secondary endpoint of PASI 75at week 4

*** p-values versus ustekinumab: p=0.0001 for secondary endpoint of PASI 90 at week 52

Secukinumab was efficacious in systemic treatment-naive, biologic-naive, biologic/anti-TNF-exposedand biologic/anti-TNF-failure patients. Improvements in PASI 75 in patients with concurrent psoriaticarthritis at baseline were similar to those in the overall plaque psoriasis population.

Secukinumab was associated with a fast onset of efficacy with a 50% reduction in mean PASI byweek 3 for the 300 mg dose.

Figure 1 Time course of percentage change from baseline of mean PASI score in study 1(ERASURE)

PASI % changefrom baseline

Weeks of treatmentn = number of patients evaluable

* secukinumab 150 mg (n=243) secukinumab 300 mg (n=245) Placebo (n=245)

Specific locations/forms of plaque psoriasis

In two additional placebo-controlled studies, improvement was seen in both nail psoriasis(TRANSFIGURE, 198 patients) and palmoplantar plaque psoriasis (GESTURE, 205 patients). In the

TRANSFIGURE study, secukinumab was superior to placebo at week 16 (46.1% for 300 mg, 38.4%for 150 mg and 11.7% for placebo) as assessed by significant improvement from baseline in the Nail

Psoriasis Severity Index (NAPSI %) for patients with moderate to severe plaque psoriasis with nailinvolvement. In the GESTURE study, secukinumab was superior to placebo at week 16 (33.3% for300 mg, 22.1% for 150 mg, and 1.5% for placebo) as assessed by significant improvement of ppIGA 0or 1 response (“clear” or “almost clear”) for patients with moderate to severe palmoplantar plaquepsoriasis.

A placebo-controlled study evaluated 102 patients with moderate to severe scalp psoriasis, defined ashaving a Psoriasis Scalp Severity Index (PSSI) score of ≥12, an IGA mod 2011 scalp only score of 3or greater and at least 30% of the scalp surface area affected. Secukinumab 300 mg was superior toplacebo at week 12 as assessed by significant improvement from baseline in both the PSSI 90 response(52.9% versus 2.0%) and IGA mod 2011 0 or 1 scalp only response (56.9% versus 5.9%).

Improvement in both endpoints was sustained for secukinumab patients who continued treatmentthrough to week 24.

Quality of life/patient-reported outcomes

Statistically significant improvements at week 12 (studies 1-4) from baseline compared to placebowere demonstrated in the DLQI (Dermatology Life Quality Index). Mean decreases (improvements) in

DLQI from baseline ranged from -10.4 to -11.6 with secukinumab 300 mg, from -7.7 to -10.1 withsecukinumab 150 mg, versus -1.1 to -1.9 for placebo at week 12. These improvements weremaintained for 52 weeks (studies 1 and 2).

Forty percent of the participants in studies 1 and 2 completed the Psoriasis Symptom Diary©. For theparticipants completing the diary in each of these studies, statistically significant improvements atweek 12 from baseline compared to placebo in patient-reported signs and symptoms of itching, painand scaling were demonstrated.

Statistically significant improvements at week 4 from baseline in patients treated with secukinumabcompared to patients treated with ustekinumab (CLEAR) were demonstrated in the DLQI and theseimprovements were maintained for up to 52 weeks.

Statistically significant improvements in patient-reported signs and symptoms of itching, pain andscaling at week 16 and week 52 (CLEAR) were demonstrated in the Psoriasis Symptom Diary© inpatients treated with secukinumab compared to patients treated with ustekinumab.

Statistically significant improvements (decreases) at week 12 from baseline in the scalp psoriasis studywere demonstrated in patient reported signs and symptoms of scalp itching, pain and scaling comparedto placebo.

Secukinumab has been shown to improve signs and symptoms, and health-related quality of life inpaediatric patients 6 years and older with plaque psoriasis (see Tables 8 and 10).

Severe plaque psoriasis

The safety and efficacy of secukinumab were assessed in a randomised, double-blind, placebo andetanercept-controlled phase III study in paediatric patients from 6 to <18 years of age with severeplaque psoriasis, as defined by a PASI score ≥20, an IGA mod 2011 score of 4, and BSA involvementof ≥10%, who were candidates for systemic therapy. Approximately 43% of the patients had priorexposure to phototherapy, 53% to conventional systemic therapy, 3% to biologics, and 9% hadconcomitant psoriatic arthritis.

The paediatric psoriasis study 1 evaluated 162 patients who were randomised to receive low dosesecukinumab (75 mg for body weight <50 kg or 150 mg for body weight ≥50 kg), high dosesecukinumab (75 mg for body weight <25 kg, 150 mg for body weight between ≥25 kg and <50 kg, or300 mg for body weight ≥50 kg), or placebo at weeks 0, 1, 2, 3, and 4 followed by the same doseevery 4 weeks, or etanercept. Patients randomised to etanercept received 0.8 mg/kg weekly (up to amaximum of 50 mg). Patient distribution by weight and age at randomisation is described in Table 7.

Table 7 Patient distribution by weight and age for paediatric psoriasis study 1

Randomisation Description Secukinumab Secukinumab Placebo Etanercept Totalstrata low dose high dosen=40 n=40 n=41 n=41 N=162

Age 6-<12 years 8 9 10 10 37≥12- 32 31 31 31 125<18 years

Weight <25 kg 2 3 3 4 12≥25-<50 kg 17 15 17 16 65≥50 kg 21 22 21 21 85

Patients randomised to receive placebo who were non-responders at week 12 were switched to eitherthe secukinumab low or high dose group (dose based on body weight group) and received study drugat weeks 12, 13, 14, and 15, followed by the same dose every 4 weeks starting at week 16. The co-primary endpoints were the proportion of patients who achieved a PASI 75 response and IGA mod2011 ‘clear’ or ‘almost clear’ (0 or 1) response at week 12.

During the 12 week placebo-controlled period, the efficacy of both the low and the high dose ofsecukinumab was comparable for the co-primary endpoints. The odds ratio estimates in favour of bothsecukinumab doses were statistically significant for both the PASI 75 and IGA mod 2011 0 or 1responses.

All patients were followed for efficacy and safety during the 52 weeks following the first dose. Theproportion of patients achieving PASI 75 and IGA mod 2011 ‘clear’ or ‘almost clear’ (0 or 1)responses showed separation between secukinumab treatment groups and placebo at the first post-baseline visit at week 4, the difference becoming more prominent at week 12. The response wasmaintained throughout the 52 week time period (see Table 8). Improvement in PASI 50, 90, 100responder rates and Children’s Dermatology Life Quality Index (CDLQI) scores of 0 or 1 were alsomaintained throughout the 52 week time period.

In addition, PASI 75, IGA 0 or 1, PASI 90 response rates at weeks 12 and 52 for both secukinumablow and high dose groups were higher than the rates for patients treated with etanercept (see Table 8).

Beyond week 12, efficacy of both the low and the high dose of secukinumab was comparable althoughthe efficacy of the high dose was higher for patients ≥50 kg. The safety profiles of the low dose andthe high dose were comparable and consistent with the safety profile in adults.

Table 8 Summary of clinical response in severe paediatric psoriasis at weeks 12 and 52(paediatric psoriasis study 1)*

Response Treatment comparison 'test' 'control' odds ratiocriterion 'test' vs. 'control' n**/m (%) n**/m (%) estimate (95% CI) p-value

At week 12***

PASI 75 secukinumab low dose vs. placebo 32/40 (80.0) 6/41 (14.6) 25.78 (7.08, 114.66) <0.0001secukinumab high dose vs. placebo 31/40 (77.5) 6/41 (14.6) 22.65 (6.31, 98.93) <0.0001secukinumab low dose vs. etanercept 32/40 (80.0) 26/41 (63.4) 2.25 (0.73, 7.38)secukinumab high dose vs. etanercept 31/40 (77.5) 26/41 (63.4) 1.92 (0.64, 6.07)

IGA 0/1 secukinumab low dose vs. placebo 28/40 (70.0) 2/41 (4.9) 51.77 (10.02, 538.64) <0.0001secukinumab high dose vs. placebo 24/40 (60.0) 2/41 (4.9) 32.52 (6.48, 329.52) <0.0001secukinumab low dose vs. etanercept 28/40 (70.0) 14/41 (34.1) 4.49 (1.60, 13.42)secukinumab high dose vs. etanercept 24/40 (60.0) 14/41 (34.1) 2.86 (1.05, 8.13)

PASI 90 secukinumab low dose vs. placebo 29/40 (72.5) 1/41 (2.4) 133.67 (16.83, 6395.22) <0.0001secukinumab high dose vs. placebo 27/40 (67.5) 1/41 (2.4) 102.86 (13.22, 4850.13) <0.0001secukinumab low dose vs. etanercept 29/40 (72.5) 12/41 (29.3) 7.03 (2.34, 23.19)secukinumab high dose vs. etanercept 27/40 (67.5) 12/41 (29.3) 5.32 (1.82, 16.75)

At week 52

PASI 75 secukinumab low dose vs. etanercept 35/40 (87.5) 28/41 (68.3) 3.12 (0.91, 12.52)secukinumab high dose vs. etanercept 35/40 (87.5) 28/41 (68.3) 3.09 (0.90, 12.39)

IGA 0/1 secukinumab low dose vs. etanercept 29/40 (72.5) 23/41 (56.1) 2.02 (0.73, 5.77)secukinumab high dose vs. etanercept 30/40 (75.0) 23/41 (56.1) 2.26 (0.81, 6.62)

PASI 90 secukinumab low dose vs. etanercept 30/40 (75.0) 21/41 (51.2) 2.85 (1.02, 8.38)secukinumab high dose vs. etanercept 32/40 (80.0) 21/41 (51.2) 3.69 (1.27, 11.61)

* non-responder imputation was used to handle missing values

** n is the number of responders, m = number of patients evaluable

*** extended visit window at week 12

Odds ratio, 95% confidence interval, and p-value are from an exact logistic regression model with treatmentgroup, baseline body-weight category and age category as factors

A higher proportion of paediatric patients treated with secukinumab reported improvement in health-related quality of life as measured by a CDLQI score of 0 or 1 compared to placebo at week 12 (lowdose 44.7%, high dose 50%, placebo 15%). Over time up to and including week 52 both secukinumabdose groups were numerically higher than the etanercept group (low dose 60.6%, high dose 66.7%,etanercept 44.4%).

Moderate to severe plaque psoriasis

Secukinumab was predicted to be effective for the treatment of paediatric patients with moderateplaque psoriasis based on the demonstrated efficacy and exposure response relationship in adultpatients with moderate to severe plaque psoriasis, and the similarity of the disease course,pathophysiology, and drug effect in adult and paediatric patients at the same exposure levels.

Moreover, the safety and efficacy of secukinumab was assessed in an open-label, two-arm,parallel-group, multicentre phase III study in paediatric patients from 6 to <18 years of age withmoderate to severe plaque psoriasis, as defined by a PASI score ≥12, an IGA mod 2011 score of ≥3,and BSA involvement of ≥10%, who were candidates for systemic therapy.

The paediatric psoriasis study 2 evaluated 84 patients who were randomised to receive low dosesecukinumab (75 mg for body weight <50 kg or 150 mg for body weight ≥50 kg) or high dosesecukinumab (75 mg for body weight <25 kg, 150 mg for body weight between ≥25 kg and <50 kg, or300 mg for body weight ≥50 kg) at weeks 0, 1, 2, 3, and 4 followed by the same dose every 4 weeks.

Patient distribution by weight and age at randomisation is described in Table 9.

Table 9 Patient distribution by weight and age for paediatric psoriasis study 2

Sub-groups Description Secukinumab Secukinumab Totallow dose high dosen=42 n=42 N=84

Age 6-<12 years 17 16 33≥12-<18 years 25 26 51

Weight <25 kg 4 4 8≥25-<50 kg 13 12 25≥50 kg 25 26 51

The co-primary endpoints were the proportion of patients who achieved a PASI 75 response and IGAmod 2011 ‘clear’ or ‘almost clear’ (0 or 1) response at week 12.

The efficacy of both the low and the high dose of secukinumab was comparable and showedstatistically significant improvement compared to historical placebo for the co-primary endpoints. Theestimated posterior probability of a positive treatment effect was 100%.

Patients were followed for efficacy over a 52 week period after first administration. Efficacy (definedas PASI 75 response and IGA mod 2011 ‘clear’ or ‘almost clear’ [0 or 1]) was observed as early as thefirst post-baseline visit at week 2, and the proportion of patients who achieved a PASI 75 response and

IGA mod 2011 ‘clear’ or ‘almost clear’ (0 or 1) increased up to week 24 and were sustained untilweek 52. Improvement in PASI 90 and PASI 100 were also observed at week 12, increased up toweek 24, and were sustained until week 52 (see Table 10).

The safety profiles of the low dose and the high dose were comparable and consistent with the safetyprofile in adults.

Table 10 Summary of clinical response in moderate to severe paediatric psoriasis at weeks 12and 52 (paediatric psoriasis study 2)*

Week 12 Week 52

Secukinumab Secukinumab Secukinumab Secukinumablow dose high dose low dose high dose

Number of patients 42 42 42 42

PASI 75 response n (%) 39 (92.9%) 39 (92.9%) 37 (88.1%) 38 (90.5%)

IGA mod 2011 ‘clear’ or ‘almost 33 (78.6%) 35 (83.3%) 36 (85.7%) 35 (83.3%)clear’ response n (%)

PASI 90 response n (%) 29 (69%) 32 (76.2%) 32 (76.2%) 35 (83.3%)

PASI 100 response n (%) 25 (59.5%) 23 (54.8%) 22 (52.4%) 29 (69.0%)

* non-responder imputation was used to handle missing values

These outcomes in the paediatric moderate to severe plaque psoriasis population confirmed thepredictive assumptions based on the efficacy and exposure response relationship in adult patients,mentioned above.

In the low dose group, 50% and 70.7% of patients achieved a CDLQI 0 or 1 score at weeks 12 and 52,respectively. In the high dose group, 61.9% and 70.3% achieved a CDLQI 0 or 1 score at weeks 12and 52, respectively.

Enthesitis-related arthritis (ERA) and juvenile psoriatic arthritis (JPsA)

The efficacy and safety of secukinumab were assessed in 86 patients in a 3-part, double-blind,placebo-controlled, event-driven, randomised, phase III study in patients 2 to <18 years of age withactive ERA or JPsA as diagnosed based on a modified International League of Associations for

Rheumatology (ILAR) JIA classification criteria. The study consisted of an open-label portion (Part 1)where all patients received secukinumab until week 12. Patients demonstrating a JIA ACR 30response at week 12 entered into the Part 2 double-blind phase and were randomised 1:1 to continuetreatment with secukinumab or to begin treatment with placebo (randomised withdrawal) untilweek 104 or until a flare occured. Patients who flared then entered open-label secukinumab treatmentuntil week 104 (Part 3).

The JIA patient subtypes at study entry were: 60.5% ERA and 39.5% JPsA, who either had inadequateresponse or were intolerant to ≥1 disease-modifying antirheumatic drugs (DMARDs) and ≥1 non-steroidal anti-inflammatory drugs (NSAIDs). At baseline, MTX use was reported for 65.1% ofpatients; (63.5% [33/52] of ERA patients and 67.6% [23/34] of JPsA patients). There were 12 out of52 ERA patients concomitantly treated with sulfasalazine (23.1%). Patients with a body weight atbaseline <50 kg (n=30) were given a dose of 75 mg and patients with a body weight ≥50 kg (n=56)were given a dose of 150 mg. Age at baseline ranged from 2 to 17 years, with 3 patients between 2 to<6 years, 22 patients 6 to <12 years and 61 patients 12 to <18 years. At baseline the Juvenile Arthritis

Disease Activity Score (JADAS)-27 was 15.1 (SD:7.1).

The primary endpoint was time to flare in the randomised withdrawal period (Part 2). Disease flarewas defined as a ≥30% worsening in at least three of the six JIA ACR response criteria and ≥30%improvement in not more than one of the six JIA ACR response criteria and a minimum of two activejoints.

At the end of Part 1, 75 out of 86 (87.2%) patients demonstrated a JIA ACR 30 response and enteredinto Part 2.

The study met its primary endpoint by demonstrating a statistically significant prolongation in the timeto disease flare in patients treated with secukinumab compared to placebo in Part 2. The risk of flarewas reduced by 72% for patients on secukinumab compared with patients on placebo in Part 2 (Hazardratio=0.28, 95% CI: 0.13 to 0.63, p<0.001) (Figure 2 and Table 11). During Part 2, a total of21 patients in the placebo group experienced a flare event (11 JPsA and 10 ERA) compared with10 patients in the secukinumab group (4 JPsA and 6 ERA).

Figure 2 Kaplan-Meier estimates of the time to disease flare in Part 2

Proportion ofpatients withdisease flare (%)

Time (days)

Secukinumab ------ Placebo in Part 2 + Censored

Number of patients at risk

Secukinumab 37 36 34 33 32 30 30 29 29 29 25 25 24 23 23 23 23 23 23 21 21 21 20 14 0

Placebo in Part 2 38 38 32 29 28 25 22 21 21 21 20 20 19 19 19 18 18 16 16 15 15 15 15 10 0

Table 11 Survival analysis of time to disease flare - Part 2

Secukinumab Placebo in Part 2(N=37) (N=38)

Number of flare events at the end of Part 2, 10 (27.0) 21 (55.3)n (%)

Kaplan-Meier estimates:

Median, in days (95% CI) NC (NC, NC) 453.0 (114.0, NC)

Flare-free rate at 6 months (95% CI) 85.8 (69.2, 93.8) 60.1 (42.7, 73.7)

Flare-free rate at 12 months (95% CI) 76.7 (58.7, 87.6) 54.3 (37.1, 68.7)

Flare-free rate at 18 months (95% CI) 73.2 (54.6, 85.1) 42.9 (26.7, 58.1)

Hazard ratio to placebo: Estimate (95% CI) 0.28 (0.13, 0.63)

Stratified log-rank test p-value <0.001**

Analysis was conducted on all randomised patients who received at least one dose of study drug in

Part 2.

Secukinumab: all patients who did not take any placebo. Placebo in Part 2: all patients who tookplacebo in Part 2 and secukinumab in other period/s. NC = Not calculable. ** = Statisticallysignificant on one-sided significance level 0.025.

In open-label Part 1, all patients received secukinumab until week 12. At week 12, 83.7%, 67.4%, and38.4% of children were JIA ACR 50, 70 and 90 responders, respectively (Figure 3). The onset ofaction of secukinumab occurred as early as week 1. At week 12 the JADAS-27 score was 4.64(SD:4.73) and the mean decrease from baseline in JADAS-27 was -10.487 (SD:7.23).

Figure 3 JIA ACR 30/50/70/90 response for subjects up to week 12 in Part 1*

Percentage ofresponders

Time (weeks)

*non-responder imputation was used to handle missing values

The data in the 2 to <6 age group were inconclusive due to the low number of patients below 6 yearsof age enrolled in the study.

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

Cosentyx in plaque psoriasis in paediatric patients aged from birth to less than 6 years and in chronicidiopathic arthritis for paediatric patients aged from birth to less than 2 years (see section 4.2 forinformation on paediatric use).

Most pharmacokinetics properties observed in patients with plaque psoriasis, psoriatic arthritis andankylosing spondylitis were similar.

Plaque psoriasis

In a pool of the two paediatric studies, patients with moderate to severe plaque psoriasis (6 to less than18 years of age) were administered secukinumab at the recommended paediatric dosing regimen. Atweek 24, patients weighing ≥25 and <50 kg had a mean ± SD steady-state trough concentration of19.8±6.96 µg/ml (n=24) after 75 mg of secukinumab and patients weighing ≥50 kg had mean ±SDtrough concentration of 27.3±10.1 µg/ml (n=36) after 150 mg of secukinumab. The mean ± SDsteady-state trough concentration in patients weighing <25 kg (n=8) was 32.6±10.8 µg/ml at week 24after 75 mg dose.

In a paediatric study, ERA and JPsA patients (2 to less than 18 years of age) were administeredsecukinumab at the recommended paediatric dosing regimen. At week 24, patients weighing <50 kg,and weighing ≥50 kg had a mean ± SD steady-state trough concentration of 25.2±5.45 µg/ml (n=10)and 27.9±9.57 µg/ml (n=19), respectively.

Adult population

Following a single subcutaneous dose of 300 mg as a liquid formulation in healthy volunteers,secukinumab reached peak serum concentrations of 43.2±10.4 μg/ml between 2 and 14 days post dose.

Based on population pharmacokinetic analysis, following a single subcutaneous dose of either 150 mgor 300 mg in plaque psoriasis patients, secukinumab reached peak serum concentrations of13.7±4.8 µg/ml or 27.3±9.5 µg/ml, respectively, between 5 and 6 days post dose.

After initial weekly dosing during the first month, time to reach the maximum concentration wasbetween 31 and 34 days based on population pharmacokinetic analysis.

On the basis of simulated data, peak concentrations at steady-state (Cmax,ss) following subcutaneousadministration of 150 mg or 300 mg were 27.6 µg/ml and 55.2 µg/ml, respectively. Populationpharmacokinetic analysis suggests that steady-state is reached after 20 weeks with monthly dosingregimens.

Compared with exposure after a single dose, the population pharmacokinetic analysis showed thatpatients exhibited a 2-fold increase in peak serum concentrations and area under the curve (AUC)following repeated monthly dosing during maintenance.

Population pharmacokinetic analysis showed that secukinumab was absorbed with an average absolutebioavailability of 73% in patients with plaque psoriasis. Across studies, absolute bioavailabilities inthe range between 60 and 77% were calculated.

The bioavailability of secukinumab in PsA patients was 85% on the basis of the populationpharmacokinetic model.

Following a single subcutaneous injection of 300 mg solution for injection in pre-filled syringe inplaque psoriasis patients, secukinumab systemic exposure was similar to what was observedpreviously with two injections of 150 mg.

The mean volume of distribution during the terminal phase (Vz) following single intravenousadministration ranged from 7.10 to 8.60 litres in plaque psoriasis patients, suggesting thatsecukinumab undergoes limited distribution to peripheral compartments.

The majority of IgG elimination occurs via intracellular catabolism, following fluid-phase or receptormediated endocytosis.

Mean systemic clearance (CL) following a single intravenous administration to patients with plaquepsoriasis ranged from 0.13 to 0.36 l/day. In a population pharmacokinetic analysis, the mean systemicclearance (CL) was 0.19 l/day in plaque psoriasis patients. The CL was not impacted by gender.

Clearance was dose- and time-independent.

The mean elimination half-life, as estimated from population pharmacokinetic analysis, was 27 days inplaque psoriasis patients, ranging from 18 to 46 days across psoriasis studies with intravenousadministration.

The single and multiple dose pharmacokinetics of secukinumab in plaque psoriasis patients weredetermined in several studies with intravenous doses ranging from 1x 0.3 mg/kg to 3x 10 mg/kg andwith subcutaneous doses ranging from 1x 25 mg to multiple doses of 300 mg. Exposure was doseproportional across all dosing regimens.

No pharmacokinetic data are available in patients with renal or hepatic impairment. The renalelimination of intact secukinumab, an IgG monoclonal antibody, is expected to be low and of minorimportance. IgGs are mainly eliminated via catabolism and hepatic impairment is not expected toinfluence clearance of secukinumab.

Effect of weight on pharmacokinetics

Secukinumab clearance and volume of distribution increase as body weight increases.

Non-clinical data revealed no special hazard for humans (adult or paediatric) based on conventionalstudies of safety pharmacology, repeated dose and reproductive toxicity, or tissue cross-reactivity.

Animal studies have not been conducted to evaluate the carcinogenic potential of secukinumab.

Trehalose dihydrate

Histidine

Histidine hydrochloride monohydrate

Methionine

Polysorbate 80

Water for injections

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

2 years

If necessary, Cosentyx may be stored unrefrigerated for a single period of up to 4 days at roomtemperature, not above 30°C.

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

Store in the original package in order to protect from light.

Cosentyx 75 mg solution for injection in pre-filled syringe is supplied in a pre-filled 0.5 ml glasssyringe with a silicone-coated bromobutyl rubber plunger stopper, staked 27G x ½″ needle and rigidneedle shield of styrene butadiene rubber assembled in an automatic needle guard of polycarbonate.

Cosentyx 75 mg solution for injection in pre-filled syringe is available in unit packs containing1 pre-filled syringe and in multipacks containing 3 (3 packs of 1) pre-filled syringes.

Not all pack sizes may be marketed.

Cosentyx 75 mg solution for injection is supplied in a single-use pre-filled syringe for individual use.

The syringe should be taken out of the refrigerator 20 minutes before injecting to allow it to reachroom temperature.

Prior to use, a visual inspection of the pre-filled syringe is recommended. The liquid should be clear.

Its colour may vary from colourless to slightly yellow. You may see a small air bubble, which isnormal. Do not use if the liquid contains easily visible particles, is cloudy or is distinctly brown.

Detailed instructions for use are provided in the package leaflet.

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

Novartis Europharm Limited

Vista Building

Elm Park, Merrion Road

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Ireland

EU/1/14/980/012-013

Date of first authorisation: 15 January 2015

Date of latest renewal: 03 September 2019

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

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