COSENTYX

Main information

  • Trade name:
  • COSENTYX secukinumab (rch) 150 mg powder for injection vial
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • COSENTYX secukinumab (rch) 150 mg powder for injection vial
    Australia
  • Language:
  • English

Other information

Status

  • Source:
  • Dept. of Health,Therapeutic Goods Administration - Australia
  • Authorization number:
  • 218798
  • Last update:
  • 08-10-2017

Public Assessment Report

Public Summary

Summary for ARTG Entry:

218798

COSENTYX secukinumab (rch) 150 mg powder for injection vial

ARTG entry for

Medicine Registered

Sponsor

Novartis Pharmaceuticals Australia Pty Ltd

Postal Address

PO Box 101,NORTH RYDE, NSW, 1670

Australia

ARTG Start Date

12/01/2015

Product category

Medicine

Status

Active

Approval area

Drug Safety Evaluation Branch

Conditions

Conditions applicable to all therapeutic goods as specified in the document "Standard Conditions Applying to Registered or Listed Therapeutic Goods

Under Section 28 of the Therapeutic Goods Act 1989" effective 1 July 1995.

Conditions applicable to the relevant category and class of therapeutic goods as specified in the document "Standard Conditions Applying to Registered

or Listed Therapeutic Goods Under Section 28 of the Therapeutic Goods Act 1989" effective 1 July 1995.

Products

1. COSENTYX secukinumab (rch) 150 mg powder for injection vial

Product Type

Single Medicine Product

Effective date

29/05/2017

Warnings

See Product Information and Consumer Medicine Information for this product

Standard Indications

Specific Indications

Plaque psoriasis

COSENTYX is indicated for the treatment of moderate to severe plaque psoriasis in adult patients who are candidates for systemic therapy or

phototherapy.

Psoriatic arthritis

Cosentyx is indicated for the treatment of adult patients with active psoriatic arthritis when the response to previous disease-modifying anti-rheumatic

drug (DMARD) therapy has been inadequate

Ankylosing spondylitis

COSENTYX is indicated for the treatment of adult patients with active ankylosing spondylitis

Additional Product information

Container information

Type

Material

Life Time

Temperature

Closure

Conditions

Vial

Glass

36 Months

Store at 2 to 8

degrees Celsius

Child resistant closure

Store in Original

Container

Do not Freeze

Pack Size/Poison information

Pack Size

Poison Schedule

2 vials

(S4) Prescription Only Medicine

1 vial

(S4) Prescription Only Medicine

Components

1. COSENTYX secukinumab (rch) 150 mg powder for injection vial

Dosage Form

Injection, powder for

Route of Administration

Subcutaneous

Visual Identification

Colourless 6 mL glass vials, chlorobutyl rubber stopper with fluorocarbon

layer on the product side, aluminum cap with plastic flip off lid

Active Ingredients

Secukinumab

150 mg

© Commonwealth of Australia.This work is copyright.You are not permitted to re-transmit, distribute or commercialise the material without obtaining prior

written approval from the Commonwealth.Further details can be found at http://www.tga.gov.au/about/website-copyright.htm.

Public Summary

Page 1 of

Produced at 26.11.2017 at 04:29:00 AEDT

This is not an ARTG Certificate document.

The onus is on the reader to verify the current accuracy of the information on the document subsequent to the date shown.

Visit www.tga.gov.au for contact information

Summary of Product characteristics

Page 1 of 23

COSENTYX

secukinumab (rch)

NAME OF THE MEDICINE

Active ingredient:

Secukinumab

Chemical name:

Recombinant human monoclonal anti-human Interleukin-17A (IL-17A, IL-17)

antibody of the IgG1/kappa isotype

CAS Numbers:

875356-43-7 (heavy chain), 875356-44-8 (light chain)

Molecular formula:

6584

10134

1754

2042

Molecular weight:

Approximately 148 kDa

Structure:

The amino acid sequences of the light chain (215 amino acids) and the heavy

chain (457 amino acids) respectively.

DESCRIPTION

Secukinumab

recombinant

fully

human

monoclonal

antibody

selective

interleukin-17A.

Secukinumab is of the IgG1/κ-class produced in Chinese Hamster Ovary (CHO) cells.

Powder for injection

Each vial of powder for injection contains 150 mg of secukinumab as a lyophilised cake in glass vials.

Excipients: water for injections, sucrose, histidine, histidine hydrochloride monohydrate, polysorbate

Solution for injection

Solution for injection in a single-use, pre-filled syringe and/or pen (auto-injector).

Prefilled syringe

Each single-use pre-filled syringe contains 150 mg/mL of secukinumab. Excipients: trehalose dihydrate,

histidine, histidine hydrochloride monohydrate, polysorbate 80, methionine, water for injections.

Pen

Each single-use prefilled pen contains 150 mg/mL of secukinumab. Excipients: trehalose dihydrate,

histidine, histidine hydrochloride monohydrate, polysorbate 80, methionine, water for injections.

PHARMACOLOGY

Pharmacotherapeutic group: interleukin inhibitors; ATC Code: L04AC10

Mechanism of action

Secukinumab

fully

human

IgG1

antibody

that

selectively

binds

neutralises

proinflammatory cytokine interleukin-17A (IL-17A). IL-17A is a naturally occurring cytokine that is

involved in normal inflammatory and immune responses. IL-17A plays a key role in the pathogenesis

of plaque psoriasis, psoriatic arthritis, and ankylosing spondylitis. Increased numbers of IL-17A

producing lymphocytes and innate immune cells and increased levels of IL-17A have been found in the

blood of patients with plaque psoriasis, psoriatic arthritis, and ankylosing spondylitis and affected skin

of patients with plaque psoriasis. IL-17A is highly up-regulated in lesional skin in contrast to non-lesional

skin of plaque psoriasis patients. Higher frequency of IL-17- producing cells was detected in the synovial

fluid of patients with psoriatic arthritis and in the subchondral bone marrow of facet joints from patients

with ankylosing spondylitis. IL-17A also promotes tissue inflammation, neutrophil infiltration, bone and

tissue destruction, and tissue remodelling including angiogenesis and fibrosis.

Secukinumab works by targeting IL-17A and inhibiting its interaction with the IL-17 receptor, which is

expressed on various cell types including keratinocytes. As a result, secukinumab inhibits the release

of proinflammatory cytokines, chemokines and mediators of tissue damage and reduces IL-17A-

mediated

contributions

autoimmune

inflammatory

diseases.

Clinically

relevant

levels

secukinumab reach the skin and reduce local inflammatory markers. As a direct consequence,

Page 2 of 23

treatment with secukinumab reduces erythema, induration, and desquamation present in plaque

psoriasis lesions.

Pharmacodynamics

Serum levels of total IL-17A (free and secukinumab-bound IL-17A) are increased due to reduced

clearance of secukinumab-bound IL-17A within 2 to 7 days in patients receiving secukinumab, indicating

that secukinumab selectively captures free IL-17A which plays a key role in the pathogenesis of plaque

psoriasis.

In a study with secukinumab, infiltrating epidermal neutrophils and various neutrophil associated

markers that are increased in lesional skin of plaque psoriasis patients were significantly reduced after

one 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 in psoriatic arthritis and ankylosing spondylitis.

Pharmacokinetic properties

The mean pharmacokinetic parameters of secukinumab following single and multiple subcutaneous

administration in adult patients with psoriasis, resulting from population pharmacokinetic analysis, are

shown in Table 1. C

and AUC were dose-proportional at 150 mg and 300 mg subcutaneous doses.

Table 1

Summary of pharmacokinetic parameters of COSENTYX at steady – state following

150 or 300 mg s.c. administration in adult patients with psoriasis

Parameter

COSENTYX 4-weekly dose

150 mg

300 mg

Mean (SD)

Range

Mean (SD)

Range

Cmax,ss (µg/mL)

27.6 (10.7)

(13.7, 47.4)

55.2 (21.5)

(27.5, 94.8)

Cav,ss (µg/mL)

22.2 (9.2)

(10.5, 39.0

44.5 (18.4)

(21.1, 77.9)

Tmax,ss (day)

(4.0, 8.0)

(4.0, 8.0)

AUCss (day.µg/mL)

622 (257)

(295, 1090)

1245 (515)

(590, 2180)

Absorption

Following a single subcutaneous dose of either 150 mg or 300 mg in plaque psoriasis patients,

secukinumab reached peak serum concentrations of 13.7 ± 4.8 ug/mL or 27.3 ± 9.5 ug/mL, respectively,

between 5 to 6 days post dose.

After the initial weekly dosing during the first month, the time to reach the maximum concentration was

between 31 and 34 days.

Peak concentrations at steady-state (C

,ss) following subcutaneous administration of 150 mg or 300

mg were 27.6 ug/mL and 55.2 ug/mL, respectively. Steady-state is reached after 20 weeks with monthly

dosing regimens.

Compared with exposure after a single dose, patients exhibited a 2-fold increase in peak serum

concentrations and AUC following repeated monthly dosing during maintenance.

Secukinumab is absorbed with an average absolute bioavailability of 73%.

Distribution

The mean volume of distribution during the terminal phase (V

) following a single intravenous

administration ranged from 7.10 to 8.60 L in plaque psoriasis patients suggesting that secukinumab

undergoes limited distribution to peripheral compartments.

Secukinumab concentrations in interstitial fluid in the skin of plaque psoriasis patients ranged from 28

% to 39 % of those in serum at 1 and 2 weeks after a single subcutaneous dose of 300 mg secukinumab.

Metabolism

The metabolic pathway of secukinumab has not been characterised. As a human IgG1κ monoclonal

Page 3 of 23

antibody secukinumab is expected to be degraded into small peptides and amino acids via catabolic

pathways in the same manner as endogenous IgG.

Elimination

Mean systemic clearance (CL) was 0.19 L/d in plaque psoriasis patients. Clearance was dose- and

time-independent, as expected for a therapeutic IgG1 monoclonal antibody interacting with a soluble

cytokine target, such as IL-17A.

The mean elimination half-life was estimated to be 27 days in plaque psoriasis patients. Estimated half-

lives in individual plaque psoriasis patients range from 17 to 41 days.

Dose linearity

The single and multiple dose pharmacokinetics of secukinumab in plaque psoriasis patients were

determined in several studies with intravenous doses ranging from 1 x 0.3 mg/kg to 3 x 10 mg/kg and

with subcutaneous doses ranging from 1 x 25 mg to multiple doses of 300 mg. Exposure was dose

proportional across all dosing regimens.

The pharmacokinetics properties of secukinumab observed in psoriatic arthritis and ankylosing

spondylitis patients were similar to those displayed in plaque psoriasis patients. The bioavailability of

secukinumab in PsA patients was 85% on the basis of the population pharmacokinetic model.

Pharmacokinetics in special patient groups

Paediatrics (< 18 years of age)

Specific studies of COSENTYX in paediatric patients have not been conducted.

Elderly patients

Of the 3,430 plaque psoriasis patients exposed to COSENTYX in clinical studies, a total of 230 were

65 years of age or older and 32 patients were 75 years of age or older.

Of the 974 psoriatic arthritis patients exposed to COSENTYX in clinical studies, a total of 85 patients

were 65 years of age or older and 4 patients were 75 years of age or older.

Of the 571 ankylosing spondylitis patients exposed to COSENTYX in clinical studies, a total of 24

patients were 65 years of age or older and 3 patients were 75 years of age or older.

Based on population PK analysis, clearance in elderly patients and patients less than 65 years of age

was similar.

Patients with renal and hepatic impairment

No pharmacokinetic data are available in patients with hepatic or renal impairment.

Effect of weight on pharmacokinetics

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

CLINICAL TRIALS

Plaque psoriasis

The safety and

efficacy

COSENTYX

were evaluated versus placebo

etanercept

in four

randomised, double-blind, placebo-controlled phase 3 studies in adult patients with moderate to severe

chronic plaque-type psoriasis poorly controlled by topical treatments and / or phototherapy and / or

previous systemic therapy (ERASURE, FIXTURE, FEATURE, and JUNCTURE). The safety and

efficacy of COSENTYX were evaluated versus placebo or etanercept in four randomised, double-blind,

placebo-controlled phase 3 studies in patients with moderate to severe plaque psoriasis who were

candidates for phototherapy or systemic therapy (ERASURE, FIXTURE, FEATURE, and JUNCTURE).

In addition, one study assessed a chronic treatment regimen versus a ‘retreatment as needed’ regimen

(SCULPTURE). The co-primary endpoints in the placebo and active controlled studies were the

proportion of patients who achieved a PASI 75 response and IGA mod 2011 ’clear’ or ‘almost clear’

response versus placebo at Week 12.

Page 4 of 23

Key exclusion criteria across pivotal trials were: forms of psoriasis other than chronic plaque-type; drug-

induced psoriasis; ongoing use of certain psoriasis treatments, e.g. topical or systemic corticosteroids

or UV therapy; patients with active, ongoing inflammatory disease; patients with active, ongoing, chronic

or recurrent infectious disease; evidence of tuberculosis infection (enrolment was allowed for patients

with latent tuberculosis if appropriate treatment was initiated and maintained according to the local

treatment guideline); history of HIV, hepatitis B or hepatitis C; underlying immunocompromising

conditions; presence of lymphoproliferative disease, malignancy or history of malignancy within the past

5 years; significant medical problems including uncontrolled hypertension and congestive heart failure

(NYHA Class III and IV); patients with serum creatinine >176.8 micromol/L or with white blood cell count

<2,500 /microL, platelets <100,000/microL, neutrophils <1,500/microL or haemoglobin <8.5 g/dL;

pregnant or nursing women; and women of child-bearing potential not using effective contraception

during the study.

Of the 2,403 patients who were included in the placebo-controlled studies, 79 % were biologic-naïve,

45 % were non-biologic failures, 8 % were biologic failures, 6 % were anti-TNF failures, and 2 % were

anti-p40 failures. Baseline disease characteristics were generally consistent across all treatment groups

with a median baseline Psoriasis Area Severity Index (PASI) score from 19 to 20, IGA mod 2011

baseline score ranged from “moderate” (62 %) to “severe” (38 %), median baseline Body Surface Area

(BSA) ≥ 27 and median Dermatology Life Quality Index (DLQI) score from 10 to 12. Approximately 15

to 25 % of patients in phase III studies had psoriatic arthritis (PsA) at baseline.

ERASURE Study (A2302)

This trial evaluated 738 patients. Patients were randomised to COSENTYX received 150 mg or 300 mg

doses at weeks 0, 1, 2, and 3, followed by the same dose every month starting at week 4. Patients were

randomised to receive placebo who were non-responders at week 12 were then crossed over to receive

COSENTYX (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 to 52 weeks following first administration of

study treatment.

FIXTURE Study (A2303)

This trial evaluated 1,306 patients. Patients were randomised to COSENTYX received 150 mg or 300

mg doses at weeks 0, 1, 2, and 3, followed by the same dose every month starting at week 4. Patients

were randomised to etanercept received 50 mg doses twice per week for 12 weeks followed by 50 mg

every week. Patients were randomised to receive placebo who were non-responders at week 12 then

crossed over to receive COSENTYX (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 to 52 weeks

following first administration of study treatment.

FEATURE Study (A2308)

This trial evaluated 177 patients using a pre-filled syringe compared with placebo after 12 weeks of

treatment to assess the safety, tolerability, and usability of COSENTYX self-administration via the pre-

filled syringe. Patients randomised to COSENTYX received 150 mg or 300 mg doses at weeks 0, 1, 2,

and 3, followed by the same dose every month starting at week 4. Patients were also randomised to

receive placebo at weeks 0, 1, 2, and 3, followed by the same dose every month starting at week 4.

JUNCTURE Study (A2309)

This trial evaluated 182 patients using a pre-filled pen compared with placebo after 12 weeks of

treatment to assess the safety, tolerability, and usability of COSENTYX self-administration via the pre-

filled pen. Patients were randomised to COSENTYX received 150 mg or 300 mg doses at weeks 0, 1,

2, and 3, followed by the same dose every month starting at week 4. Patients were also randomised to

receive placebo at weeks 0, 1, 2, and 3, followed by the same dose every month starting at week 4.

SCULPTURE Study (A2304)

This trial evaluated 966 patients. All patients received COSENTYX 150 mg or 300 mg doses at weeks

0, 1, 2, 3, 4, 8 and 12 and then were randomised to receive either a maintenance regimen of the same

dose every month starting at Week 12 or a “retreatment as needed” regimen of the same dose.

Results

The 300 mg dose provided improved skin clearance across efficacy endpoints of PASI 75/90/100, and

IGA mod 2011 ‘clear’ or ‘almost clear’ responses across all studies with peak effects seen at week 16

Page 5 of 23

(see to Table 2 and Table 3). Therefore the 300 mg dose is recommended.

COSENTYX was efficacious in biologic-naive, biologic/anti-TNF-exposed and biologic/anti-TNF-failure

patients.

COSENTYX was associated with a fast onset of efficacy as shown in Figure 1 with a 50 % reduction in

mean PASI by week 3 for 300 mg.

Figure 1

Time course of percentage change from baseline of mean PASI score in ERASURE

trial (m = number of patients evaluable)

Page 6 of 23

Table 2

Summary of clinical response in ERASURE, FEATURE and JUNCTURE trials

Placebo

Week 12

Week 16

Week 52

150 mg

300 mg

150 mg

150 mg

300 mg

150 mg

ERASURE

Number of

patients

PASI 50

response n (%)

(8.9%)

(83.5%)

(90.6%)

(87.2%)

(91.4%)

187 (77%)

(84.5%)

PASI 75

response n (%)

(4.5%)

(71.6%)**

(81.6%)**

(77.4%)

(86.1%)

(60.1%)

(74.3%)

PASI 90

response n (%)

3 (1.2%)

(39.1%)**

(59.2%)**

(53.5%)

(69.8%)

88 (36.2%)

(60.0%)

PASI 100

response n (%)

2 (0.8%)

31 (12.8%)

70 (28.6%)

(21.0%)

(41.6%)

49 (20.2%)

96 (39.2%)

IGA mod 2011

“clear” or

“almost clear”

response n (%)

(2.40%)

(51.2%)**

(65.3%)**

(58.2%)

(73.5%)

(41.4%)

(60.4%)

FEATURE

Number of

patients

PASI 50

response n (%)

3 (5.1%)

51 (86.4%)

51 (87.9%)

PASI 75

response n (%)

0 (0.0%)

(69.5%)**

(75.9%)**

PASI 90

response n (%)

0 (0.0%)

27 (45.8%)

35 (60.3%)

PASI 100

response n (%)

0 (0.0%)

5 (8.5%)

25 (43.1%)

IGA mod 2011

“clear” or

“almost clear”

response n (%)

0 (0.0%)

(52.5%)**

(69.0%)**

JUNCTURE

Number of

patients

PASI 50

response n (%)

5 (8.2%)

48 (80.0%)

58 (96.7%)

PASI 75

response n (%)

2 (3.3%)

(71.7%)**

(86.7%)**

PASI 90

response n (%)

0 (0.0%)

24 (40.0%)

33 (55.0%)

PASI 100

response n (%)

0 (0.0%)

10 (16.7%)

16 (26.7%)

IGA mod 2011

“clear” or

“almost clear”

response n (%)

0 (0.0%)

(53.3%)**

(73.3%)**

*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 focusing on induration, erythema and scaling.

Treatment success of “clear” or “almost clear” consisted of no signs of psoriasis or normal to pink coloration of lesions, no

thickening of the plaque and none to minimal focal scaling.

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

Page 7 of 23

Table 3

Summary of clinical response in FIXTURE trial

Week 12

Week 16

Week 52

Placebo

150 mg

300 mg

Etanercept

150 mg

300 mg

Etanercept

150 mg

300 mg

Etanercept

Number

patients

PASI

response

n (%)

(15.1%)

(81.3%)

(91.6%)

(70.0%)

(88.7%)

(93.5%)

(79.6%)

(76.1%)

(84.8%)

(72.4%)

PASI

response

n (%)

(4.9%)

(67.0%)

(77.1%)

(44.0%)

(75.5%)

(86.7%)

(58.5%)

(65.7%)

(78.6%)

(55.4%)

PASI

response

n (%)

(1.5%)

(41.9%)

(54.2%)

(20.7%)

(53.8%)

(72.4%)

(31.3%)

(45.0%)

(65.0%)

(33.4%)

PASI 100

response

n (%)

(0%)

(14.4%)

(24.1%)

(4.3%)

(25.7%)

(36.8%)

(7.4%)

(19.9%)

(36.2%)

(9.9%)

2011

“clear”

“almost

clear”

response

n (%)

9 (2.8%)

(51.1%)

(62.5%)

(27.2%)

(61.2%)

(75.5%)

(39.3%)

(51.4%)

(67.8%)

(37.2%)

** p values versus etanercept: p=0.0250

An additional psoriasis study (CLEAR) evaluated 676 patients. Secukinumab 300 mg met the primary

and secondary endpoints by showing superiority to ustekinumab based on PASI 90 response at Week

16 and speed of onset of PASI 75 response at Week 4. 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 early and continued through Week 16.

Table 4

Summary of clinical response on CLEAR Study

Week 4

Week 16

Secukinumab 300 mg

Ustekinumab*

Secukinumab 300 mg

Ustekinumab*

Number of patients

PASI 75 response n (%)

167 (50.0%)**

69 (20.6%)

311 (93.1%)

277 (82.7%)

PASI 90 response n (%)

70 (21.0%)

18 (5.4%)

264 (79.0%)**

193 (57.6%)

PASI 100 response n

14 (4.2%)

3 (0.9%)

148 (44.3%)

95 (28.4%)

IGA mod 2011 “clear” or

“almost clear” response

n (%)

126 (37.7%)

41 (12.2%)

277 (82.9%)

226 (67.5%)

* Patients treated with secukinumab received 300 mg doses at Weeks 0, 1, 2 and 3, followed by the same dose at Weeks 4, 8

and 12. Patients treated with ustekinumab received 45 mg or 90 mg at Weeks 0 and 4 (dosed by weight as per approved posology)

** p values versus ustekinumab: p<0.0001

All plaque psoriasis phase III studies included approximately 15 to 25% of patients with concurrent

psoriatic arthritis at baseline. Improvements in PASI 75 in this patient population were similar to those

in the overall plaque psoriasis population.

In the subset of psoriatic arthritis patients in the ERASURE and FIXTURE studies, physical function

was assessed using the HAQ Disability Index (HAQ-DI). In these studies, patients treated with 150 mg

or 300 mg COSENTYX showed greater improvement from baseline in the HAQ-DI score (mean

decreases of -27.5% and -50.2% at week 12) compared to placebo (-8.9%). This improvement was

maintained up to week 52.

Patients in the SCULPTURE study that were randomised after week 12 to a “retreatment as needed”

maintenance regimen did not achieve adequate maintenance of response to either dose used. After 52

weeks of treatment patients with 300 mg “retreatment as needed” regimen achieved a PASI 75 of 41.0%

and a PASI 90 of 13.8%, whereas patients with a monthly maintenance regimen of 300 mg achieved a

PASI 75 of 78.2% and a PASI 90 of 59.7%. Similarly, patients with 150 mg “retreatment as needed”

regimen achieved a PASI 75 of 35.0% and a PASI 90 of 11.2%, whereas patients with a monthly

Page 8 of 23

maintenance regimen of 150 mg achieved a PASI 75 of 62.1% and a PASI 90 of 45.8% after 52 weeks

of treatment. Therefore a fixed monthly maintenance regimen is recommended.

Specific locations/forms of plaque psoriasis

additional

placebo-controlled

studies,

improvement

seen

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 nail

involvement. In the GESTURE study, secukinumab was superior to placebo at Week 16 (33.3% for 300

mg, 22.1% for 150 mg, and 1.5% for placebo) as assessed by significant improvement of the

Palmoplantar Investigator’s Global Assessment (ppIGA) 0 or 1 response (“clear” or “almost clear”) for

patients with moderate to severe palmoplantar plaque psoriasis.

Quality of Life / Patient reported outcomes

Statistically significant improvements at week 12 (Studies 1-4) from baseline compared to placebo were

demonstrated in the DLQI (Dermatology Life Quality Index), these improvements were maintained for

52 weeks (Studies 1 and 2).

Statistically significant improvements at week 12 from baseline compared to placebo (ERASURE and

FIXTURE Studies) in

patient reported signs and symptoms of itching, pain and scaling

were

demonstrated in the validated Psoriasis Symptom Diary.

Psoriatic Arthritis

The safety and efficacy of COSENTYX were assessed in 1,003 patients in two randomized, double-

blind, placebo-controlled phase III studies in patients with active psoriatic arthritis (>3 swollen and >3

tender

joints)

despite

non-steroidal

anti-inflammatory

drug

(NSAID),

corticosteroids

disease-

modifying anti-rheumatic drug (DMARD) therapy. Patients with each subtype of PsA were enrolled in

these studies, including polyarticular arthritis with no evidence of rheumatoid nodules, spondylitis with

peripheral arthritis, asymmetric peripheral arthritis, distal interphalangeal involvement and arthritis

mutilans. Patients in these studies had a diagnosis of PsA for a median of 3.9 to 5.3 years .

Approximately half of all enrolled patients had at least 3% BSA involvement with skin psoriasis at

baseline. Over 62% and 47% of the PsA patients had enthesitis and dactylitis at baseline, respectively.

In FUTURE 1 Study (PsA1 Study) and FUTURE 2 Study (PsA2 Study) 29% and 35% of patients,

respectively, were previously treated with an anti-TNFα agent and discontinued the anti-TNFα agent for

either lack of efficacy or intolerance (anti-TNFα-IR patients). For both studies, the primary endpoint

was American College of Rheumatology (ACR) 20 response at Week 24.

Key exclusion criteria across pivotal trials were: use of high potency opioid analgesics; ongoing use of

certain psoriasis treatments, e.g. topical or systemic corticosteroids or UV therapy; previous exposure

to secukinumab or any other biologic drugs for psoriasis and PsA except for those targeting TNFα,

patients with active, ongoing inflammatory disease other than PsA; patients with active, ongoing,

chronic or recurrent infectious disease; evidence of tuberculosis infection (enrolment was allowed for

patients with latent tuberculosis if appropriate treatment was initiated and maintained according to the

local treatment guideline); history of HIV, hepatitis B or hepatitis C; underlying immunocompromising

conditions; presence of lymphoproliferative disease, malignancy or history of malignancy within the past

5 years; significant medical problems including uncontrolled hypertension and congestive heart failure

(NYHA Class III and IV); patients with serum creatinine >132.6 micromol/L or with white blood cell count

<3,000 /microL,, platelets <100,000/microL, neutrophils <1,500/microL or haemoglobin <8.5 g/dL;

pregnant or nursing women; and women of child-bearing potential not using effective contraception

during the study.

Page 9 of 23

FUTURE 1 Study (F2306)

PsA1 Study evaluated 606 patients, of whom 60.7% had concomitant MTX. Patients randomized to

COSENTYX received 10 mg/kg, i.v. at Weeks 0, 2, and 4, followed by either 75 mg or 150 mg s.c. every

month starting at Week 8. Patients randomized to receive placebo who were non-responders at Week

16 (early rescue) and other placebo patients at Week 24 were crossed over to receive COSENTYX

(either 75 mg or 150 mg) at Week 16 followed by the same dose every month.

FUTURE 2 Study (F2312)

PsA2 Study evaluated 397 patients, of whom 46.6% had concomitant MTX. Patients randomized to

COSENTYX received 75 mg, 150 mg or 300 mg s.c. at Weeks 0, 1, 2, and 3, followed by the same

dose every month starting at Week 4. Patients randomized to receive placebo who were non-

responders at Week 16 (early rescue) were then crossed over to receive COSENTYX (either 150 mg

or 300 mg, s.c.) at Week 16 followed by the same dose every month. Patients randomized to receive

placebo who were responders at Week 16 were crossed over to receive COSENTYX (either 150 mg or

300 mg) at Week 24 followed by the same dose every month.

Signs and symptoms

In PsA2 Study, treatment with COSENTYX resulted in significant improvement in the measure of

disease activity compared to placebo at Weeks 16 and 24 (see Table 5).

Table 5

Clinical response in PsA 2 Study at Week 24

Placebo

Week 24

75 mg

150 mg

300 mg

Number of patients

randomized

ACR 20 response n (%)

(15.3%)

(29.3%*)

(51.0%***)

(54.0%***)

ACR 50 response n (%)

(7.1%)

(18.2%*)

(35.0%)

(35.0%***)

ACR 70 response n (%)

(1.0%)

(6.1%)

(21.0%**)

(20.0%**)

DAS28-CRP

-0.96

-1.12

-1.58***

-1.61***

Number of patients with

≥ 3% BSA psoriasis

skin involvement at

baseline

(43.9%)

(50.5%)

(58.0%)

(41.0%)

PASI 75 response n

(16.3%)

(28.0%)

(48.3%***)

(63.4%***)

PASI 90 response n

(9.3%)

(12.0%)

(32.8%**)

(48.8%***)

Dactylitis Resolution

n (%) †

(14.8%)

(30.3%)

(50.0%**)

(56.5%**)

Enthesitis Resolution

n (%) ‡

(21.5%)

(32.4%)

(42.2%*)

(48.2%**)

* p<0.05, ** p<0.01, *** p<0.00l; versus placebo

All p-values are adjusted for multiplicity of testing based on pre-defined hierarchy, except for ACR70, Dactylitis, and

Enthesitis, which were exploratory endpoints.

Non-responder imputation used for missing binary endpoint.

ACR: American College of Rheumatology; PASI: Psoriasis Area and Severity Index; DAS: Disease Activity Score; BSA:

Body Surface Area

† In patients with dactylitis at baseline (n=27, 33, 32, 46, respectively)

‡ In patients with enthesitis at baseline (n=65, 68, 64, 56, respectively)

The onset of action of COSENTYX occurred as early as Week 2. Statistically significant difference in

ACR 20 vs placebo was reached at Week 3. At Week 16, COSENTYX-treated patients demonstrated

significant improvements in signs and symptoms among which significantly higher responses in ACR 20

(33.3%, 60.0% and 57.0% for 75 mg, 150 mg and 300 mg, respectively) compared to placebo (18.4%).

The percentage of patients achieving ACR20 response by visit is shown in Figure 2.

Page 10 of 23

Figure 2

ACR 20 response in PsA 2 Study over time up to Week 24

Similar responses for primary and key secondary endpoints were seen in PsA patients regardless of

whether they were on concomitant MTX treatment or not.

Both, anti-TNFα-naïve and anti-TNFα–IR COSENTYX-treated patients, had a significantly higher ACR

20 response compared to placebo at Week 24, with a slightly higher response in the anti-TNFα- naïve

group (anti-TNFα-naïve: 37%, 64% and 58% for 75 mg, 150 mg and 300 mg, respectively, compared

to placebo 15.9%; anti-TNFα-IR: 15%, 30% and 46% for 75 mg, 150 mg and 300 mg, respectively,

compared to placebo 14.3%). Anti-TNFα–IR patients on 300mg showed higher response rates on

ACR20 compared to placebo patients (p<0.05) and demonstrated clinical meaningful benefit over 150

mg on multiple secondary endpoints. Improvements in the PASI75 response were seen in both

subgroups and the 300 mg dose showed statistically significant benefit in the anti-TNFα-IR patients.

Improvements were shown in all components of the ACR scores, including patient assessment of pain.

The proportion of patients achieving a modified PsA Response Criteria (PsARC) response was greater

in the COSENTYX-treated patients (38.4%, 62.0% and 63.0% for 75 mg, 150 mg and 300 mg,

respectively) compared to placebo (29.6%) at Week 24.

In PsA Study 1 and PsA Study 2, efficacy was maintained up to Week 52. In PsA Study 2, among 200

patients initially randomised to COSENTYX 150 mg and 300 mg, 178 (89%) patients were still on

treatment at Week 52. Of the 100 patients randomised to COSENTYX 150 mg, 64, 39 and 20 had an

ACR 20/50/70 response, respectively. Of the 100 patients randomised to COSENTYX 300 mg, 64, 44

and 24 had an ACR 20/50/70 response, respectively.

In PsA Study 1, inhibition of progression of structural damage was assessed radiographically and

expressed as the change in modified total Sharp Score (mTSS) and its components, the Erosion Score

(ES) and the Joint Space Narrowing score (JSN) at Weeks 24 and 52, compared to baseline. Week 24

data are presented in Table 6.

Percentage of responders

Time

(Weeks)

Page 11 of 23

Table 6

Change in modified Total Sharp Score in psoriatic arthritis

Placebo

N= 179

COSENTYX 75 mg

1

N= 181

COSENTYX 150 mg

1

N= 185

Total score

Baseline (SD)

28.4

(63.5)

20.4

(39.4)

22.3

(48.0)

Mean change at Week 24

0.57

0.02*

0.13*

* p<0.05 based on nominal, but not adjusted, p-value

10 mg/kg at Weeks 0, 2 and 4 followed s.c. doses of 75 mg or 150 mg

Inhibition of structural damage was maintained with COSENTYX treatment up to Week 52.

The percentage of patients with no-disease progression (defined as a change from baseline in modified

total Sharp score of ≤0.5) from randomization to Week 24 was 92.3% in secukinumab 10 mg/kg i.v.

load – 75 mg s.c. maintenance, 82.3% in secukinumab 10 mg/kg i.v. load – 150 mg s.c. maintenance

and 75.7% in placebo. The percentage of patients with no-disease progression, from Week 24 to Week

52, for the same above described regimen, was 85.8%, 85.7% and 86.8%, respectively.

Inhibition

progression

structural

damage

been

demonstrated

using

subcutaneous loading regimen approved for clinical use.

Physical function and health related quality of life

In PsA Study 2, patients treated with COSENTYX 150 mg and 300 mg showed improvement in physical

function compared to patients treated with placebo as assessed by Heath Assessment Questionnaire-

Disability Index (HAQ-DI) at Week 24 (and up to Week 52 in PsA Study 1). Improvements in HAQ-DI

scores were seen regardless of previous anti-TNFα exposure.

COSENTYX-treated patients reported significant improvements in health-related quality of life as

measured by the Short Form (36) Health Survey Physical Component Summary (SF-36 PCS) score

(p<0.001).

Ankylosing spondylitis

The safety and efficacy of COSENTYX were assessed in 590 patients in two randomised, double-blind,

placebo-controlled phase III studies in patients with active ankylosing spondylitis (AS) with a Bath

Ankylosing Spondylitis Disease Activity Index (BASDAI) ≥4 despite non-steroidal anti-inflammatory drug

(NSAID), corticosteroid or disease-modifying anti-rheumatic drug (DMARD) therapy. Patients in these

studies had a diagnosis of AS for a median of 2.7 to 5.8 years. For both studies, the primary endpoint

was at least a 20% improvement in Assessment of Spondyloarthritis International Society (ASAS 20)

criteria at Week 16.

In MEASURE 1 Study (AS1 Study) and MEASURE 2 Study (AS2 Study) 27.0% and 38.8% of patients,

respectively, were previously treated with an anti-TNFα agent and discontinued the anti-TNFα agent for

either lack of efficacy or intolerance (anti-TNFα-IR patients).

Key exclusion criteria across pivotal trials were: patients with total ankylosis of the spine; use of high

potency opioid analgesics; previous exposure to secukinumab or any other biologic drugs except for

those targeting TNFα, patients with active, ongoing inflammatory disease, other than AS; patients with

active, ongoing, chronic or recurrent infectious disease; evidence of tuberculosis infection (enrolment

was allowed for patients with latent tuberculosis if appropriate treatment was initiated and maintained

according to the local treatment guideline); history of HIV, hepatitis B or hepatitis C; underlying

immunocompromising conditions; presence of lymphoproliferative disease, malignancy or history of

malignancy within the past 5 years; significant medical problems including uncontrolled hypertension

and congestive heart failure (NYHA Class III and IV); patients with serum creatinine >132.6 micromol/L

or with white blood cell count <3,000 /microL, platelets <100,000/microL, neutrophils <1,500/microL or

haemoglobin <8.5 g/dL; pregnant or nursing women; and women of child-bearing potential not using

effective contraception during the study.

AS1 Study evaluated 371 patients, of whom 14.8% and 33.4% used concomitant MTX or sulfasalazine,

Page 12 of 23

respectively. Patients randomised to COSENTYX received 10 mg/kg, i.v. at Weeks 0, 2, and 4, followed

by either 75 mg or 150 mg s.c. every month starting at week 8. Patients randomised to placebo who

were non-responders at Week 16 (early rescue) and all other placebo patients at Week 24 were crossed

over to receive COSENTYX (either 75 mg or 150 mg s.c.), followed by the same dose every month.

AS2 Study evaluated 219 patients, of whom 11.9% and 14.2% used concomitant MTX or sulfasalazine,

respectively. Patients randomised to COSENTYX received 75 mg or 150 mg s.c. at Weeks 0, 1, 2, and

3, followed by the same dose every month starting at Week 4. At Week 16, patients who were

randomised to placebo at baseline were re-randomised to receive COSENTYX (either 75 mg or 150

mg) s.c. every month.

Signs and symptoms

In AS2 Study, treatment with COSENTYX 150 mg resulted in greater improvement in measures of

disease activity compared with placebo at Week 16 (see Table 7).

Table 7

Clinical response in AS2 Study at Week 16

Outcome (p-value vs placebo)

Placebo

(n = 74)

75 mg

(n = 73)

150 mg

(n = 72)

Efficacy at Week 16

ASAS20 response, %

28.4

41.1

61.1***

ASAS40 response, %

10.8

26.0

36.1***

hsCRP, (post-BSL/BSL ratio)

1.13

0.61

0.55***

ASAS5/6, %

34.2

43.1***

ASAS partial remission, %

15.1

13.9

BASDAI50, %

10.8

24.7*

30.6**

ASDAS-CRP major improvement

15.1*

25.0***

*p<0.05; **p<0.01; ***p< 0.001 vs. placebo

All p-values adjusted for multiplicity of testing based on pre-defined hierarchy, except BASDAI50 and ASDAS-CRP

Non-responder imputation used for missing binary endpoint

ASAS: Assessment of SpondyloArthritis International Society Criteria; BASDAI: Bath Ankylosing Spondylitis Disease Activity

Index; hsCRP: high-sensitivity C-reactive protein; ASDAS: Ankylosing Spondylitis Disease Activity Score; BSL: baseline; LS:

least square

The onset of action of COSENTYX 150 mg occurred as early as Week 1 for ASAS20 and Week 2 for

ASAS40 (superior to placebo) in AS2 Study.

Page 13 of 23

Figure 3

ASAS20 responses in AS 2 Study over time up to Week 16

ASAS20 responses were improved at Week 16 in both antiTNFα-naïve patients (68.2% vs. 31.1%;

p<0.05) and anti-TNFα-IR patients (50.0% vs. 24.1%; p<0.05) for COSENTYX 150 mg compared with

placebo, respectively.

In both AS studies, COSENTYX -treated patients (150 mg in AS2 Study and both regimens in AS1

Study) demonstrated significantly improved signs and symptoms at Week 16, with comparable

magnitude of response and efficacy was maintained up to Week 52 in both anti-TNFα-naive and anti-

TNFα-IR patients. In AS Study 2, among 72 patients initially randomised to COSENTYX 150 mg, 61

(84.7%) patients were still on treatment at Week 52. Of the 72 patients randomised to COSENTYX 150

mg, 45 and 35 had an ASAS 20/40 response, respectively.

Spinal mobility

Patients treated with COSENTYX 150 mg showed improvements in spinal mobility as measured by

change from baseline in BASMI at Week 16 for both AS Study 1 (-0.40 versus -0.12 for placebo;

p=0.0114) and AS Study 2 (-0.51 versus -0.22 for placebo; p=0.0533). These improvements were

sustained up to Week 52.

Physical function and health-related quality of life

In AS Study 1 and 2, patients treated with COSENTYX 150 mg showed improvements in health-related

quality of life as measured by ASQoL p = 0.001) and SF-36 PCS (p< 0.001). These improvements were

sustained up to Week 52.

Patients treated with COSENTYX 150 mg also showed improvements on exploratory endpoints in

physical function as assessed by the Bath Ankylosing Spondylitis Functional Index (BASFI) compared

to placebo (-2.15 versus -0.68)..

INDICATION

Plaque psoriasis

COSENTYX is indicated for the treatment of moderate to severe plaque psoriasis in adult patients who

are candidates for systemic therapy or phototherapy.

Psoriatic arthritis

COSENTYX is indicated for the treatment of adult patients with active psoriatic arthritis when the

response to previous disease-modifying anti-rheumatic drug (DMARD) therapy has been inadequate.

Time

(Weeks)

Percentage of responders

Page 14 of 23

Ankylosing spondylitis

COSENTYX is indicated for the treatment of adult patients with active ankylosing spondylitis.

CONTRAINDICATIONS

Severe hypersensitivity reactions to the active substance or to any of the excipients (see ingredients in

DESCRIPTION, and ADVERSE EFFECTS).

Clinically important, active infections (see PRECAUTIONS).

PRECAUTIONS

Infections

COSENTYX has the potential to increase the risk of infections. In clinical studies, infections have been

observed in patients receiving COSENTYX (see ADVERSE EFFECTS). Most of these were mild or

moderate.

Related to the mechanism of action of COSENTYX, non-serious mucocutaneous candida infections

were more frequently reported for secukinumab than placebo in the psoriasis clinical studies (3.55 per

100 patient years for secukinumab 300 mg versus 1.00 per 100 patient years for placebo) (see Adverse

Effects ).

A similar increase in risk of infection was seen in placebo-controlled trials in patients with psoriatic

arthritis and ankylosing spondylitis. The incidence of some types of infections appeared to be dose-

dependent in clinical studies (see Adverse Effects).

Caution should be exercised when considering the use of COSENTYX in patients with a chronic

infection or a history of recurrent infection.

Patients should be instructed to seek medical advice if signs or symptoms suggestive of an infection

occur. If a patient develops a serious infection, the patient should be closely monitored and COSENTYX

should not be administered until the infection resolves.

No increased susceptibility to tuberculosis was reported from clinical studies. However, COSENTYX

should not be given to patients with active tuberculosis. Anti-tuberculosis therapy should be considered

prior to initiation of COSENTYX in patients with latent tuberculosis.

Crohn’s disease

Caution should be exercised, when prescribing COSENTYX to patients with inflammatory bowel

disease. Exacerbations, in some cases serious, occurred in COSENTYX treated patients during clinical

trials in plaque psoriasis, psoriatic arthritis, and ankylosing spondylitis. In addition, new onset

inflammatory bowel disease cases occurred in clinical trials with COSENTYX.

Patients who are treated with COSENTYX should be monitored for signs and symptoms of inflammatory

bowel disease.

Hypersensitivity reactions

In clinical studies, rare cases of anaphylactic reactions have been observed in patients receiving

COSENTYX. If an anaphylactic or other serious allergic reaction occurs, administration of COSENTYX

should be discontinued immediately and appropriate therapy initiated.

Latex-sensitive individuals – prefilled-syringe/pen only

The removable cap of the COSENTYX pre-filled syringe/pen contains a derivative of natural rubber

latex. Although no natural rubber latex is detected in the cap, the safe use of COSENTYX pre-filled

syringe/pen in latex-sensitive individuals has not been studied.

Page 15 of 23

Vaccinations

Live vaccines should not be given concurrently with COSENTYX (see INTERACTIONS WITH OTHER

MEDICINES).

Patients treated with COSENTYX may receive vaccinations, except for live vaccines. In a study, after

meningococcal and inactivated influenza vaccinations, a similar proportion of COSENTYX-treated and

placebo-treated patients were able to mount an adequate immune response of at least a 4-fold increase

in antibody titres to meningococcal or influenza vaccines. The data suggest that COSENTYX does not

suppress the humoral immune response to the meningococcal and influenza vaccines.

Patients receiving COSENTYX may receive concurrent inactivated or non-live vaccinations.

Use in Patients with Hepatic or Renal Impairment

No data are available in patients with hepatic or renal impairment.

Fertility

The effect of COSENTYX on human fertility has not been evaluated.

Animal studies do not indicate direct or indirect harmful effects with respect to fertility.

Fertility was unaffected in mice treated with an anti-murine IL17-A antibody.

Women of child-bearing potential

There are no special recommendations for women of child-bearing potential.

Use in Pregnancy (Category C)

There are no adequate data from the use of COSENTYX in pregnant women. Secukinumab was shown

to cross the placenta in monkeys. Use of secukinumab during pregnancy may compromise the immunity

of the fetus and neonate.

In an embryofetal development study in cynomolgus monkeys, secukinumab showed no maternal

toxicity, embryofetal toxicity or teratogenicity when administered throughout organogenesis and late

gestation at up to 150mg/kg/week.

COSENTYX should be used in pregnancy only if the benefits clearly outweigh the potential risks.

If secukinumab has been used during pregnancy, administration of live vaccines to newborns/ infants

for 16 weeks after the mother’s last dose of secukinumab is generally not recommended.

Use in Lactation

It is not known whether secukinumab is excreted in human milk. Because immunoglobulins are excreted

in human milk, caution should be exercised when COSENTYX is administered to a woman who is

breast-feeding and a decision on whether to discontinue breast-feeding during treatment should be

made.

Paediatric Use

Safety and effectiveness in patients below the age of 18 years have not yet been established.

Use in the Elderly

Based on population PK analysis, clearance in patients aged 65 and older (n=230) and patients less

than 65 years of age was similar.

Carcinogenicity

Secukinumab has not been evaluated for carcinogenic potential.

Page 16 of 23

Genotoxicity

COSENTYX has not been evaluated for genotoxic potential.

Effect on laboratory tests

There is no known interference between COSENTYX and routine laboratory tests.

Effects on ability to drive and use machines

No studies on the effects on the ability to drive and use of machines have been performed.

INTERACTIONS WITH OTHER MEDICINES

Live vaccines should not be given concurrently with COSENTYX (see also PRECAUTIONS).

No interaction studies have been performed in humans. There is no direct evidence for the role of IL-l

7 A in the expression of CYP450 enzymes. The formation of some CYP450 enzymes is suppressed by

increased levels of cytokines during chronic inflammation. Thus, anti-inflammatory treatments, such as

with the IL-17 A inhibitor secukinumab, may result in normalisation of CYP450 levels with accompanying

lower exposure of CYP450-metabolised co-medications. Therefore, a clinically relevant effect on

CYP450 substrates with a narrow therapeutic index, where the dose is individually adjusted (e.g.

warfarin) cannot be excluded. On initiation of secukinumab therapy in patients being treated with these

types of medicinal products, therapeutic monitoring should be considered.

No interaction was seen when COSENTYX was administered concomitantly with methotrexate (MTX)

and/or corticosteroids in arthritis studies (including in patients with psoriatic arthritis and ankylosing

spondylitis).

ADVERSE EFFECTS

Summary of the safety profile

A total of 6,200 patients have been treated with COSENTYX in blinded and open-label clinical studies

in various indications (plaque psoriasis and other autoimmune conditions), representing 4,649 patient

years of exposure. Of these, 3,671 patients were exposed to COSENTYX for at least one year,

representing 6,267 patient years of exposure.

Adverse reactions in plaque psoriasis

Four placebo-controlled phase III studies in plaque psoriasis were pooled to evaluate the safety of

COSENTYX in comparison to placebo up to 12 weeks after treatment initiation. In total, 2,076 patients

were evaluated (692 patients on 150 mg, 690 patients on 300 mg and 694 patients on placebo).

The most frequently reported adverse drug reactions (ADRs) were upper respiratory tract infections

(most frequently nasopharyngitis, rhinitis). Most of the events were mild or moderate in severity.

In the placebo-controlled period of plaque psoriasis phase III studies the proportion of patients who

discontinued treatment due to adverse events was approximately 1.2 % in the COSENTYX arm and

1.2 % in the placebo arm.

The adverse reactions from clinical studies (Table 8 and Table 9) are listed by MedDRA system organ

class. Within each system organ class, the ADRs are ranked by frequency. Within each frequency

grouping, adverse drug reactions are presented in order of decreasing seriousness. In addition, the

corresponding frequency category for each adverse drug reaction is based on the following convention:

very common (> 1/10); common (> 1/100, ≤ 1/10); uncommon (> 1/1,000, ≤ 1/100); rare (≥ 1/10,000, ≤

1/1,000) very rare (< 1/10,000).

Page 17 of 23

Table 8

Adverse Drug Reactions reported by ≥ 1 % of psoriasis patients through Week 12

in Phase III ERASURE, FIXTURE, FEATURE and JUNCTURE studies

Adverse Reactions

COSENTYX

Placebo

(N=694) n (%)

Frequency

category

300 mg

(N=690) n (%)

150 mg

(N=692) n (%)

Infections and infestations

Nasopharyngitis

79 (11.4)

85 (12.3)

60 (8.6)

Very

common

Upper respiratory tract infection

17 (2.5)

22 (3.2)

5 (0.7)

Common

Rhinitis

10 (1.4)

10 (1.4)

5 (0.7)

Common

Oral herpes

9 (1.3)

1 (0.1)

2 (0.3)

Common

Pharyngitis

8 (1.2)

7 (1.0)

0 (0)

Common

Gastrointestinal disorders

Diarrhoea

28 (4.1)

18 (2.6)

10 (1.4)

Common

Skin and subcutaneous tissue disorders

Urticaria

4 (0.6)

8 (1.2)

1 (0.1)

Common

Respiratory, thoracic and mediastinal disorders

Rhinorrhoea

8 (1.2)

2 (0.3)

1 (0.1)

Common

ADR frequencies are based upon the highest percentage rate seen in any of the secukinumab groups

Table 9

Adverse Drug Reactions reported by ≥ 1 % of psoriasis patients through Week 12

in Phase III FIXTURE Study (A2303)

Adverse Reactions

COSENTYX

Placebo

N=327

n (%)

Etanercept

N=323

n (%)

Frequency

category

300 mg

N=326

n (%)

150 mg

N=327

n (%)

Infections and infestations

Nasopharyngitis

35 (10.7)

45 (13.8)

26 (8.0)

36 (11.1)

Very

common

Upper

Respiratory

Tract

Infection

7 (2.1)

10 (3.1)

3 (0.9)

7 (2.2)

Common

Rhinitis

7 (2.1)

4 (1.2)

4 (1.2)

3 (0.9)

Common

Oral Herpes

5 ( 1.5)

1 ( 0.3)

0 ( 0.0)

0 ( 0.0)

Common

Pharyngitis

4 ( 1.2)

5 ( 1.5)

0 ( 0.0)

0 ( 0.0)

Common

Gastrointestinal disorders

Diarrhoea

17 (5.2)

12 (3.7)

6 (1.8)

11 (3.4)

Common

Skin and subcutaneous tissue

disorders

Urticaria

1 ( 0.3)

5 ( 1.5)

0 ( 0.0)

2 ( 0.6)

Common

Respiratory,

thoracic

mediastinal disorders

Rhinorrhoea

7 (2.1)

1 (0.3)

1 (0.3)

2 (0.6)

Common

ADR frequencies are based upon the highest percentage rate seen in any of the secukinumab groups

Adverse reactions that occurred at less than 1 % frequency in the placebo-controlled period of the

ERASURE, FIXTURE, FEATURE and JUNCTURE studies through week 12 are given in Table 10.

Table 10

Adverse effects reported at < 1 % frequency through Week 12 in psoriasis clinical

trial patients

Infections and infestations

Uncommon:

Sinusitis, tinea pedis, tonsillitis, oral candidiasis, otitis externa

Eye disorders

Uncommon:

Conjunctivitis

Blood and lymphatic system disorders

Uncommon:

Neutropenia

Page 18 of 23

Adverse drug reactions from spontaneous reports and literature cases (frequency not

known)

The following adverse drug reactions have been derived from post-marketing experience with Cosentyx

via spontaneous case reports and literature cases. Because these reactions are reported voluntarily

from a population of uncertain size, it is not possible to reliably estimate their frequency which is

therefore categorized as not known. Adverse drug reactions are listed according to system organ

classes in MedDRA. Within each system organ class, ADRs are presented in order of decreasing

seriousness.

Table 11

Adverse drug reactions from spontaneous reports and literature (frequency not

known)

Infections and infestations

Mucosal and cutaneous candidiasis

Infections

In the placebo-controlled period of clinical studies in plaque psoriasis (a total of 1,382 patients treated

with COSENTYX and 694 patients treated with placebo for up to 12 weeks), infections were reported

in 28.7 % of patients treated with COSENTYX compared with 18.9 % of patients treated with placebo.

Most of these were mild or moderate. Serious infections occurred in 0.14 % of patients treated with

COSENTYX and in 0.3 % of patients treated with placebo (see PRECAUTIONS).

Over the entire treatment period (a total of 3,430 patients treated with COSENTYX for up to 52 weeks

for the majority of patients), infections were reported in 47.5 % of patients treated with COSENTYX (0.9

per patient-year of follow-up). Serious infections were reported in 1.2 % of patients treated with

COSENTYX (0.015 per patient-year of follow-up).

There was an increase in mucosal or cutaneous candidiasis, related to the mechanism of action. The

cases were mild or moderate in severity, non-serious, responsive to standard treatment and did not

necessitate treatment discontinuation. Frequency of candida infection was 1.2% (secukinumab 300

mg) vs 0.3% (placebo and etanercept arms) in the induction period.

Infection rates as observed in psoriatic arthritis and ankylosing spondylitis clinical studies were similar

to what was observed in the psoriasis studies.

Neutropenia

In psoriasis phase 3 clinical studies, neutropenia was more frequently observed with secukinumab than

with placebo, but most cases were mild, transient and reversible. Neutropenia <l.0-0.5 x l0

/L (CTCAE

Grade 3) was reported in 18 out of 3,430 (0.5%) patients on secukinumab, with no dose dependence

and no temporal relationship to infections in 15 out of 18 cases. There were no reported cases of more

severe neutropenia. Non-serious infections with usual response to standard care and not requiring

discontinuation of COSENTYX were reported in the remaining 3 cases.

The frequency of neutropenia in psoriatic arthritis and ankylosing spondylitis is similar to psoriasis.

Rare cases of neutropenia <0.5x 10

/L (CTCAE Grade 4) were reported.

Hypersensitivity reactions

In clinical studies, urticaria and rare case of anaphylactic reaction to COSENTYX were observed.

Immunogenicity

In psoriasis, psoriatic arthritis and ankylosing spondylitis clinical studies less than 1% of patients treated

with COSENTYX developed antibodies to secukinumab up to 52 weeks of treatment. About half of the

treatment emergent anti-drug antibodies were neutralising, but this was not associated with loss of

efficacy or PK abnormalities.

Reproductive system related adverse events

In the induction period of clinical studies, mild and moderate reproductive system adverse events were

reported

females,

including:

dysmenorrhoea

(secukinumab

1.9%;

placebo,

0.5%;

etanercept, 1.1%), menorrhagia (secukinumab 300 mg, 0.9%; placebo, 0%; etanercept, 0%) and

Page 19 of 23

metrorrhagia (including menometrorrhagia) (secukinumab 300 mg, 1.4%; placebo, 0%; etanercept,

0%). Women of child-bearing potential were included in studies only if using adequate contraception.

Major adverse cardiovascular events (MACE)

In the secukinumab clinical trials, MACE events were observed in patients receiving secukinumab. In

the Phase 3 studies in psoriasis, PsA and AS, the exposure adjusted incidence rates of adjudication-

confirmed MACE cases per 100 patient-years was 0.49 (19/3911.6 patient-years, 95% CI 0.29, 0.76)

for secukinumab versus 0.00 (0/351.3 patient-years, 95% CI 0.00, 1.05) for placebo. In the overall

secukinumab program, the exposure adjusted incidence rates of adjudication-confirmed cases per 100

patient-years for secukinumab was 0.40 (25/6259.8 patient-years, 95% CI 0.26, 0.59) versus 0.39

(2/515.1 patient-years, 95% CI 0.05, 1.40) for placebo.

Adverse reactions in psoriatic arthritis

COSENTYX was studied in two placebo-controlled psoriatic arthritis trials with 1,003 patients (703

patients on COSENTYX and 300 patients on placebo) for a total exposure of 1,061 patient- years of

study exposure (median duration of exposure for secukinumab-treated patients: 456 days in PsA1

Study and 245 days in PsA2 Study). The adverse events that occurred at a proportion of at least 2%

and at a higher proportion in the COSENTYX groups than the placebo groups during the 16-week

placebo-controlled period were nasopharyngitis, upper respiratory tract infection, headache, nausea,

and hypercholesterolemia. The safety profile observed in patients with psoriatic arthritis treated with

COSENTYX is consistent with the safety profile in psoriasis.

Similar to the clinical trials in patients with psoriasis, there was an increased proportion of patients with

infections in the COSENTYX groups (29%) compared to placebo group (26%) (see PRECAUTIONS).

There were cases of Crohn’s disease and ulcerative colitis that include patients who experienced either

exacerbations or the development of new disease. There were three cases of inflammatory bowel

disease, of which two patients received secukinumab and one received placebo (see PRECAUTIONS).

Cholesterol and triglycerides

CTCAE Grade 1 and Grade 2 elevations of blood cholesterol and triglyceride levels were reported in

patients receiving secukinumab compared to placebo in psoriatic arthritis clinical trials.

The elevations of cholesterol levels were limited primarily to CTCAE Grade 1 (29.6% vs. 22.7%,

respectively) and Grade 2 (1.6% vs. 0.3%, respectively). No cases of CTCAE Grade 3 and Grade 4

cholesterol levels were observed in either secukinumab or placebo groups during the placebo controlled

period.

An increase in blood triglycerides levels was also observed in psoriatic arthritic patients receiving

secukinumab compared to placebo (CTCAE Grade 1: 28.3% vs. 20.8%, Grade 2: 4.7% vs. 3.9%, Grade

3: 0.7% vs. 0.7% and Grade 4: 0.4% vs. 0.0%, respectively) up to Week 16.

Elevations (mainly CTCAE Grade 1 and Grade 2) in cholesterol and triglycerides were also observed

during long-term treatment with secukinumab.

Hepatic transaminases

During the placebo-controlled period, increased incidence of elevated hepatic transaminases was

observed in psoriatic arthritis patients treated with secukinumab compared to placebo. The elevations

in hepatic transaminases were seen primarily in CTCAE Grade 1 (ALT: 18.6% vs 15.8%; AST: 13.0%

vs. 12.4%, respectively). No difference in the incidence of elevated ALT and AST was seen between

secukinumab and placebo in CTCAE Grade 2 and Grade 3. No cases of CTCAE Grade 4 were

observed.

Elevations (mainly CTCAE Grade 1 and Grade 2) in ALT and AST was also observed during the long-

term treatment with secukinumab.

Page 20 of 23

Adverse reactions in ankylosing spondylitis

COSENTYX was studied in two placebo-controlled ankylosing spondylitis trials with 590 patients (394

patients on COSENTYX and 196 patients on placebo) for a total of 755 patient-years of study exposure

(median duration of exposure for secukinumab-treated patients: 469 days in AS 1 Study and 460 days

in AS 2 Study). During the 16-week placebo-controlled period of the trials in patients with ankylosing

spondylitis, the overall proportion of patients with adverse events was higher in the secukinumab groups

than the placebo-treatment groups (66% and 59%, respectively). The adverse events that occurred at

a proportion of at least 2% and at a higher proportion in the COSENTYX groups than the placebo groups

during the 16-week placebo-controlled period were nasopharyngitis, nausea, and upper respiratory tract

infection. The safety profile observed in patients with ankylosing spondylitis treated with COSENTYX is

consistent with the safety profile in psoriasis.

Similar to clinical trials in patients with psoriasis, there was an increased proportion of patients with

infections

COSENTYX

groups

(31%)

compared

placebo

group

(18%)

(see

PRECAUTIONS).

In the ankylosing spondylitis program, with 571 patients exposed to COSENTYX there were 8 cases of

inflammatory bowel disease during the entire treatment period (5 Crohn’s (0.7 per 100 patient-years)

and 3 ulcerative colitis (0.4 per 100 patient-years)). During the placebo-controlled 16-week period, there

were 2 Crohn’s disease exacerbations and 1 new onset ulcerative colitis case that was a serious

adverse event in patients treated with COSENTYX compared to none of the patients treated with

placebo. During the remainder of the study when all patients received COSENTYX, 1 patient developed

Crohn’s disease, 2 patients had Crohn’s exacerbations, 1 patient developed ulcerative colitis, and 1

patient had an ulcerative colitis exacerbation (see PRECAUTIONS).

Cholesterol and triglycerides

CTCAE Grade 1 and Grade 2 elevations of blood cholesterol and triglyceride levels were reported in

patients receiving secukinumab compared to placebo in ankylosing spondylitis clinical trials.

The elevations of cholesterol levels were limited primarily to CTCAE Grade 1 (20.0% vs. 19.8%,

respectively) . Increase in CTCAE Grade 2 cholesterol levels was uncommon (0.8% vs. 0.0%,

respectively) and no cases of CTCAE Grade 3 and Grade 4 cholesterol levels were observed in both

secukinumab and placebo groups during the placebo controlled period.

An increase in blood triglycerides levels was also observed in ankylosing pondylitis patients receiving

secukinumab or placebo (CTCAE Grade 1: 17.8% vs. 17.1%, Grade 2: 2.7% vs. 2.7%, and Grade 3:

0.8% vs. 0.5%, respectively). No cases of CTCAE Grade 4 triglyceride levels were reported during the

placebo-controlled period.

Elevations (mainly CTCAE Grade 1 and Grade 2) in cholesterol and triglycerides were also observed

during long-term treatment with secukinumab.

Hepatic transaminases

During the placebo-controlled period, increased incidence of elevated hepatic transaminases was

observed in ankylosing spondylitis patients treated with secukinumab compared to placebo. The

elevations in hepatic transaminases were seen primarily in CTCAE Grade 1 (ALT: 16.6% vs 7.1%; AST:

11.3% vs. 7.0%, respectively) . Increase in CTCAE Grade 2 and Grade 3 hepatic transaminase levels

was uncommon in both secukinumab and placebo groups (Grade 2 ALT: 1.0% vs. 0.5%, AST: 0.5%

vs. 0.0%; Grade 3 ALT: 0.8% vs. 0.0%, AST: 0.8% vs.1.6%, respectively). One case of CTCAE Grade

4 ALT levels was reported in the placebo group and no cases of CTCAE Grade 4 ALT and AST levels

were reported in the secukinumab group.

Elevations (mainly CTCAE Grade 1 and Grade 2) in ALT and AST was also observed during the long-

term treatment with secukinumab.

Page 21 of 23

DOSAGE AND ADMINISTRATION

Dosage

Plaque psoriasis

The recommended dose is 300 mg by subcutaneous injection with initial dosing at weeks 0, 1, 2, and

3, followed by monthly maintenance dosing of 300 mg starting at week 4. Each 300 mg dose is given

as two subcutaneous injections of 150 mg.

Psoriatic arthritis

The recommended dose is 150 mg by subcutaneous injection with initial dosing at Weeks 0, 1, 2 and

3, followed by monthly maintenance dosing starting at Week 4.

For patients who are anti-TNFα inadequate responders (IR) or patients with concomitant moderate to

severe plaque psoriasis, the recommended dose is 300 mg by subcutaneous injection with initial dosing

at Weeks 0, 1, 2 and 3, followed by monthly maintenance dosing starting at Week 4. Each 300 mg dose

is given as two subcutaneous injections of 150 mg.

COSENTYX may be administered with or without methotrexate.

Ankylosing spondylitis

The recommended dose is 150 mg by subcutaneous injection with initial dosing at Weeks 0, 1, 2 and

3, followed by monthly maintenance dosing starting at Week 4.

Assessment Prior to Initiation of COSENTYX

Evaluate patients for tuberculosis (TB) infection prior to initiating treatment with COSENTYX (see

PRECAUTIONS)

Special populations

Patients with renal or hepatic impairment

COSENTYX has not been specifically studied in these patient populations. No dose recommendations

can be made.

Paediatric and adolescent patients

Safety and effectiveness in patients below the age of 18 years have not yet been established.

Elderly patients (≥ 65 years of age)

No dose adjustment is needed for elderly patients.

Administration

The product is for single use in one patient only. Discard any residue.

Powder for injection

COSENTYX is administered by subcutaneous injection. Each vial of COSENTYX must be reconstituted

with 1 mL of sterile water for injections to obtain a 150 mg/mL solution. The powder for injection should

be administered by healthcare professionals only.

Prefilled syringe and pre-filled pen

COSENTYX is administered by subcutaneous injection. If possible, areas of the skin that show psoriasis

should be avoided as injection sites.

Before injection, secukinumab may be allowed to reach room temperature (20 minutes) without

removing the needle cap during this time.

Prior to administration, the liquid must be checked whether it is clear and colourless. The solution should

not be used if discoloured, or cloudy, or if foreign particles are present.

After proper training in subcutaneous injection technique, patients or appropriate care giver may self-

Page 22 of 23

inject COSENTYX if a physician determines that it is appropriate. However, the physician should ensure

appropriate follow-up of patients. Patients should be instructed to inject the full amount of COSENTYX

according

instructions

provided

package

leaflet.

Comprehensive

instructions

administration are given in the package leaflet.

OVERDOSAGE

No case of overdose has been reported in clinical studies.

Doses up to 30 mg/kg (i.e. approximately 2,000 mg to 3,000 mg) have been administered intravenously

in clinical studies without dose-limiting toxicity.

In the event of overdose, it is recommended that the patient be monitored for any signs or symptoms

of adverse reactions and appropriate symptomatic treatment be instituted immediately.

Contact the Poisons Information Centre on 13 11 26 for advice on management of an overdose.

PRESENTATION AND STORAGE CONDITIONS

Presentations

Powder for Solution:

secukinumab 150 mg as a sterile white solid lyophilisate for subcutaneous

injection. Packs containing 1* or 2* single-use vials.

Prefilled syringe:

secukinumab 150 mg/1 mL solution for subcutaneous injection in a single

use pre-filled syringe (PFS). The sterile solution is colourless to slightly

yellow. Packs containing 1* or 2* pre-filled syringes.

Prefilled pen:

secukinumab 150 mg/1 mL solution for subcutaneous injection in a single

use pre-filled pen. The sterile solution is colourless to slightly yellow. The

pen consists of a PFS assembled into a pen with a removable rubber cap.

Packs containing 1* or 2* pre-filled pens.

*Not all pack sizes or presentations may be marketed.

Storage

Powder for Solution:

Store at 2-8°C. Store in the original package

Prefilled syringe:

Store at 2-8°C. Do not freeze. Protect from light.

Store in the original package.

Prefilled pen:

Store at 2-8°C. Do not freeze. Protect from light.

Store in the original package.

NAME AND ADDRESS OF THE SPONSOR

Novartis Pharmaceuticals Australia Pty Limited

ABN 18 004 244 160

54 Waterloo Road

Macquarie Park NSW 2113

= Registered Trademark

POISON SCHEDULE OF THE MEDICINE

Schedule 4 - Prescription medicine

DATE OF FIRST INCLUSION IN THE AUSTRALIAN REGISTER OF THERAPEUTIC

GOODS

12 January 2015:

COSENTYX powder for solution*

12 January 2015:

COSENTYX prefilled syringe

12 January 2015:

COSENTYX prefilled pen

Page 23 of 23

DATE OF MOST RECENT AMENDMENT

23 May 2017

__________________________________________________________________________

Internal document code

cos230517i based on CDS dated 17 March 2017

24-9-2018

Cosentyx (Novartis Europharm Limited)

Cosentyx (Novartis Europharm Limited)

Cosentyx (Active substance: secukinumab) - PSUSA - Modification - Commission Decision (2018)6213 of Mon, 24 Sep 2018 European Medicines Agency (EMA) procedure number: EMEA/H/C/PSUSA/00010341/201712

Europe -DG Health and Food Safety