Summary Basis of Decision for Cosentyx

Review decision

The Summary Basis of Decision explains why the product was approved for sale in Canada. The document includes regulatory, safety, effectiveness and quality (in terms of chemistry and manufacturing) considerations.


Product type:

Drug

Summary Basis of Decision (SBD) documents provide information related to the original authorization of a product. The SBD for Cosentyx is located below.

Recent Activity for Cosentyx

SBDs written for eligible drugs approved after September 1, 2012 will be updated to include post-authorization information. This information will be compiled in a Post-Authorization Activity Table (PAAT). The PAAT will include brief summaries of activities such as submissions for new uses of the product, and whether Health Canada's decisions were negative or positive. PAATs will be updated regularly with post-authorization activity throughout the product's life cycle.

Post-Authorization Activity Table (PAAT) for Cosentyx

Updated:

2023-02-21

The following table describes post-authorization activity for Cosentyx, a product which contains the medicinal ingredient secukinumab. For more information on the type of information found in PAATs, please refer to the Frequently Asked Questions: Summary Basis of Decision (SBD) Project: Phase II and to the list of abbreviations that are found in PAATs.

For additional information about the drug submission process, refer to the Management of Drug Submissions and Applications Guidance.

Drug Identification Numbers (DINs):

  • DIN 02438062 – 150 mg/mL, secukinumab, powder for solution, subcutaneous administration
  • DIN 02438070 – 150 mg/mL, secukinumab, solution, subcutaneous administration (pre-filled syringe/pre-filled pen)
  • DIN 02525569 – 75 mg/0.5 mL, secukinumab, solution, subcutaneous administration (pre-filled syringe)
  • DIN 02529653 – 300 mg/2 mL, secukinumab, solution, subcutaneous administration (pre-filled syringe)
  • DIN 02529661 – 300 mg/2 mL, secukinumab, solution, subcutaneous administration (pre-filled pen)

Post-Authorization Activity Table (PAAT)

Activity/submission type, control number Date submitted Decision and date Summary of activities
NC # 268180 2022-09-27 Issued NOL 2023-01-09 Submission filed as a Level II (90 day) Notifiable Change (Moderate Quality Changes) to change the drug product batch size, add a testing site for the drug product, and change the specifications used to release the drug product. The submission was reviewed and considered acceptable, and an NOL was issued.
SNDS # 257230 2021-10-04 Issued NOC 2022-09-20 Submission filed as a Level I – Supplement for a new indication. The indication authorized was: the treatment of active enthesitis-related arthritis (ERA) and active juvenile psoriatic arthritis (JPsA) in patients 6 years and older whose disease has responded inadequately to, or who cannot tolerate, conventional therapy. The submission was reviewed and considered acceptable, and an NOC was issued. A Regulatory Decision Summary was published.
SNDS # 255983 2021-08-23 Issued NOC 2022-08-10 Submission filed as a Level I – Supplement for two new dosage forms, with no change to the previously-approved indications. The submission was reviewed and considered acceptable, and an NOC was issued. Two new DINs (02529653, 02529661) were issued. A Regulatory Decision Summary was published.
SNDS # 261584 2022-02-17 Issued NOC 2022-07-12 Submission filed as a Level II – Supplement (Safety) to update the PM with new safety information. The submission was reviewed and considered acceptable. As a result of the SNDS, modifications were made to the Adverse Reactions section of the PM, and corresponding changes were made to Part III: Patient Medication Information. An NOC was issued.
SNDS # 253993 2021-06-21 Issued NOC 2022-06-07 Submission filed as a Level I – Supplement to allow flexible dosing (maintenance dose of 300 mg every 2 weeks) in adult patients with moderate to severe plaque psoriasis. The submission was reviewed and considered acceptable, and an NOC was issued.
Drug product (DIN 02525569) market notification Not applicable Date of first sale: 2022-06-02 The manufacturer notified Health Canada of the date of first sale pursuant to C.01.014.3 of the Food and Drug Regulations.
SNDS # 252304 2021-04-30 Issued NOC 2022-04-08 Submission filed as a Level I – Supplement to update the PM with new clinical data from the MAXIMISE study, on the safety and efficacy of secukinumab in adult patients with psoriatic arthritis with axial manifestations. The submission was reviewed and considered acceptable. As a result of the SNDS, modifications were made to the Clinical Trials section of the PM. An NOC was issued.
SNDS # 250272 2021-03-10 Issued NOC 2022-03-01 Submission filed as a Level I – Supplement for a new indication and a new presentation (75 mg/0.5 mL solution for injection in pre-filled syringe). The indication authorized was: the treatment of moderate-to-severe plaque psoriasis in patients 6 years and older who are candidates for systemic therapy or phototherapy. The submission was reviewed and considered acceptable, and an NOC was issued. A new DIN (02525569) was issued for the new presentation. A Regulatory Decision Summary was published.
SNDS # 252948 2021-05-19 Issued NOC 2021-10-14 Submission filed as a Level II – Supplement (Safety) to update the PM with new safety information, and migrate it to the 2020 format. The submission was reviewed and considered acceptable. As a result of the SNDS, modifications were made to the Adverse Reactions section of the PM, and corresponding changes were made to Part III: Patient Medication Information. An NOC was issued.
SNDS # 245875 2020-11-06 Issued NOC 2021-06-02 Submission filed as a Level I – Supplement to add a manufacturing site for the production of the drug substance and drug product. The data were reviewed and considered acceptable, and an NOC was issued.
SNDS # 240496 2020-06-12 Issued NOC 2021-05-26 Submission filed as a Level I – Supplement for a new indication. The indication authorized was: the treatment of active non-radiographic axial spondyloarthritis (nr-axSpA) with objective signs of inflammation as indicated by elevated C-reactive protein (CRP) and/or magnetic resonance imagine (MRI) evidence in adults who have responded inadequately, or are intolerant to nonsteroidal anti-inflammatory drugs (NSAIDs). The submission was reviewed and considered acceptable, and an NOC was issued. A Regulatory Decision Summary was published.
SNDS # 235994 2020-02-14 Issued NOC 2021-01-20 Submission filed as a Level I – Supplement for a new indication. The indication authorized was: the treatment of severe plaque psoriasis in pediatric patients 12 to less than 18 years of age who are candidates for systemic therapy or phototherapy and have a body weight ≥50 kg. The submission was reviewed and considered acceptable, and an NOC was issued. A Regulatory Decision Summary was published.
SNDS # 232970 2019-10-29 Issued NOC 2020-10-01 Submission filed as a Level I – Supplement to allow for an up-titration in maintenance dose for ankylosing spondylitis patients from 150 mg to 300 mg, based on clinical response. The submission was reviewed and considered acceptable, and an NOC was issued.
SNDS # 219231 2018-08-15 Issued NOC 2019-07-25 Submission filed as a Level I – Supplement to update the psoriatic arthritis (PsA) indication to include a statement regarding inhibiting the progression of structural damage, and to increase the dosing from 150 mg to 300 mg for PsA patients. The change in indication was reviewed but not recommended, although the clinical trial data was added to the PM. The change in dosing was reviewed and considered acceptable, and an NOC was issued.
NC # 222964 2018-12-12 Issued NOL 2019-01-21 Submission filed as a Level II (90 day) Notifiable Change (Moderate Quality Changes) to change the working cell bank manufacturing site and introduce a new working cell bank. The submission was reviewed and considered acceptable, and an NOL was issued.
SNDS # 219397 2018-08-21 Issued NOC
2018-10-29		 Submission filed as a Level I - Supplement to abbreviate the package insert and to change text on the folding boxes. The changes to the labelling were reviewed and are considered acceptable. An NOC was issued.
SNDS # 212104 2017-12-13 Issued NOC
2018-10-12		 Submission filed as a Level I - Supplement to update the Drug Interactions section of the PM to include results from Study CAIN457A2110 and to fulfill a Post-Approval commitment (Item 14) of Health Canada's Post-Decision Letter dated March 03, 2015. The inclusion of this information in the PM does not change the previously established favourable benefit/risk ratio of secukinumab for the treatment of moderate to severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy. The submission was reviewed and considered acceptable, and an NOC was issued.
NC # 214255 2018-03-12 Issued NOL
2018-05-16		 Submission filed as a Level II (90 day) Notifiable Change (Moderate Quality Changes) to increase the batch size of the drug product, and to allow storage of the prefilled syringes by the user for a single period of up to 4 days at ≤30ºC. As a result of the NC, modifications were made to the Storage and Stability section of the PM, and corresponding changes were made to the PM Part III: Consumer Information. The submission was reviewed and considered acceptable, and an NOL was issued.
SNDS # 206826 2017-06-21 Issued NOC
2018-05-11		 Submission filed as a Level I - Supplement to update the PM with data from a Phase IIIb study in adults with moderate to severe scalp psoriasis (SCALP study). No changes to the currently authorized indications were proposed. The SCALP study provides additional supportive efficacy and safety results from a placebo-controlled trial of scalp involvement in psoriasis patients. The inclusion of this information in the PM does not change the previously established favourable benefit/risk ratio of secukinumab for the treatment of moderate to severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy. The submission was reviewed and considered acceptable, and an NOC was issued.
NC # 205774 2017-05-19 Issued NOL
2017-08-11		 Submission filed as a Level II (90 day) Notifiable Change (Risk Management Change) to update the PM with new safety information. As a result of the NC, modifications were made to the Adverse Reactions, Drug Interactions, and Dosage and Administration sections of the PM. Corresponding changes were made to the PM Part III: Consumer Information. The submission was reviewed and considered acceptable, and an NOL was issued.
SNDS # 197387 2016-08-10 Issued NOC
2017-07-28		 Submission filed as a Level I - Supplement to update the PM with data from the following Phase IIIb studies: CLEAR (CAIN457A2317 - secukinumab vs. ustekinumab), GESTURE (CAIN457A2312 - Palmoplantar psoriasis), and TRANSFIGURE (CAIN457A2313 - Nail psoriasis). The overall benefit/risk profile for Cosentyx is unchanged in this submission. However, there is a benefit to physicians and patients to include new clinical information in Part II of the PM regarding treatment of nail psoriasis and palmoplantar psoriasis. There was no change to the indications. The submission was reviewed and considered acceptable, and an NOC was issued.
NC # 201020 2016-12-08 Issued NOL
2017-02-10		 Submission filed as a Level II (90 day) Notifiable Change (Moderate Quality Changes) for an extension to the in vitro cell age. The submission was reviewed and considered acceptable, and an NOL was issued.
SNDS # 197451 2016-08-08 Cancellation Letter Received
2016-08-18		 Submission filed as a Level I - Supplement for new sample packaging. The labelling of the sample is the same as that of the trade package. A submission was therefore not necessary and it was cancelled by the sponsor.
SNDS # 184144 2015-05-07 Issued NOC
2016-04-20		 Submission filed as a Level I - Supplement for a new indication: use of Cosentyx for the treatment of adult patients with active ankylosing spondylitis who have responded inadequately to conventional therapy. Regulatory Decision Summary published.
SNDS # 184142 2015-04-30 Issued NOC
2016-04-20		 Submission filed as a Level I - Supplement for a new indication: use of Cosentyx, with or without methotrexate, for the treatment of adult patients with active psoriatic arthritis when the response to previous disease-modifying anti-rheumatic drug therapy has been inadequate. Regulatory Decision Summary published.
Drug product (DIN 02438070) market notification Not applicable Date of first sale:
2015-04-10		 The manufacturer notified Health Canada of the date of first sale pursuant to C.01.014.3 of the Food and Drug Regulations.
NDS # 170732 2013-12-17 Issued NOC
2015-02-27		 Notice of Compliance issued for New Drug Submission.
Summary Basis of Decision (SBD) for Cosentyx

Date SBD issued: 2015-04-08

The following information relates to the new drug submission for Cosentyx.

Secukinumab, 150 mg/mL, powder for solution, solution, subcutaneous

Drug Identification Number (DIN):

  • 02438062 - 150 mg/mL powder for solution
  • 02438070 - 150 mg/mL, solution

Novartis Pharmaceuticals Canada Inc.

New Drug Submission Control Number: 170732

 

On February 27, 2015, Health Canada issued a Notice of Compliance to Novartis Pharmaceuticals Canada Inc. for the drug product, Cosentyx.

The market authorization was based on quality (chemistry and manufacturing), non‑clinical (pharmacology and toxicology), and clinical (pharmacology, safety, and efficacy) information submitted. Based on Health Canada’s review, the benefit/risk profile of Cosentyx is favourable for the treatment of moderate to severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy.

1 What was approved?

Cosentyx was authorized for the treatment of moderate to severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy. Cosentyx is a fully‑human immunoglobulin (Ig) G1 monoclonal antibody that selectively binds to interleukin-17A and belongs to therapeutic class of biological response modifiers.

Cosentyx should be prescribed only by health care professionals who have sufficient knowledge of plaque psoriasis and who have fully familiarized themselves with the efficacy/safety profile of the drug.

The safety and effectiveness of Cosentyx in pediatric patients (<18 years of age) have not been evaluated.

Cosentyx is contraindicated for patients who have severe hypersensitivity reactions to the active substance or to any of the excipients. Cosentyx was approved for use under the conditions stated in the Cosentyx Product Monograph taking into consideration the potential risks associated with the administration of this drug product.

Cosentyx (150 mg/mL, secukinumab) is presented as a solution in a single-use prefilled SensoReady pen or single-use prefilled syringe, as well as lyophilized powder for solution. The important non‑medicinal ingredients are trehalose dehydrate, L‑histidine/histidine hydrochloride monohydrate, L‑methionine, polysorbate 80, and water for injection.

For more information, refer to the Clinical, Non-Clinical, and Quality (Chemistry and Manufacturing) Basis for Decision sections.

Additional information may be found in the Cosentyx Product Monograph, approved by Health Canada and available through the Drug Product Database.

2 Why was Cosentyx approved?

Health Canada considers that the benefit/risk profile of Cosentyx is favourable for the treatment of moderate to severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy.

Psoriasis is a chronic immunologic disease which affects 2 to 3% of the general population, with the highest disease prevalence in North America and Europe. Approximately 80-90% of psoriasis patients have chronic plaque psoriasis, characterized by recurrent exacerbations and remissions of thickened, erythematous, scaly patches of skin that can occur anywhere on the body. Patients with moderate to severe disease represent approximately 15% to 25% of plaque psoriasis patients and generally require systemic therapy. Several pharmaceutical drugs (including acitretin, cyclosporin, and methotrexate), and more recently several biologics (adalimumab, etanercept, infliximab, and ustekinumab) and additional pharmaceuticals [for example (e.g.), apremilast] have been authorized in Canada for the treatment of psoriasis. Each of these new biological products is accompanied by drug-specific safety concerns (e.g., infection including tuberculosis, and malignancies including lymphoma, immunogenicity and demyelinating neurologic events). In addition, none of them achieve the goal of clear/almost clear skin for a majority of patients. Thus, there remains a significant need for new mechanisms that can provide therapeutic alternatives.

Cosentyx has been shown to be efficacious for the treatment of moderate to severe plaque psoriasis. The market authorization was primarily based on 52-week safety and efficacy data from two pivotal Phase III randomized, double-blind, placebo‑controlled, multicentre studies. One of the pivotal studies also contained an active comparator, etanercept. Two other 12-week Phase III studies provided supporting data. In the pivotal studies, the 150 mg and the 300 mg dose of Cosentyx achieved greater clinical response than placebo, with skin that was clear or almost clear, as assessed by scoring of the extent, nature and severity of psoriatic changes of the skin. The 300 mg dose achieved a higher response rate compared to the 150 mg dose. Peak effects were reported at Week 16 and were sustained to Week 52 with the 300 mg dose. The improvements in the clinical response after 52 weeks of treatment were better maintained with the 300 mg dose than the 150 mg dose.

Cosentyx demonstrated a favourable safety profile. The most frequently reported adverse drug reactions were upper respiratory tract infections. Most of the events were mild or moderate in severity.

The adverse events of interest for an immunomodulatory biologic include serious infections, autoimmune disorders, major adverse cardiovascular events, and malignancies. The rates of serious infections, malignancies and serious cardiovascular events were low with Cosentyx. The incidence rates for these adverse events were similar for the two Cosentyx doses (150 mg and 300 mg) and similar to rates reported with etanercept, and placebo. However, superficial Candida infections occurred at a higher frequency with the Cosentyx 300 mg dose versus (vs.) the 150 mg dose vs. placebo (1.2% vs 0.4% vs. 0.3%, respectively). Other adverse events of concern were the 3 cases of Crohn’s disease flares reported. Appropriate warnings are included in the Cosentyx Product Monograph.

A Risk Management Plan (RMP) for Cosentyx was submitted by Novartis Pharmaceuticals Canada Inc. to Health Canada. Upon review, the RMP was considered to be acceptable. The RMP is designed to describe known and potential safety issues, to present the monitoring scheme and when needed, to describe measures that will be put in place to minimize risks associated with the product. Safety monitoring on the use of Cosentyx will be ongoing. Further evaluation will take place upon the submission of the requested studies after they become available. See the post‑approval commitments in What follow-up measures will the company take?

A Look‑alike Sound‑alike brand name assessment was performed and the proposed name Cosentyx has been deemed appropriate and acceptable.

Overall, the therapeutic benefits seen in the clinical studies are considered positive and the benefits of Cosentyx therapy outweigh the potential risks. Cosentyx has an acceptable safety profile based on the non-clinical data and clinical studies. The identified safety issues can be managed through labelling and adequate monitoring. Appropriate warnings and precautions are in place in the Cosentyx Product Monograph to address the identified safety concerns.

This New Drug Submission complies with the requirements of sections C.08.002 and C.08.005.1 and therefore Health Canada has granted the Notice of Compliance pursuant to section C.08.004 of the Food and Drug Regulations. For more information, refer to the Clinical, Non-Clinical, and Quality (Chemistry and Manufacturing) Basis for Decision sections.

3 What steps led to the approval of Cosentyx?

Submission Milestones: Cosentyx

Submission Milestone Date
Pre-submission meetings: 2013-03-07
Pre-submission meetings: 2013-07-31
Submission filed: 2013-12-17
Screening  
Screening Deficiency Notice issued: 2014-02-17
Response filed: 2014-03-18
Screening Acceptance Letter issued: 2014-05-05
Review  
On-Site Evaluation: 2015-02-02 - 2015-02-06
Quality Evaluation complete: 2015-02-27
Clinical Evaluation complete: 2015-02-27
Labelling Review complete: 2015-02-20
Notice of Compliance issued by Director General: 2015-02-27

 

Cosentyx was approved by the United States Food and Drug Administration (FDA) (2015/01/21) and was given a positive opinion by the European Medicines Agency (EMA) (2014/11/20) for the treatment of adults with moderate-to-severe plaque psoriasis. The FDA and EMA questions and responses were provided in the submission and were considered during the review. All of the sponsor’s responses and commitments to the FDA and EMA based on these questions and responses were incorporated into the Canadian submission.

For additional information about the drug submission process, refer to the Management of Drug Submissions Guidance.

4 What follow-up measures will the company take?

As part of the marketing authorization for Cosentyx, Health Canada requested and the sponsor agreed to several commitments to be addressed post-market. In addition to requirements outlined in the Food and Drugs Act and Regulations, commitments include (but are not limited to):

  • Submit to Health Canada, in accordance with Canadian Regulations, all serious adverse events including serious infections, malignancies, other autoimmune diseases, et cetra (etc.) that occurred in clinical studies with Cosentyx.
  • Provide Health Canada with an updated Canadian Risk Management Plan (RMP) to reflect the Canadian labelling and to capture the post-approval commitments to Health Canada and other regulatory agencies.
  • Provide Health Canada with Cosentyx Medical Educational materials for review prior the launch of the product.
  • Provide Health Canada with Periodic Safety Update Reports (PSURs)/Periodic Benefit Risk Evaluation Reports (PBRER) for Cosentyx annually. Include in each PSUR/PRERR an analysis of all adverse drug events that may be related to the immunogenicity profile [for example (e.g.), adverse events related to immune system disorders, skin and subcutaneous tissue disorders, etc.]; malignancies, serious infections; Crohn's disease flares and other adverse events related to the potential risks identified in the label and the RMP.
  • Include Canadian patients receiving Cosentyx in a Canadian Registry study (post-marketing observational study) and provide Health Canada with regular safety updates from this study. This should be indicated in the updated RMP requested above.
  • Provide Health Canada with regular safety updates from the ongoing clinical trials and the final reports of the studies CAIN457A2302E1 and CAIN457A2304E1 (and any other relevant studies) as soon they become available.
  • Include Canadian patients receiving Cosentyx in the planned Registry for pregnancies and provide, as appropriate, Health Canada with regular safety reports. Indicate as well this study in the updated RMP.
  • Submit to Health Canada as a Supplemental New Drug Submission (SNDS), the final report (when available) of the study to be conducted to evaluate the efficacy and safety of a higher exposure of Cosentyx (e.g. 450 mg) in psoriasis patients with higher body weight (e.g. >90 kg).
  • Submit to Health Canada, as an SNDS, the final report of the clinical study to be conducted to assess whether Cosentyx alters the metabolism or pharmacokinetics of cytochrome P450 substrates in psoriasis patients treated with Cosentyx.
  • Provide all reports/correspondence pertaining to post-approval commitments from major Regulatory Authorities [e.g. United States Food and Drug Administration (FDA), European Medicines Agency (EMA), Therapeutic Goods Administration (TGA) etc.].
5 What post-authorization activity has taken place for Cosentyx?

Summary Basis of Decision documents (SBDs) for eligible drugs authorized after September 1, 2012 will include post-authorization information in a table format. The Post-Authorization Activity Table (PAAT) will include brief summaries of activities such as submissions for new uses of the product, and whether Health Canada's decision was negative or positive. The PAAT will continue to be updated during the product's lifecycle.

The PAAT for Cosentyx is found above.

For the latest advisories, warnings and recalls for marketed products, see MedEffect Canada.

6 What other information is available about drugs?

Up to date information on drug products can be found at the following links:

7 What was the scientific rationale for Health Canada's decision?
7.1 Clinical Basis for Decision

Clinical Pharmacology

Secukinumab, the active ingredient in Cosentyx, selectively binds to and neutralizes interleukin-17A (IL-17A), a naturally occurring cytokine involved in normal inflammatory and immune responses. Interleukin-17A is highly upregulated in lesional skin in contrast to non-lesional skin of plaque psoriasis patients. Secukinumab inhibits the release of proinflammatory cytokines and chemokines, thereby reducing the signs and symptoms of the disease including erythema, pain, itching, and scaly patches.

The clinical pharmacology included reports on the human pharmacodynamic and pharmacokinetic studies. The clinical pharmacological data support the use of Cosentyx for the specified indication.

For further details, please refer to the Cosentyx Product Monograph, approved by Health Canada and available through the Drug Product Database.

Clinical Efficacy

The efficacy and safety of Cosentyx (secukinumab) were assessed in four randomized, double-blind, placebo-controlled Phase III studies (Studies ERASURE, FIXTURE, FEATURE, and JUNCTURE, also referred to as Studies 1, 2, 3, and 4, respectively). Studies 1 and 2 (the pivotal studies) provided 52-week efficacy and safety data to support the use of Cosentyx for the specified indication; treatment of moderate to severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy. Studies 3 and 4 provided 12‑week data to support the safety and efficacy of secukinumab in liquid formulation in prefilled syringes and autoinjectors (pens). The four studies had a total of 2,403 patients, 18 years of age and older, with plaque psoriasis who had a minimum body surface area involvement of 10%, a Psoriasis Area and Severity Index (PASI) score ≥12, and who were candidates for phototherapy or systemic therapy. The efficacy and safety of Cosentyx 150 mg and 300 mg were evaluated versus (vs.) either placebo or etanercept. Study 2 included the active comparator arm, etanercept.

Of the 2,403 patients who were included in the placebo-controlled studies, 79% were biologic-naïve (had no prior exposure to biologic therapy), 45% were non-biologic failures, 8% were biologic failures, 6% were anti-TNF failures (failed to respond to agents that act against tumor necrosis factor), and 2% were anti-p40 failures (failed to respond to anti-p40 antibody therapy). Baseline disease characteristics were generally consistent across all treatment groups with a median baseline Psoriasis Area Severity Index (PASI) score from 19 to 20, Investigator's Global Assessment modified 2011(IGA mod 2011) baseline score from moderate (62%) to severe (38%) and median baseline Body Surface Area (BSA) ≥27%. Approximately 15 to 25% of patients in the Phase III studies had psoriatic arthritis at baseline.

The co-primary endpoints in the placebo and active controlled studies were the proportion of patients who achieved a 75% or more reduction in their PASI score (PASI 75 response) and a clear or almost clear response with the IGA mod 2011 scale, compared with placebo at Week 12. One of the secondary endpoints was the proportion of patients who achieved a 90% or more reduction in their PASI score (PASI 90 response)

In Study 1, 71.6% and 81.6% of patients that received Cosentyx 150 mg and 300 mg, respectively, achieved a PASI 75 response at Week 12 compared with 4.5% of patients that received placebo. Also, 51.2% and 65.3% of the patients treated with 150 mg and 300 mg Cosentyx, respectively, achieved an IGA mod 2011 score of clear or almost clear compared with 2.4% of placebo-treated patients at Week 12. The PASI 90 response was achieved by 39.1% and 59.2% of the patients treated with 150 mg and 300 mg Cosentyx, respectively, compared with 1.2% of placebo-treated patients at Week 12.

In Study 2, 67% and 77.1% of patients that received Cosentyx 150 mg and 300 mg, respectively, achieved a PASI 75 response at Week 12 compared with 4.9% of patients that received placebo. Also, 51.1% and 62.5% of patients that received 150 mg or 300 mg Cosentyx, respectively, achieved an IGA mod 2011 score of clear or almost clear compared with 2.8% of the placebo patients at Week 12. Both Cosentyx doses (300 mg and 150 mg) were statistically significantly (p <0.0001) superior to etanercept at Week 12 in achieving IGA mod 2011 scores of clear or almost clear, a PASI 75 response, and achieving a PASI 90 response. At Week 12, the percentage of patients achieving a PASI 90 response was 41.9% in the 150 mg Cosentyx group, 54.2% in the 300 mg Cosentyx group, and 1.5% in the placebo group.

For all of the above efficacy endpoints, the improvements after 52 weeks of treatment were better maintained with the Cosentyx 300 mg dose compared to the 150 mg dose, and compared to etanercept. Superiority to etanercept for the PASI 75 response and the IGA mod 2011 clear or almost clear response was maintained for Week 12 responders up to Week 52.

Studies 3 and 4 provided additional efficacy data for the co-primary endpoints.

In Study 3, 69.5% and 75.9% of patients that received Cosentyx 150 mg and 300 mg, respectively, achieved a PASI 75 response at Week 12 compared with 0% of patients at that received placebo. Also, 52.5% and 69.0% of patients that received 150 mg or 300 mg Cosentyx, respectively, achieved an IGA mod 2011 score of clear or almost clear compared with 2.8% of the placebo patients at Week 12.

In Study 4, 71.7% and 86.7% of patients that received Cosentyx 150 mg and 300 mg, respectively, achieved a PASI 75 response at Week 12 compared with 3.3% of patients that received placebo. Also, 53.3% and 73.3% of patients that received 150 mg or 300 mg Cosentyx, respectively, achieved an IGA mod 2011 score of a clear or almost clear compared with 2.8% of the placebo patients at Week 12.

In summary, both doses of Cosentyx (150 mg and 300 mg) achieved the co-primary endpoints of PASI 75 response and IGA mod 2011 score of a clear or almost clear (IGA 0/1), as well as the secondary endpoint of PASI 90 in each of the pivotal studies (Studies 1 and 2). However the 300 mg dose achieved a higher response rate compared to the 150 mg dose. At the same dose, Cosentyx serum concentrations were higher in patients with a body weight <90 kg) than those in patients with a body weight ≥90 kg, and the clinical response rates were approximately 10% higher in the lower body weight group at both 150 mg and 300 mg doses (88.7% vs. 71.8% for PASI 75 and 72.5% vs. 55.3% for IGA 0/1). In addition, the 150 mg dose in patients with body weight <90 kg was shown to be as efficacious as the 300 mg dose used in those with a body weight ≥90 kg (74.3% vs. 71.8% for PASI 75 and 53.2% vs. 55.3% for IGA 0/1). Although, the use of the 300 mg dose in all patients, regardless of their body weight, is recommended, this dose might be suboptimal for patients with a body weight >90 kg. In that respect, the sponsor has committed to conduct a clinical study which will evaluate the efficacy and safety of a higher exposure of Cosentyx (e.g. 450 mg) in psoriasis patients with a higher body weight (>90 kg). See the post‑approval commitments in What follow-up measures will the company take? The sponsor will file a Supplemental New Drug Submission as appropriate if there is a need to change the dose in patients with a body weight >90 kg.

For more information, refer to the Cosentyx Product Monograph, approved by Health Canada and available through the Drug Product Database.

Clinical Safety

A total of 3,430 plaque psoriasis patients were treated with Cosentyx (secukinumab) in 10 Phase II/III clinical studies. Of these patients, 1,641 were exposed to Cosentyx for at least one year, representing 2,725 patient years of exposure.

The safety review was focussed primarily on the 52 weeks of data obtained from Studies 1 and 2, and data through to Week 12 from Studies 3, and 4. The study designs were similar for the four randomized, double‑blind placebo‑controlled Phase III studies (see the Clinical Efficacy section), therefore the safety analysis included pooling the safety data through Week 12 in the four Phase III studies. In total, 2,076 patients were evaluated (692 patients on 150 mg Cosentyx, 690 patients on 300 mg Cosentyx, 694 patients on placebo, 323 patients on etanercept).

No deaths were reported in the 12-week pooled analysis of Studies 1, 2, 3, and 4. A total of 6 deaths, assessed by the investigators as unrelated to the study drug, were reported across all of the clinical studies.

Patients treated with Cosentyx showed, during the first 12 weeks, an imbalance compared with placebo in total adverse events: 412 (60%) in the 150 mg group, 388 (56%) in the 300 mg group, compared to 340 (49%) in the placebo group. This difference was mainly driven by the incidence of events in the System Organ Class “Infections and Infestations” (29.3, 28.1 and 18.9% in the 150 mg group, 300 mg group, and placebo group, respectively). The incidence of upper respiratory tract infection was also higher in patients treated with Cosentyx (18.6% in the 150 mg group, 17.0% in the 300 mg group, vs. 10.4% in the placebo group). Superficial (oral or cutaneous) Candida infections occurred at a higher frequency with 300 mg vs. 150 mg vs. placebo (1.2% vs. 0.4% vs. 0.3%, respectively). This observation is consistent with the implied role of interleukin‑17 (IL-17) in host defense against mucosal Candida infections. No serious opportunistic infections or reactivation of latent tuberculosis or viral hepatitis were observed in any of the Phase II/III clinical studies.

During the placebo‑controlled portion of the studies, the overall incidence of malignancies was similar between each of the Cosentyx dose groups (0.1% and 0.4% for 300 mg and 150 mg, respectively) and placebo (0.4%). Over the entire treatment period in the clinical studies, the exposure adjusted rate of malignancies per 100 patient years was 0.77 and 0.97 for Cosentyx 300 mg and 150 mg compared with 0.68 for etanercept and 1.49 for placebo. In total, there were 4 cases of malignant melanoma reported (2 malignant melanoma and 2 malignant melanoma in situ). All patients had one or more of the following risk factors; prior exposure to phototherapy, tumour necrosis factor alpha (TNFα) antagonists, methotrexate, or pre-existing melanocytic nevus. No increase in the ratio of squamous cell carcinoma to basal cell carcinoma was observed.

Potential major adverse cardiovascular events (MACE, including cardiovascular death, myocardial infarction, or stroke), over the entire treatment period were reported for a similar proportion of patients on Cosentyx and etanercept; 6 (0.4%) with Cosentyx 300 mg, 5 (0.4%) with Cosentyx 150 mg, and 1 (0.3%) with etanercept. There was one MACE event also reported in the placebo group. After adjusting for exposure over the 52‑week period, the exposure‑adjusted incidence was comparable for Cosentyx, placebo, and etanercept (0.44 for Cosentyx 150 mg, 0.51 for Cosentyx 300 mg, 0.50 for placebo, and 0.34 for etanercept per 100 patient years).

Treatment-emergent anti-drug antibodies (ADAs) were detected in a total of 10 Cosentyx‑treated patients (0.4%) of which 3/10 were neutralizing antibodies. The ADAs were not associated with clinically relevant adverse events, loss of efficacy, or abnormal serum concentrations of secukinumab. There was no evidence of a dose response (300 mg: 3/1,410 = 0.2%; 150 mg: 7/1,395 = 0.5%). Emergence of anti-secukinumab antibodies was not associated with injection site reactions or serious or severe hypersensitivity adverse events.

Other serious adverse events were reported (very rarely) in the Cosentyx‑treated groups. These events included Crohn’s disease flares (3 cases) and hypersensitivity reactions including urticaria and angioedema, but no episodes of life‑threatening anaphylaxis occurred. Appropriate warnings and precautions are in place in the approved Cosentyx Product Monograph to address the identified safety concerns.

Overall, the rates of serious infections, malignancies, and serious cardiovascular events were low with Cosentyx. No dose dependency with Cosentyx in any of these events was observed. For malignancies, pre‑marketing studies are of a relatively short duration to detect such adverse events. However, the sponsor is planning to conduct a registry to provide safety updates. See the post‑approval commitments in What follow-up measures will the company take?

Based on the data presented, Cosentyx shows a positive benefit/risk profile for the treatment of moderate to severe plaque psoriasis.

For more information, refer to the Cosentyx Product Monograph, approved by Health Canada and available through the Drug Product Database.

7.2 Non-Clinical Basis for Decision

The non-clinical pharmacology and toxicology studies support the use of Cosentyx for the treatment of moderate to severe plaque psoriasis.

In repeat-dose toxicity studies, secukinumab (the medicinal ingredient of Cosentyx) was well‑tolerated following weekly intravenous doses of up to 150 mg/kg for up to 26 weeks and subcutaneous doses up to 150 mg/kg for 13 weeks. There was no evidence of treatment-related adverse findings (including infections or hypersensitivity reactions) in immunotoxicity and safety pharmacology evaluations. Immunogenicity was detected in one animal given 150 mg/kg/week subcutaneously for 13 weeks. Serum concentrations that were well‑tolerated in animals for 13 weeks of subcutaneous dosing had serum concentrations of at least 110-fold the serum concentration found in psoriasis patients at maintenance therapy, treated with a clinical dose of 300 mg subcutaneously every 4weeks.

The results of the non-clinical studies as well as the potential risks to humans have been included in the Cosentyx Product Monograph. There are no pharmacological/toxicological issues within this submission which preclude authorization of the product.

For more information, refer to the Cosentyx Product Monograph, approved by Health Canada and available through the Drug Product Database.

7.3 Quality Basis for Decision

Secukinumab, the medicinal ingredient of Cosentyx, is a fully human IgG1 monoclonal antibody with a molecular mass of 147,944 Daltons when deglycosylated.

Secukinumab selectively binds and neutralizes the proinflammatory cytokine interleukin‑17A (IL-17A). Secukinumab works by targeting IL-17A and inhibiting its interaction with the IL-17 receptor, which is expressed on various cell types including keratinocytes.

Cosentyx is supplied as a sterile solution (150 mg secukinumab in 1 mL of sterile solution) in a single-use prefilled syringe or a single-use prefilled pen. Cosentyx is also supplied as a powder for solution (requiring reconstitution for injection) in a single-use glass vial for use by healthcare professionals only.

Characterization of the Drug Substance

Extensive characterization of the physicochemical, biological, and immunological properties of the drug substance, secukinumab, and confirmation of its purity were performed using methods selected in accordance with accordance with International Conference on Harmonisation (ICH) guidelines.

Manufacturing Process and Process Controls of the Drug Substance and Drug Product

The drug substance, secukinumab, is produced in a recombinant Chinese Hamster Ovary (CHO) cell line. The manufacturing process consists of a series of steps which include cell culture, harvest, purification stages, including viral inactivation/removal steps, and formulation. Changes to the manufacturing process made throughout the pharmaceutical development are considered acceptable upon review. Data from product quality assessments, non‑clinical studies, and clinical studies demonstrate that secukinumab produced by different manufacturing process versions during development is comparable and that there has been no significant impact on quality observed due to the associated process changes. The manufacturing process has been successfully validated with five full-scale drug substance batches used to assess the removal of process-related impurities, product quality and process performance attributes, and to support the demonstration of process consistency.

The manufacturing process of the drug product, Cosentyx, a secukinumab solution for injection, consists of compounding, in-line sterile filtration of the secukinumab solution, aseptic filling of the secukinumab solution into the syringes, visual inspection, labelling, assembly, packaging and storage of the bulk medicinal product, and release of the bulk medicinal product for shipment. Suitable controls are in place particularly for verification of general characteristics, sterile filtration and adequate filling.

For the lyophilized drug product, the sponsor provided validation data for three consecutive runs from buffer formulation and thawing of the drug substance to lyophilisation of drug product vials. The sponsor has demonstrated that they are able to fill drug product aseptically with no impact to the quality attributes.

The method of manufacturing and the controls used during the manufacturing process for both the drug substance and the drug products are valid and considered to be adequately controlled within justified limits. All pre-established process validation acceptance criteria were met and the process controls assure consistent drug product manufacturing.

Control of the Drug Substance and Drug Product

The purified bulk drug substance is tested to demonstrate strength, quality, purity, potency, and identity. Analytical procedures have been carefully selected according to their ability to confirm the safety, efficacy, and activity of the secukinumab drug substance and drug product. The methods were validated in full accordance with the ICH guidelines for method validation.

The identity, quality, potency, and purity of drug product are assured by employing a similar battery of release tests used for testing of drug substance. The specifications have been set based on the process capabilities and the results from release and stability testing of clinical batches during development and considering a statistical data evaluation.

The drug substance and drug product are tested against suitable reference standards to verify that they meet approved specifications and analytical procedures are validated and in compliance with ICH guidelines.

Stability of the Drug Substance and Drug Product

Based on the stability data submitted, the proposed shelf-life and storage conditions for the drug substance and the drug product were adequately supported and are considered to be satisfactory.

The compatibility of the drug product with the container closure system was demonstrated through compendial testing and stability studies. The container closure system met all validation test acceptance criteria.

Facilities and Equipment

The design, operations, and controls of the facilities and equipment that are involved in the production are considered suitable for the activities and products manufactured.

An On-Site Evaluation (OSE) of the facilities involved in the manufacture and testing of the drug substance, secukinumab, has been successfully conducted by the Biologics and Genetic Therapies Directorate, Health Canada.

An OSE of the facility involved in the drug product manufacturing was not warranted since the facility was recently evaluated in good standing.

Adventitious Agents Safety Evaluation

The secukinumab manufacturing process incorporates adequate control measures to prevent contamination and maintain microbial control. Pre-harvest culture fluid from each lot is tested to ensure freedom from adventitious microorganisms. Purification process steps designed to remove and inactivate viruses are adequately validated.

Report a problem or mistake on this page
Please select all that apply:
Date modified: