Regulatory Decision Summary for Siliq
The Regulatory Decision Summary explains Health Canada’s decision for the product seeking market authorization. The Regulatory Decision Summary includes the purpose of the submission and the reason for the decision.
Type of submission:
What was the purpose of this submission?
The purpose of this submission was to seek marketing authorization in Canada for Siliq (brodalumab) for the treatment of moderate to severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy
This was the first submission for Siliq in Canada.
Why was the decision issued?
Plaque psoriasis (PsO) is a chronic immunologically-mediated disease in which the marked inflammation and thickening of the epidermis result in thick, red, scaly plaques involving the skin. Plaques are most commonly found on the elbows, knees, scalp, and back. The disease is characterized by exacerbations and remissions that often seem to occur spontaneously. PsO affects 1% to 3% of the general population, with the highest disease prevalence in North America and Europe. The severity of plaque psoriasis was graded as mild and moderate-to-severe disease.
The clinical efficacy results for Siliq are based on clinical data from three multicenter, randomized, double-blind, controlled trials (Trials 1, 2, and 3) that enrolled a total of 4,373 subjects 18 years of age and older with at least a 6-month history of moderate to severe PsO. In all three trials, the co-primary endpoints (compared to placebo) were the proportion of subjects who achieved a PASI score of 75 (PASI 75) and static Physicians Global Assessment success ("sPGA success") at Week 12. The primary endpoint (compared to ustekinumab) for Trials 2 and 3 was the proportion of patients who received brodalumab and achieved a PASI score of 100
Siliq was superior to placebo and/or ustekinumab in all three clinical trials for the co-primary endpoint and for key secondary endpoints. The onset of response as measured by PASI 75 was observed within 2 weeks of treatment with brodalumab in all three clinical trials. Quality-of-Life outcomes were consistent with physician- reported outcomes. The majority of brodalumab patients who were responders at Week 12 maintained this response at Week 52.
The safety profile of Siliq in the target population, as evaluated in over 4,400 psoriasis patients over 52 weeks of treatment, is acceptable. Important identified risks for brodalumab are: worsening of active Crohns disease, infections, and neutropenia. Important potential risks are: suicidal ideation and behaviour (SIB), major adverse cardiovascular events (MACE), and hypersensitivity. A causal relationship between brodalumab and SIB was not demonstrated but cannot be excluded. An Enhanced Pharmacovigilance Plan and a Siliq Patient Support Program will be implemented to mitigate SIB risk.
The benefits of Siliq, in the target population and for the indication sought, outweigh its known risks. The overall benefit/risk profile of Siliq is considered to be favourable.
Post-marketing commitments include: the development of educational materials for Siliq patients and caregivers; the implementation, in addition to the Enhanced Pharmacovigilance Plan and the Patient Support program, of additional measures to minimize the risk of SIB for Siliq patients in Canada and to assess the effectiveness of these measures; and submission to Health Canada, in a timely manner, of results from additional planned studies with Siliq, as well as Periodic Benefit/Risk Assessment Reports (PBRER) for Siliq.
For more information on Health Canadas decision, please view the Summary Basis of Decision.
Approved; issued a Notice of Compliance in accordance with the Food and Drug Regulations.