Regulatory Decision Summary for Onpattro

Review decision

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.


Product type:

Drug

Medicinal ingredient(s):

patisiran

Therapeutic area:

Other Nervous System Drugs

Type of submission:

Priority New Drug Submission (New Active Substance)

Control number:

221896
What was the purpose of this submission?

 

This New Drug Submission (NDS) was filed to obtain market authorisation for Onpattro in the treatment of hereditary transthyretin-mediated amyloidosis (hATTR amyloidosis) with polyneuropathy in adults. This NDS was reviewed under the Priority Review policy.

 

Why was the decision issued?

 

The safety and effectiveness of Onpattro (patisiran) in the treatment of polyneuropathy associated with hereditary transthyretin-mediated amyloidosis (hATTR-PN) was assessed in a clinical development program comprising six clinical studies, including one pivotal, randomised, double-blind, placebo-controlled, Phase 3 trial, Study 004 (the APOLLO Study). Two long-term open-label extension trials were also conducted. Patients had hATTR-PN ranging in severity from mild disease to severe motor, sensory, and autonomic dysfunction.

The primary pre-specified efficacy analysis showed a statistically significant and clinically relevant change from baseline favouring Onpattro over placebo in the modified Neurologic Impairment Score (mNIS+7) after 18 months of treatment (34.0 point improvement in mNIS+7 score relative to placebo, p<0.001), with benefit apparent after 9 months of treatment. Change from baseline in the key secondary endpoint of the Norfolk Quality of Life-Diabetic Neuropathy (QoL-DN) total score, a patient-reported score that assesses neuropathy parameters and activities of daily living, also favoured patisiran at 18 months (21.1 point improvement in Norfolk QoL-DN score relative to placebo, p<0.001), with improvement also evident at 9 months. Statistically significant improvements were also seen at 18 months compared to placebo for a variety of other neurologic endpoints, including measurement of motor strength (NIS-weakness), patient-reported ability to perform activities of daily living (Rasch-Built Overall Disability Scale), gait speed (10-meter walk test), nutritional status (modified body mass index), and patient-reported autonomic symptoms such as dizziness, constipation, diarrhea, nausea/vomiting, and incontinence (Composite Autonomic Symptom Score 31). Interim analyses of the long-term open-label extension trial, Study 006, are consistent with continued benefit of Onpattro treatment on neuropathy endpoints.

The overall safety profile of Onpattro is considered favourable for use in the treatment of polyneuropathy in adults with hATTR-PN. Onpattro was generally well-tolerated, with the only major risk identified being infusion-related reactions (IRRs). In the APOLLO Study a 10% absolute increase in the incidence of IRRs was seen with patisiran treatment compared to placebo. The IRR adverse events were generally mild or moderate in severity, and resolved over time, with a single patient discontinuing Onpattro due to flushing. All patients were pretreated with acetaminophen and intravenous corticosteroids and H1 and H2 blockers at least 60 minutes prior to receiving their Onpattro infusion, as specified in the Onpattro Product Monograph.

Important identified potential risks of Onpattro include vitamin A deficiency and severe hypersensitivity reactions. Neither of these were observed in the clinical development programme for Onpattro, however all patients received daily vitamin A supplementation during the studies. The Product Monograph also recommends vitamin A supplementation during Onpattro therapy.

A Risk Management Plan (RMP) for Onpattro was submitted to Health Canada by the sponsor, and following review by the Marketed Health Products Directorate was considered to be acceptable.

Based on the above, it is considered that the evidence demonstrates that Onpattro provides a benefit on slowing hATTR polyneuropathy progression, with an acceptable safety profile.

 

Decision issued

Approved; issued a Notice of Compliance in accordance with the Food and Drug Regulations.