Regulatory Decision Summary for Winrevair

This priority new drug submission sought authorization for Winrevair (sotatercept). After evaluation of the submitted data package, Health Canada authorized Winrevair for the treatment of pulmonary arterial hypertension (PAH; World Health Organization [WHO] Group 1 and Functional Class II or III) in adults, as an addition to standard of care treatments.

The submission was filed, and approved, under the Priority Review Policy.

The submission was reviewed using the international review work-sharing model with the Access Consortium. The Swiss Agency for Therapeutic Products reviewed the Drug Substance Quality and Clinical modules and the Health Science Authority (HSA) reviewed the Drug Product Quality Module. Health Canada (HC) and the Therapeutic Goods Administration (TGA) participated as peer reviewers of all modules.

The Authorization was based on a Phase 3 international, randomized, double-blind, placebo controlled trial (STELLAR). Patients (n = 323 total) with PAH (WHO Group 1) and WHO Functional Class II or III were randomized 1:1 to placebo or sotatercept. Sotatercept was provided as 0.3 mg/kg at Week 0 followed by 0.7 mg/kg every 3 weeks thereafter via subcutaneous injection. While the primary endpoint was assessed at Week 24, patients were able to remain on their assigned double-blind treatment for a long-term extension period of >60 months. The primary efficacy endpoint(s) was change from baseline in 6-minute walk distance; superiority of sotatercept over placebo was demonstrated for the primary and numerous key secondary efficacy endpoints.

Key safety risks with sotatercept include decreased platelets, increased hemoglobin, serious bleeding events, and potential negative impacts on fertility and fetal development. The most common (>5%) adverse events that occurred more frequently with sotatercept over placebo were epistaxis, telangiectasia, thrombocytopenia, hemoglobin increased, nasal congestion, headache, diarrhea, fatigue, dizziness, hypokalemia, rash, urinary tract infection, and flushing.

The recommended dose of sotatercept is 0.3 mg/kg at Week 0 followed by 0.7 mg/kg every 3 weeks thereafter via subcutaneous injection.

Health Canada granted this application priority review status.

The final decision for this product was based on the totality of evidence, including structural, functional, non-clinical, pharmacokinetic/pharmacodynamic (PK/PD) and clinical comparisons.

The chemistry and manufacturing information submitted for Winrevair has demonstrated that the drug substances and drug product can be consistently manufactured to meet the approved specifications. An Risk Management Plan (RMP) for Winrevair was reviewed by Health Canada and considered acceptable.

A Notice of Compliance was issued.

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