Adcomm Backs Alnylam’s Heart Disease Drug Despite FDA Concerns: A Close Vote with Patient Perspective in Focus”
In a closely-watched decision, the FDA’s Cardiovascular and Renal Drugs Advisory Committee voted 9-3 in favor of Alnylam Pharmaceuticals’ patisiran for the treatment of adults with cardiomyopathy induced by transthyretin amyloidosis, even in the face of FDA concerns.
Alnylam’s Chief Medical Officer, Pushkal Garg, hailed the “positive outcome” of the adcomm meeting, citing the efficacy and safety data from the APOLLO-B Phase III study as a significant step toward providing a novel treatment option for patients with this rare disease, potentially improving their functional capacity and quality of life.
The day-long meeting saw adcomm members deliberating the clinical significance of the data from Alnylam’s Phase III APPOLLO-B trial for patients with cardiomyopathy induced by transthyretin amyloidosis (ATTR-CM). One key discussion point was whether the trial’s primary and secondary endpoints, the 6-Minute Walk Test (6MWT) and the Kansas City Cardiomyopathy Questionnaire Overall Summary (KCCQ-OS) score, were appropriate measures of clinical meaningfulness for this patient population.
Opinions on the magnitude of the benefit seen in the trial data varied among committee members, particularly concerning the suitability of the 6MWT and KCCQ-OS scores as endpoints. Despite these differences, the majority of panel members ultimately voted in favor of patisiran, citing its favorable safety profile.
Some committee members likened their votes to a gentle breeze in favor of patisiran over placebo, emphasizing the perceived benefits outweighed the risks. However, the APOLLO-B trial did not demonstrate a benefit in terms of mortality or irreversible morbidity.
During the public hearing, the Amyloidosis Research Consortium presented data showing that ATTR-CM patients prioritize extending their life and slowing disease progression over concerns about rare complications from treatment.
FDA guidance recommends using patient perspectives to assess the clinical meaningfulness of clinical outcome assessment-based endpoints, but the APOLLO-B trial did not follow these guidelines. The FDA’s briefing document raised doubts about the clinical significance of patisiran’s effects compared to placebo, suggesting they might be too small to be detected by patients.
The FDA’s decision on patisiran is expected by October 8, 2023. If approved, it would become the second therapy available to ATTR-CM patients.
Another point of discussion during the meeting was whether patisiran should be used as a monotherapy or in combination with tafamidis, Pfizer’s approved therapy for ATTR-CM. The committee did not reach a definitive conclusion, with some members highlighting the continued disease progression with tafamidis, while others suggested it should remain a first-line treatment option.