Alnylam Wins Adcomm’s Support for Heart Disease Drug Despite FDA Concerns

Pictured: FDA headquarters, iStock, Grandbrothers

Pictured: FDA headquarters, iStock, Grandbrothers

The FDA’s Cardiovascular and Renal Drugs Advisory Committee on Wednesday voted 9-3 in favor of Alnylam Pharmaceuticals’ patisiran on whether its benefits outweigh its risks for the treatment of adults with cardiomyopathy induced by transthyretin amyloidosis.

In the company’s announcement on Wednesday, Alnylam CMO Pushkal Garg said the “positive outcome” of the adcomm meeting is “supported by the efficacy and safety data observed in the APOLLO-B Phase III study and is another step toward bringing patients with the cardiomyopathy of ATTR amyloidosis a novel treatment option that addresses the underlying cause of disease and has the potential to meaningfully benefit patients’ functional capacity and quality of life.”

The decision came after the panel’s day-long meeting in which adcomm members discussed whether the treatment effects demonstrated by data from Alnylam’s Phase III APPOLLO-B clinical trial were clinically meaningful for patients with cardiomyopathy induced by transthyretin amyloidosis (ATTR-CM).

However, major discussion points during the meeting included whether the primary and secondary endpoints used by Alnylam were appropriate to ascertain clinical meaningfulness in the ATTR-CM population. The data in question was measured by the 6-Minute Walk Test (6MWT) and the Kansas City Cardiomyopathy Questionnaire Overall Summary (KCCQ-OS) score, respectively.

The committee expressed varying opinions on whether the magnitude of the benefit seen in trial data was clinically meaningful, with some members generally in agreement that the 6MWT and KCCQ-OS scores were not appropriate endpoints to ascertain clinical meaningfulness. Ultimately, the vast majority of panel members voted that the benefits of patisiran outweighed its risks, pointing to its favorable safety profile.

David Cella, an adcomm member from the Northwestern University Feinberg School of Medicine, said during Wednesday’s meeting that his “yes” vote was based on the fact that “it’s like a light wind blowing in favor of patisiran over placebo,” as reported by STAT News.

Edward Kasper, an adcomm member from the Johns Hopkins School of Medicine, similarly said “there is a light wind for benefit and no wind for risk,” according to Fierce Pharma.

The APOLLO-B trial did not show a benefit to mortality or irreversible morbidity. Still, during the public hearing portion of the meeting, the Amyloidosis Research Consortium presented data that showed ATTR-CM patients are more concerned with extending the length of their life and slowing the progression of their disease than they are with rare, but serious complications from the treatment.

FDA guidance recommends that anchor-based methods are used in clinical trials to directly incorporate patient perspectives to help interpret the clinical meaningfulness of clinical outcome assessment-based endpoints. The APOLLO-B trial did not employ appropriate anchor scales nor was qualitative data collected to evaluate the clinical meaningfulness of the 6MWT or the KCCQ-OS score, according to the FDA’s briefing document released on Monday ahead of the meeting.

The regulator in its briefing document noted that the effects of patisiran, as compared to placebo on the endpoints, were “small, of questionable clinical meaningfulness, and may not be detectable by patients.”  

The FDA has set a PDUFA target action date of Oct. 8, 2023. While the adcomm’s vote is not binding, if approved by the regulator, patisiran would become the second therapy available to ATTR-CM patients.

Another point of discussion during Wednesday’s adcomm meeting was whether the clinical trial data supported the use of patisiran as a monotherapy or in combination with tafamidis, Pfizer’s approved therapy for treating ATTR-CM. A clear answer was not reached by the committee with some members pointing out that disease progression still occurs with tafamidis treatment, while others felt that tafamidis should still be used as a first-line treatment.

Hayley Shasteen is a freelance science writer based in northeastern Ohio. You can reach her at, or follow her on LinkedIn.

Back to news