News from the FDA/CDC

Patisiran (Onpattro) for ATTR cardiomyopathy gets FDA panel thumbs up


The RNA interference therapeutic patisiran (Onpattro) is one step closer to being approved in the United States for treatment of transthyretin-mediated (ATTR) amyloidosis with cardiomyopathy.

The Cardiovascular and Renal Drugs Advisory Committee of the Food and Drug Administration has voted 9 to 3 that the benefits of patisiran outweigh the risks for the treatment of ATTR amyloidosis cardiomyopathy – although many panel members questioned whether the benefits are clinically meaningful.

FDA icon

ATTR amyloidosis is an underdiagnosed, rapidly progressive, debilitating, and fatal disease caused by misfolded TTR proteins, which accumulate as amyloid deposits in various parts of the body, including the heart.

Intravenously administered patisiran is already approved in the United States and Canada for the treatment of the polyneuropathy of hereditary ATTR amyloidosis in adults.

In the APOLLO-B trial, patisiran showed a statistically significant and clinically meaningful benefit on functional capacity, as measured by the 6-minute walk test, compared with placebo, in patients with ATTR amyloidosis with cardiomyopathy.

The study also met its first secondary endpoint, demonstrating a statistically significant and clinically meaningful benefit on health status and quality of life.

But in explaining her “no” vote, committee member C. Noel Bairey Merz, MD, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, said she “did not feel like there was benefit” using existing clinically relevant thresholds typically used in cardiology.

Committee chair Javed Butler, MD, MPH, Baylor Scott & White Research Institute, Dallas, who also voted no, said he “struggled” with this vote and emphasized that it “absolutely does not reflect that there is not a potential with the therapy.”

Dr. Butler said he voted no largely because he wasn’t sure whether the benefits are clinically meaningful in the context of the study design and how it was conducted. He did not have any safety concerns, which was the general feeling of the committee.

Edward Kasper, MD, Johns Hopkins University, Baltimore, who voted in favor of patisiran for ATTR amyloidosis with cardiomyopathy, said there is a “light wind for benefit and no wind for risk. So, if you’re asking do benefits outweigh the risks, the answer is yes.”

But Dr. Kasper also noted: “It would have been a more difficult question to answer: Is there clinically meaningful benefit versus risk? But that’s not what the question asked.”

In explaining his “yes” vote, Ravi Thadhani, MD, MPH, Emory University, Atlanta, said: “We’re dealing with a rare disease with few options and devastating consequences. We heard from clinicians loud and clear, and from patients for that matter, that options and alternatives are critical, and that there is a continuous decline of cardiac function and worsening of disease in a number of patients that have received the current standard of care. For me, the benefits outweigh the risks.”

Dr. Thadhani also noted that from the data provided, no benefit was shown – ”disappointingly” he lamented – for women, for Black persons, and among individuals who were receiving tafamidis, and he urged the FDA and sponsor to consider this.

The FDA has set a target action date for patisiran for ATTR amyloidosis cardiomyopathy of Oct. 8.

A version of this article first appeared on

Recommended Reading

Low-dose oral minoxidil for female pattern hair loss: Benefits, impact on BP, heart rate evaluated
MDedge Cardiology
Acoramidis shows encouraging results in ATTR cardiomyopathy
MDedge Cardiology
ESC issues new guidelines on infective endocarditis
MDedge Cardiology
Cruel summer for medical students and Taylor Swift fans
MDedge Cardiology
FDA to step up oversight of cosmetics, assess ‘forever chemicals’
MDedge Cardiology
Resident creates AI alternative to U.S. News med school ranking
MDedge Cardiology
Domestic violence in health care is real and underreported
MDedge Cardiology
ESC issues first comprehensive cardiomyopathy guidelines
MDedge Cardiology
Disenfranchised grief: What it looks like, where it goes
MDedge Cardiology
Stress, insomnia tied to increased AFib risk for older women
MDedge Cardiology