FDA advisory committee endorses Onpattro for ATTR cardiomyopathy
Treatment is approved for related condition, familial amyloid polyneuropathy
A committee of the U.S. Food and Drug Administration (FDA) has endorsed Onpattro (patisiran) for the treatment of the ATTR amyloidosis with cardiomyopathy (ATTR-CM), or heart damage.
Earlier this year, Alnylam Pharmaceuticals, which is developing Onpattro, submitted a supplemental new drug application (sNDA) to the federal agency seeking to expand the therapy’s label to include ATTR-CM. The treatment is currently indicated for the related condition familial amyloid polyneuropathy (FAP).
The committee, called the Cardiovascular and Renal Drugs Advisory Committee (CRDAC), is an independent panel that provides the FDA with advice on marketed and experimental medicines for cardiovascular and kidney disorders. It voted 9 to 3 that Onpattro’s benefits outweigh its risks for ATTR-CM. While the panel’s vote is not binding, the FDA will consider it when making a decision, which is expected by Oct. 8.
“We are grateful for the CRDAC’s thoughtful review and discussion, and thank the patients, physicians and advocacy community who shared their valuable insights today,” Pushkal Garg, MD, Alnylam’s chief medical officer, said in a company press release. “We look forward to continuing to work with the FDA as they complete their review of our sNDA.”
ATTR amyloidosis is a group of conditions in which the transthyretin (TTR) protein forms toxic clumps that accumulate in body tissues. One such condition, called FAP or hereditary ATTR amyloidosis with polyneuropathy, is characterized by damage in the nerves outside the brain and spinal cord.
Another of these conditions, ATTR-CM, which can be hereditary or not, is marked by heart damage.
Onpattro designed to lower levels of toxic protein clumps and ease symptoms
Onpattro, administered by infusion directly into the bloodstream, is designed to reduce TTR protein levels by interfering with an intermediate molecule in TTR production. As such, the therapy is expected to lower the levels of toxic protein clumps and ease symptoms.
The committee’s favorable decision was supported by data from the Phase 3 APOLLO-B clinical trial (NCT03997383). Launched in 2019, the trial enrolled 360 adults with ATTR-CM who were randomly assigned to receive either 0.3 mg/kg of Onpattro or a placebo, given once every three weeks for about a year.
Top-line results showed that Onpattro significantly slowed the decline in exercise capacity, as measured by the distance walked in six minutes (6MWD), compared with a placebo. People with cardiomyopathy typically experience lower exercise capacity scores over time.
The therapy also significantly outperformed the placebo in preventing a worsening of quality of life, as indicated by the Kansas City Cardiomyopathy Questionnaire Overall Summary.
Onpattro’s safety profile in APOLLO-B was consistent with that reported in previous studies, with upper respiratory tract infections and infusion-related reactions as the most commonly reported adverse events.
Participants who completed the trial’s placebo-controlled part were invited to enroll in its open-label extension (OLE) portion. All are receiving Onpattro for up to three additional years.
An interim analysis after six months of the OLE showed that 6MWD declines were slower for those assigned initially to Onpattro versus those who were switched from the placebo after a year.
Also, patients who’d been treated with Onpattro for 1.5 years had stable markers of heart stress and injury and maintained quality of life. In contrast, participants initially on the placebo saw declines in these measures after six months in the OLE.
“The positive outcome of today’s meeting is supported by the efficacy and safety data observed in the APOLLO-B Phase 3 study,” Garg said. It 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.”