A panel of expert advisers to the Food and Drug Administration on Wednesday concluded that the benefits of a drug from Alnylam Pharmaceuticals outweighed its risks in the treatment of a form of cardiomyopathy, a disease of the heart muscle.
Despite the 9-3 vote, the panel stopped short of recommending that the FDA expand the use of the drug Onpattro beyond its current approval to treat a related peripheral nerve disease called polyneuropathy. The experts agreed with FDA scientists that Onpattro’s benefits to cardiomyopathy patients in a clinical trial compared to a placebo were modest at best and might not be enough to warrant FDA approval without further study.
The FDA doesn’t have to follow the advice of its independent advisory committees but usually does. The agency is expected to make a decision on expanding the use of Onpattro by Oct. 8.
The only approved treatment for the heart disease, called ATTR-CM, is a Pfizer drug called tafamidis. It generated about $2.5 billion in sales last year. Alnylam, which is based in Cambridge, views Onpattro as a potential rival to Pfizer’s blockbuster drug.
But members of the FDA’s Cardiovascular and Renal Drugs Advisory Committee said Alnylam hadn’t made a particularly compelling case for Onpattro as an alternative to Pfizer’s drug.
“This is a bunt single versus the home run of tafamidis,” said Dr. Christopher M. O’Connor, a professor of medicine at Duke University.
Alnylam characterized the vote as a “positive outcome.” In a statement, Alnylam’s chief medical officer, Dr. Pushkal Garg, said, “We look forward to continuing to work with the FDA as they complete their review.”
The lukewarm reception by the expert panel came despite passionate comments from about a dozen patients who said they received Onpattro in clinical trials and that it halted progression of the heart disease, or even reversed it. ATTR-CM often leads to heart failure and sometimes necessitates heart transplants.
“I would argue vehemently that the drug is working,” said Ozzie Giglio, a 62-year-old Navy veteran and fitness enthusiast who said he has been able to resume climbing stairs and doing pushups. “What this treatment means for me and other patients who need this option is hope, promise, and time.”
In a pivotal study, Onpattro met its primary study goal by helping patients walk about 14.7 meters more over the course of six minutes compared to those given a placebo. Alnylam said that was a statistically significant difference suggesting the medicine is preventing the debilitating advance of the disease.
US regulators, however, signaled in briefing documents released Monday that they were less impressed.
Onpattro’s effects compared to a placebo “were small, of questionable clinical meaningfulness, and may not be detectable by patients,” regulators wrote in documents. Regulators identified no major safety concerns.
Onpattro was initially approved in 2018 as a first-of-its-kind treatment for a related genetic disease called hereditary transthyretin amyloidosis, or hATTR, with polyneuropathy that is characterized by the buildup of abnormal proteins in peripheral nerves. Several experts say the polyneuropathy and cardiomyopathy are manifestations of the same disease.
Onpattro is given as an infusion and was the first in a class of drugs that rely on RNA interference, or RNAi, a Nobel Prize-winning approach to mute disease-causing genes.
One of the trial investigators for Alnylam, Dr. Ronald Witteles, urged the advisory panel to recommend that Onpattro’s use be expanded to include cardiomyopathy, saying the study produced “clear efficacy data.”
“The fact that we can slow this decline,” said Witteles, a cardiologist at Stanford Medicine, “is absolutely clinically meaningful.”
However, several panel members weren’t convinced that Onpattro would be an improvement over tafamidis, which was approved in 2019. After an average of 30 months, the survival rate was higher in patients who received the Pfizer drug than in a placebo, the FDA said when it cleared tafamidis. The drug was also shown to reduce the number of hospitalizations for cardiovascular problems.
Jonathan Saltzman can be reached at firstname.lastname@example.org.