FDA rejects Alnylam bid to expand drug
The Food and Drug Administration refused to expand its approval of a gene-silencing medicine from Alnylam Pharmaceuticals to treat a rare progressive heart disease after concluding that the benefits to patients weren’t “clinically meaningful,” the firm said Monday.
Yvonne Greenstreet, Alnylam’s chief executive, told analysts in a conference call that she was “quite surprised” by the FDA decision, which was received in a letter to the Cambridge company. She said Alnylam designed the study of the medicine, called Onpattro, with regulators and the drug met multiple goals in a clinical trial.
In a pivotal study, she said, Onpattro met its primary goal by helping patients with the debilitating disease, called ATTRCM, walk about 14.7 meters more in six minutes compared to those given a placebo. Alnylam said that was a statistically significant difference suggesting the medicine was slowing the progression of the deadly disease.
Alnylam’s share price on the Nasdaq fell about 5 percent Monday to close at $168.32.
As a result of the FDA decision, Greenstreet said, Alnylam will no longer pursue expanded use of Onpattro for ATTR-CM, a progressive form of cardiomyopathy that causes abnormal proteins to build up in the heart and can lead to heart failure if left untreated.
“We are extremely disappointed with this outcome,” Greenstreet said. “This is a fatal disease that robs patients of their ability to lead a normal life. . . . These patients need new treatment options.”
FDA staffers had taken a dimmer view of the company’s study results. In briefing documents made public last month, regulators said Onpattro’s effects compared to a placebo “were small, of questionable clinical meaningfulness, and may not be detectable by patients.” Regulators identified no major safety concerns.
The agency had cleared Onpattro in 2018 as a novel treatment for a related genetic disease called hereditary transthyretin amyloidosis, or hATTR, with polyneuropathy. That disorder causes the buildup of proteins in peripheral nerves.
Alnylam is hoping that another one of its medicines, Amvuttra, which was approved last year for the same peripheral nerve conditions, generates positive results in a late-stage clinical trial for the heart disease early next year. The ongoing Amvuttra clinical trial is twice as big as the Onpattro study was and has been running three times as long, Greenstreet said.
An independent panel of expert advisers to the agency on Sept. 13 voted 9-3 that the benefits of Onpattro outweighed its risks in the treatment of ATTRCM. Nonetheless, members of the committee were clearly underwhelmed and said the trial results were much less impressive than those generated by a Pfizer drug called tafamidis, the only approved treatment for ATTR-CM. Tafamidis generated about $2.5 billion in sales last year. Alnylam considered Onpattro a potential rival to Pfizer’s blockbuster drug.
“This is a bunt single versus the home run of tafamidis,” Dr. Christopher M. O’Connor, a professor of medicine at Duke University, one of the FDA advisers, said at the committee meeting.
Given as an infusion, Onpattro was the first drug approved in a new class of medicines that rely on RNA interference, or RNAi, a Nobel Prize-winning approach to mute disease-causing genes. Alnylam has persuaded drug regulators to approve five RNAi drugs for rare diseases. The medicines, which have annual list prices of six figures per patient, work by silencing disease-causing genes in the liver.
Alnylam is one of the state’s biggest homegrown drug firms by headcount, with 1,159 employees in Massachusetts, according to a report last month by the nonprofit Massachusetts Biotechnology Council trade group.
‘We are extremely disappointed with this outcome . . . These patients need new treatment options.’
YVONNE GREENSTREET
Alnylam chief executive