ALS is a fatal neurodegenerative condition that affects chewing, talking, and walking, progresses to paralysis, and culminates in respiratory failure, typically within three to five years. An estimated 30,000 Americans live with ALS, sometimes called Lou Gehrig’s disease. On Sept. 29, the Food and Drug Administration approved Relyvrio from Amylyx Pharmaceuticals. It’s the first ALS medication to be approved in five years and only one of three currently prescribed to patients to slow the progression of the disease, but should it have been approved?
(Summary from Daily Beast) An FDA advisory committee voted 7-2 in favor of recommending the drug’s approval after a single phase 2 trial of 137 ALS patients found Relyvrio could help patients survive an estimated 10.6 more months, according to Amylyx’s analyses. That may not seem very much for the average person, but “10 months can mean going to a wedding. It can mean seeing the birth of a child or graduation,” Calaneet Balas, CEO and president of the ALS Association told The Daily Beast.
The FDA typically doesn’t sign off on new drugs until after phase 3 clinical trials to assess whether a drug provides a better benefit than currently available. Relyvrio’s approval was based on a single, relatively small, reasonably short phase 2 trial—unusual even for priority review, said Richard Bedlack, a neurologist at Duke University who supports the approval.
The FDA itself admitted in a summary memorandum on Relyvrio’s approval that when it comes to the drug’s clinical trial results, “there are limitations to these findings that result in a degree of residual uncertainty about the evidence of effectiveness.”. “In terms of establishing the conclusion that it’s effective, we were asked to look for substantial evidence with persuasiveness and robustness, and I think this one trial doesn’t quite meet that bar,” committee member Dr. Kenneth Fischbeck, who studies hereditary neurological diseases at the National Institutes of Health, stated at the March meeting.
However, the committee was asked to reconsider its verdict this September after Amylyx provided additional analyses accounting for placebo crossover (when placebo participants are later offered the active drug to reassess survival rate) and how survival rates compared to disease data from the 1990s. “It was estimated that the actual survival benefit may be longer than the originally reported five months, but closer to 10 or 11 months,” Dr. Sabrina Paganoni, a physician-scientist at the Healey Center for ALS at Massachusetts General Hospital who led Amylyx’s phase 2 trial.
“The manufacturer provided reanalysis of data that was already in hand, as well as a variety of post hoc analyses,” Caleb Alexander, an epidemiologist at Johns Hopkins University, told The Daily Beast.
Amylyx has said it is committed to eliminating the co-pay for privately insured patients, and a spokesperson said, “we are working to ensure that people with government-funded insurance, like Medicare or Medicaid, will have access to Relyvrio as quickly and efficiently as possible.”
The Boston-based Institute for Clinical and Economic Review, a nonprofit watchdog of drug costs, has said the list price for the drug “far exceeds” cost-effectiveness measures. It was recommended in September that Relyvrio should be priced between $9,100–$30,700 per year.
The high costs are especially confusing considering that Relyvrio is a combination of two drugs that many patients already self-administer as a DIY cocktail: sodium phenylbutyrate, which is available on Medicare, and taurursodiol, which can be ordered online.The Daily Beast
“This is a deterioration of the FDA from requiring two studies to requiring just one study—a smaller study, a shorter-term study, a study that doesn’t even meet the agreed upon outcome,” Diana Zuckerman, a health analyst at the National Center for Health Research, told The Daily Beast. “Even if the U.S. enrollment in the [phase 3] study is completed, that doesn’t mean the follow-up has been completed,” Zuckerman said at the Sept. 7 hearing, referencing potentially low-uptake of trial volunteers if Relyvrio is publicly available.
Is this another huge mistake by the FDA, or is it hope for ALS patients? Will the FDA follow up on future clinical studies?
A diagnosis of ALS is devastating and offers little hope for patients and caregivers, but with more drugs on the horizon, we can hope that some relief is on the way but at what cost? The other issue is that it may provide a false promise to patients, but the FDA believes some glimmer of hope is better than none.