Patient advocacy groups should stay out of drug approvals | GUEST COMMENTARY

Pharmaceutical company Amylyx has been applauded for keeping its promise to withdraw Relyvrio, a drug for ALS (amyotrophic lateral sclerosis), after the drug failed a post-approval clinical trial. The real story is that evidence never supported the drug’s approval in the first place. A drug company shouldn’t be in the position to decide to sell a drug that has not been shown to be effective. Only effective drugs should receive full approval.

The Food and Drug Administration (FDA) approved Relyvrio on the basis of a single study with limited data and questionable benefits — no one improved, but the drug possibly slowed decline. After approval in 2022, Amylyx marketed Relyvrio at a price of $158,000 per year, while conducting a trial to determine that the drug worked. Relyvrio sales for 2023 brought in $381 million and earned Amylyx $49 million in profits.

The FDA generally requires results from two well-designed clinical trials for approval; results in one study could be due to chance. Historically, the FDA rarely considered one clinical trial convincing evidence. No one should have found Amylyx’s single study persuasive.

The FDA certainly wasn’t convinced in 2020 when they discouraged Amylyx from seeking approval without a large, confirmatory trial. Nor were they in October 2021, when Amylyx applied for approval based on their preliminary study of 137 patients. The FDA reiterated concerns about the potential for unblinding of patients, missing data and biased reporting. The FDA’s own analysis of the data indicated the drug was ineffective. In March 2022, an advisory committee agreed, voting 6-4, against approval.

The FDA maintained that one poor study was not enough for approval, despite unrelenting pressure from patient advocacy groups arguing otherwise. The ALS Association had supported Relyvrio’s development with $2.2 million in grants to Amylyx and a repayment clause that offered the association up to 150% of its investment if Relyvrio became profitable. Both the ALS Association and the I AM ALS organization, working together and separately, campaigned for approval by petitioning the FDA, lobbying Congress, and organizing a congressional hearing.

After the advisory committee voted against the drug in March 2022, the ALS Association ratcheted up its campaign, forcing the FDA to convene a highly unusual second advisory committee meeting in September. This time, moved by the orchestrated testimony of family members, patients, and clinicians, as well as Amylyx’s promise to remove the drug should a confirmatory trial fail, the committee voted 7-2 to support approval. The FDA approved Relyvrio later that same month.

This may be part of a bad trend. The FDA has been approving more and more drugs with limited data. A study of novel drugs approved in 2022 found that 65% of approvals were based on a single trial, in contrast to only 20% in 2016. Those drugs are unlikely to have successful confirmatory trials. According to one study, less than one third of new drugs approved “on the basis of a single pivotal trial had at least one post-approval trial showing superior efficacy.”  

Although Relyvrio is now off the market, we can expect other ineffective drugs to be championed by conflicted ALS groups. In recent weeks, the FDA gave Brainstorm Cell Therapeutics permission to perform another trial of its biologic NurOwn on a selected subset of ALS patients. I AM ALS has rallied behind NurOwn, even after a study failed to meet efficacy endpoints and the FDA rejected the biologic’s application in 2022. When Brainstorm persisted, filing their application “over protest”, I AM ALS and other patient advocacy groups hand-delivered a petition “with over 30,000 signatures” to secure an FDA advisory committee hearing in 2023. The advisory committee voted 17-1 against NurOwn, and Brainstorm withdrew its application, but the company is still trying to save the failed therapy.

It’s conceivable that Relyvrio’s approval in the midst of the NurOwn saga may have emboldened Brainstorm to push forward even after a failed trial. Conflicted advocacy groups can be counted on to support yet another inadequate drug. Let’s hope the FDA will stick to the evidence and not be bullied; ALS patients deserve better than to end up with a repeat of Relyvrio.

The FDA’s regulatory strategy shouldn’t rely on a company to voluntarily remove an ineffective drug. Patients and advocacy groups may be eager to have new drug treatments, but approving drugs without adequate data doesn’t serve anybody. Drug companies make money selling drugs whether they work or not. When they don’t, patients and taxpayers pay the price without benefit. The FDA should have approval standards that protect patients.

Judy Butler (jb2826@georgetown.edu) is a research fellow at PharmedOut, a research and education project at Georgetown University Medical Center. Caroline Renko (cr1082@georgetown.edu) is a project manager at PharmedOut. And  Adriane Fugh-Berman (ajf29@georgetown.edu) is a professor in the departments of Pharmacology, Physiology and of Family Medicine at Georgetown University Medical Center, where she’s also the director of PharmedOut. Dr. Fugh-Berman is a paid expert witness on behalf of plaintiffs in litigation regarding pharmaceutical and medical device marketing practices. Other authors have no conflicts of interest.