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Lessons From the Withdrawal of the Amyotrophic Lateral Sclerosis Drug AMX0035 (RELYVRIO)

Health Letter, May 2024

By Robert Steinbrook, M.D.
Director, Public Citizen's Health Research Group

In April 2024, Amylyx Pharmaceuticals announced that it would withdraw AMX0035 (sodium phenylbutyrate and taurursodiol, sold under the brand name RELYVRIO) from the market. In 2022, the Food and Drug Administration (FDA), heeding passionate pleas from some patients and physicians and disregarding concerns that the data supporting the effectiveness of AMX0035 were inconclusive, had approved the drug for the treatment of amyotrophic lateral sclerosis (ALS) in adults. The drug is administered orally or via feeding tube once daily for three weeks and twice daily thereafter.

ALS is a devastating progressive neurodegenerative disease affecting nerve cells in the brain and spinal cord; effective treatments are urgently needed. The median survival time from disease onset to death ranges from 20 to 48 months. But AMX0035 was never the answer for ALS patients, the enthusiasm of its supporters notwithstanding.

In 2022, Public Citizen urged the FDA not to approve AMX0035 because the data from a single phase 2 clinical trial of 137 subjects and its open-label extension study were inconclusive. In March 2024, the company announced that the drug did not provide any benefit to ALS patients in a 48-week, randomized, placebo-controlled phase 3 clinical trial of 664 subjects. According to a company press release, the study, known as Phoenix, “did not meet its primary endpoint of reaching statistical significance (p=0.667) as measured by change from baseline in the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) total score at Week 48, nor was there statistical significance seen in secondary endpoints.” The ALSFRS-R allows clinicians to rate a patient’s function in activities of daily living such as swallowing, dressing and hygiene, and climbing stairs; the rate of decline of the score can be used to predict a patient’s survival time. As the typical threshold for statistical significance is a p value of <0.05, a value of 0.667 means that the drug provided no benefit. As of this writing, the Phoenix study has neither been presented at a medical meeting nor published in a medical journal. Before approving a drug, the FDA typically requires convincing evidence from two or more Phase 3 clinical trials.

The FDA’s approval of AMX0035 allowed Amylyx to make tens of millions of dollars in profits from selling a drug that turned out to be worthless. According to STAT, Amylyx charged $163,000 a year for AMX0035, leading to $381 million in sales and $49 million in profits in 2023. About 4,000 patients in the United States have received the treatment. Individuals and payors needlessly spent hundreds of millions of dollars unjustly enriching the company. All these consequences were preventable, and the FDA needs to take steps to ensure that it never again approves a drug without clear evidence of efficacy. And although listening to patients and advocacy groups is important, listening has its limits, particularly when the financial associations between large pharmaceutical companies and disease-specific organizations and physicians are considered.