FDA approves new ALS drug tested in clinical trial at UF

By Michelle Jaffee

The U.S. Food and Drug Administration on Thursday approved the first new drug in five years to treat ALS, also known as Lou Gehrig’s disease, following a multisite clinical trial that included the University of Florida.

Doctor James Wymer
Dr. James Wymer

“ALS is a progressive, neurodegenerative condition with a two- to five-year life expectancy, and there is an urgent need for medications that can attack the degeneration process and slow the disease,” said James Wymer, M.D., a UF professor of neurology who led the UF arm of the clinical trial. “For the ALS community, the addition of another drug with efficacy gives our patients hope that we can impact this disease.”

At least 31,000 Americans are estimated to live with ALS, according to the Centers for Disease Control and Prevention.

The new drug, called AMX0035, showed promise in the 137-participant CENTAUR trial to slow the progression of ALS, which gradually limits the ability to move, speak, eat and breathe.

A subsequent analysis concluded that median survival was extended by 6½ months — from 18½ months in the group randomized to receive a placebo compared with 25 months for those randomized to receive treatment.

The phase 2, 25-site trial was led by Massachusetts General Hospital/Harvard Medical School, and the UF arm was conducted at the Norman Fixel Institute for Neurological Diseases at UF Health.

Fixel building
Norman Fixel Institute for Neurological Diseases at UF Health

The trial tested a combination of Buphenyl, or sodium phenylbutyrate, an FDA-approved drug to treat a rare genetic condition called urea cycle disorder, and the over-the-counter supplement taurursodiol. The combination, taken orally, was tested in a placebo-controlled, randomized, double-blind trial and found to slow the decline of day-to-day ability to function, according to results published in The New England Journal of Medicine.

The rate of decline was measured over six months using the Amyotrophic Lateral Sclerosis Functional Rating Scale Revised, or ALSFRS-R. The test is an assessment of fine motor, gross motor, breathing function and bulbar function, which includes speaking and swallowing.

The FDA approval followed two votes by its Peripheral and Central Nervous System Drugs Advisory Committee: first a vote of 6-4 to recommend against approval in March and then, following advocacy by ALS physicians, patients and families and additional analyses of the data, a vote of 7-2 in favor of approval earlier in September.

Doctor Michael Okun
Dr. Michael Okun

“Given the disagreement among experts on the FDA committee and ultimate approval of this drug, it becomes even more important that we spend sufficient quality time with patients and families as they make a decision whether to use this therapy,” said Michael S. Okun, M.D., executive director of the Norman Fixel Institute and chair of the UF department of neurology.

A phase 3 clinical trial designed to include 600 participants is now underway, including at UF, to continue to test the drug’s effectiveness.

Once the drug becomes available to the public, UF Health physicians will work with patients and families to discuss the risks and benefits and how to gain access.

“This approval by the FDA represents another milestone in developing a therapy that has proven benefit in the treatment of ALS,” Wymer said.

The research was funded by Amylyx Pharmaceuticals, Inc., maker of AMX0035; the ALS Finding a Cure Foundation; and the ALS Association.