The Food and Drug Administration plans to convene a group of outside advisors to discuss an experimental and closely watched medicine developed by Biogen for the treatment of ALS.
The meeting of nervous system drug experts is scheduled for March 22, about a month before the FDA’s deadline for deciding whether to approve the medicine, called tofersen. The agency has, since last July, been reviewing tofersen, which Biogen submitted despite its failure in a key clinical trial.
Tofersen is designed to block the production of proteins created by SOD1 — a gene scientists believe gives rise to ALS, or amyotrophic lateral sclerosis, when mutated. While these mutations are present in only a small fraction of patients with the disease, SOD1 has remained a focal point of ALS research since it was first linked to the disease nearly three decades ago.
Biogen estimates that SOD1 ALS affects approximately 330 people in the U.S.
In that key trial, tofersen was shown to have an effect on its target. Among the patients who received the drug, SOD1 protein levels declined between 26% and 38% compared to the participants given a placebo.
Yet, the study still missed on its main goal of slowing the disease’s progression. After the results became available in late 2021, Biogen said it would engage with regulators and other stakeholders to figure out the next steps for its drug.
By mid-2022, the company had decided to pursue approval based on another finding from the trial: that tofersen-treated patients also experienced substantial reductions in a protein tied to neurological damage. Research indicates that when nerve cells get injured or die, levels of this “neurofilament light chain” protein become elevated in the blood or fluid around the brain and spine.
“In ALS in particular, the levels are quite high,” Toby Ferguson, head of the neuromuscular development unit at Biogen, said in an interview last year.
Biogen ultimately asked for what’s known as an accelerated approval, which hinges the effects a drug has on a biomarker “reasonably likely to predict clinical benefit.” The FDA agreed to review tofersen under this pathway, and initially expected to make a decision by Jan. 25. But the agency has since pushed back its deadline to late April, to give it more time to assess new information that it requested from Biogen.
Notably, the FDA has never before cleared a drug for market based on changes in neurofilament light chain levels.