The Food and Drug Administration will meet Wednesday to consider approval of an experimental treatment for Lou Gehrig’s disease, the culmination of a yearslong lobbying effort by patients with the fatal neurodegenerative disease.

Those advocates still face one giant hurdle: FDA regulators say the treatment hasn’t been shown to work.

In documents posted Monday, the FDA reiterated its long-standing position that a lone study by drugmaker Brainstorm doesn’t provide convincing evidence that its stem cell-based therapy helps patients with ALS, or amyotrophic lateral sclerosis.

It’s the same message the FDA delivered to company executives in early 2021 when they first shared data on the treatment, dubbed Nurown. And again last November, when the FDA refused to accept the company’s application for review.

But with the backing of thousands of ALS patients, Brainstorm took the rare step of “filing over protest,” essentially forcing the agency to render a decision.

“FDA is the 800-pound gorilla here and if they’re convinced that the drug doesn’t work it’s very hard to change their minds,” said Marc Scheineson, a former associate FDA commissioner who now consults for drugmakers.

In the documents posted Monday, FDA reviewers outlined their “major concerns” about the company’s evidence.

Still, ALS patients see reasons for optimism. Under pressure from the ALS community and Congress, FDA officials have recently emphasized the “urgent need” for new ALS treatments and pledged to use maximum “regulatory flexibility” when reviewing them. FDA has approved two new ALS drugs in the last year, neither of which met the agency’s traditional approval standards.