The manufacturer of the world’s newest treatment approved for amyotrophic lateral sclerosis (ALS), often called Lou Gehrig’s disease, has withdrawn the drug from the market because a large clinical trial did not produce evidence that the treatment worked.
It is also being sued by investors in a class action suit. The New York Times reports that the company, Amylyx Pharmaceuticals, has already started the process of withdrawing the drug in the US, where it is called Relyvrio, and in Canada, where it is called Albrioza.
As of Thursday last week, it said in a statement, no new patients would be able to start the drug, while current patients wanting to continue taking the medication can be transitioned to a free drug programme.
The medication is one of only a few treatments for the severe neurological disorder. When the US Food and Drug Administration approved it in September 2022, it concluded there was not yet sufficient evidence it could help patients live longer or slow the progression of the disease.
The agency decided to green-light the medication anyway, instead of waiting two years for results of a large clinical trial, citing data showing the treatment to be safe as well as the desperation of ALS patients. The disease robs patients of their ability to control muscles, speak and breathe without assistance, and often causes death in two to five years.
Since then, about 4 000 patients in the US have received the treatment, a powder that is mixed with water and either drunk or ingested through a feeding tube. Its listed price was $158 000 a year.
Last month, Amylyx said the results of a 48-week trial of 664 patients showed the treatment worked no better than a placebo, adding that it would consider pulling the drug from the market.
After the announcement last Thursday that it was pulling the plug on the drug, Justin Klee and Joshua Cohen, co-chief executive officers of Amylyx, said the company would continue to study the drug in two rare diseases, Wolfram syndrome and progressive supranuclear palsy.
This week, a law firm announced it had filed a class-action lawsuit against Amylyx on behalf of investors who purchased the company’s stock. The suit alleges Amylyx overstated the commercial prospects of Relyvrio, and did not disclose that patients were discontinuing the treatment after six months and that the rate of new prescriptions was decreasing.
The lawsuit also alleges that the company tried to hide the negative information from investors by preventing analysts from viewing data on prescriptions of Relyvrio.
Combination
Klee and Cohen conceived of Relyvrio about a decade ago as undergraduate students at Brown University. Their idea was that combining taurursodiol, a supplement sometimes used to regulate liver enzymes, and sodium phenylbutyrate, a medication for a paediatric urea disorder, could protect neurons in the brain from damage in diseases like ALS by preventing dysfunction of two structures in cells: mitochondria and the endoplasmic reticulum.
The FDA typically requires two persuasive clinical trials, usually phase 3 trials, which are larger and more extensive than phase 2 studies. For serious diseases with few treatments, the agency can accept one trial plus additional confirmatory data.
For Relyvrio, the data came only from one phase 2 trial in which 137 patients took either the drug or a placebo, plus an extension study that followed some patients after the trial ended when they were knowingly taking the drug.
The agency initially recommended that the company not apply for approval of the drug until the Phase 3 trial was completed in 2024. However, ALS advocacy groups campaigned vehemently to persuade the FDA to reconsider.
In March 2022, a committee of independent advisers to the FDA decided by a narrow margin that the treatment had not yet been shown to be effective, a conclusion also reached by the FDA’s own reviewers.
The agency then allowed Amylyx to submit more data and took the unusual step of scheduling a second independent advisory committee meeting in September 2022. In a report presented there, agency reviewers said they also considered the new data insufficient.
At that hearing, Dr Billy Dunn, then the director of the FDA’s office of neuroscience, asked the company whether, if the treatment received approval but later failed the phase 3 trial, it would voluntarily stop selling the medication.
Klee responded that if the trial “is not successful, we will do what is right for patients, which includes voluntarily removing the product from the market”.
That commitment, plus emotional testimony from patients and doctors, persuaded seven advisory committee members to favour approval, with only two opposing.
Later that month, the FDA granted the approval, writing that there was “residual uncertainty about the evidence of effectiveness”, but that “given the serious and life-threatening nature of ALS and the substantial unmet need, this level of uncertainty is acceptable in this instance”.
See more from MedicalBrief archives:
Large study shows ALS drug failures
Drug for Lou Gehrig’s gets regulatory nod despite questionable data
Concern from FDA committee about ALS cell therapy