Patient organisations have been celebrating the FDA approval yesterday of Amylyx’ amyotrophic lateral sclerosis (ALS) therapy Relyvrio, after not one but two advisory committee meetings that arrived at different conclusions about the drug.
The approval makes Relyvrio (sodium phenylbutyrate and taurursodiol) the first new therapy option for ALS – also known as motor neuron disease (MND) – since Mitsubishi Tanabe Pharma’s intravenous Radicava (edaravone) was cleared by the FDA in 2017. An oral version of edaravone was cleared this year.
Relyvrio takes the form of a powder that is mixed with water and can be taken via a feeding tube, and has been approved based on the phase 2 CENTAUR trial in patients with fast-progressing ALS, which showed a 25% slower decline in physical abilities like walking, speaking and swallowing than participants given a placebo.
An open-label extension revealed that ALS patients had around six more months before being hospitalised, requiring a ventilator or dying compared to the control group, and according to Amylyx patients who continued taking the drug survived about 10 months longer.
In March, the first advisory committee agreed with the opinion voiced by the FDA reviewer that there were doubts about the efficacy of Relyvrio, and that it would be preferable to wait for the results of an ongoing, larger study – now expected to read out in 2024.
That six-to-four vote not to recommend approval was followed by an outcry from ALS patient groups, which argued strongly that it would be better for patients with limited lifespan to take a chance on a new drug that appears to be safe, even though it may be found ineffective down the line.
The alternative – to hold back a therapy that proved itself later on – would mean some patients will have been denied the chance to delay disability progression and death, they contended.
Faced with the backlash, the FDA took the highly unusual step of convening another advisory committee meeting earlier this month, and amid emotional pleas from patients and doctors this time the vote went the other way by a seven-to-two margin.
The FDA clearly still has reservations about Relyvrio, saying in a summary memorandum published yesterday that there is “a degree of residual uncertainty about the evidence of effectiveness.”
However, it added that the limited efficacy of the two approved therapies for ALS – Radicava and oral riluzole – plus the apparent safety of Relyvrio means that “this level of uncertainty is acceptable in this instance and consideration of these results in the context of regulatory flexibility is appropriate.”
The ALS Association greeted the decision with joy, calling it an “amazing development in the fight against ALS.”
(1/2) BREAKING NEWS: @US_FDA approved AMX0035, a new treatment that has been shown to slow progression of #ALS and extend life. This is an amazing development in the fight against ALS, and a meaningful win for the entire ALS community who worked tirelessly to make this happen. pic.twitter.com/Kck0tp1nSJ
— The ALS Association (@alsassociation) September 29, 2022
The organisation contributed $2.2 million to the development and study of Relyvrio, using money raised through the 2014 Ice Bucket Challenge.
Meanwhile, Relyvrio has already been conditionally approved in Canada under the Albrioza brand name, although it has not yet launched there as Amylyx remains in pricing negotiations. There is also no word yet on pricing plans in the US, although they may be revealed at an investor update later today.
“Our priority now is to ensure that adults living with ALS in the US whose doctors have prescribed Relyvrio can access it as quickly as possible,” said Amylyx chief commercial officer Margaret Olinger.
“Physicians will be able to prescribe immediately, and we anticipate specialty pharmacies will be able to start to fill prescriptions and ship Relyvrio to people with ALS in the next four to six weeks.”
In both the US and Canada, staying on the market will depend on the outcome of the 600-patient PHOENIX study in two years. The drug was also filed for approval in Europe in February, with a decision due in early 2023.
Bad news for Biohaven
There was disappointing this week for another ALS drug developer this week however, after Biohaven revealed that its oral myeloperoxidase (MPO) inhibitor verdiperstat failed to slow progression of the disease in the phase 2/3 HEALEY ALS Platform trial.
The adaptive study, run by clinicians at Massachusetts General Hospital, is testing a basket of several drug candidates to try to find preliminary evidence of efficacy. Verdiperstat also failed a phase 3 trial in multiple system atrophy last year.
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