Shares in Amylyx Pharma slid today after the FDA published a less-than-enthusiastic assessment of its amyotrophic lateral sclerosis (ALS) therapy ahead of an advisory committee meeting on Wednesday.
The document indicates that while data from Amylyx’ CENTAUR trial of AMX0035 is “encouraging”, the FDA reviewer believes a another randomised, placebo-controlled study “would likely be necessary to support a marketing application.”
The assessment comes just a few months after Amylyx opted to file for approval of AMX0035 (sodium phenylbutyrate and taurursodiol), despite telling investors earlier that it would probably have to complete another trial beforehand.
The change of approach came after what it described as favourable discussions with the FDA at a pre-NDA meeting in July, and the briefing document notes that the FDA talked to the company about its ability to submit the application quickly “to allow for earlier review of the data.”
CENTAUR met its main efficacy objective of slowing ALS as measured by the ALS Functional Rating Scale-Revised (ALSFRS-R), showing that after three years patients treated with AMX0035 were 44% less likely to die than those taking placebo, with a median survival of 25 months versus 18.5 months.
The FDA has concerns that despite the top-line improvement in survival, the results may be hard to interpret because of a large number of dropouts from the study and the way the rating scale data was analysed.
However, the agency also acknowledges that ALS has few effective treatments and so there may be room for “regulatory flexibility” – setting up what looks likely to be a lively debate at the advisory committee.
There is a handful of approved drugs on the market that try to slow down the progression of ALS, notably various oral formulations of riluzole and Mitsubishi Tanabe’s intravenous Radicava (edaravone) which was approved in 2017.
Investors in Amylyx showed their disappointment at the stance taken by the reviewer, and shares in Amylyx were down around 48% at the time of writing.
In ALS, which is also known as motor neurone disease, the nerve cells that control muscle function slowly die off. The two active ingredients in AMX0035 are thought to reduce neuronal death by regulating mitochondrial and endoplasmic reticulum pathways in nerve cells.
AMX0035 has already been submitted for approval in Europe and Canada, so the proceedings of the advisory committee meeting could be a forerunner of regulatory deliberations outside the US as well.
After its initial recommendation that Amylyx run an additional trial, the FDA came in for criticism from the ALS Association, which urged the regulator to come into alignment with Canada and Europe in allowing the drug to be filed for conditional approval while the biotech completes an ongoing PHOENIX phase 3 study.
The results of that study are due in 2024, so Amylyx could face a fairly lengthy delay if the FDA advisors press for that data prior to approval.
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