The FDA’s Peripheral and Central Nervous System Drugs Advisory Committee (AdCom) voting against the new drug application of Amylyx’s AMX0035 for the treatment of amyotrophic lateral sclerosis (ALS) patients is extremely disappointing for the ALS community, but not entirely surprising, says GlobalData, a leading data and analytics company.

Sarah Elsayed, Neurology Analyst at GlobalData, comments: “Briefing documents released by the FDA prior to the AdCom meeting signaled concerns about the results of AMX0035’s Phase II CENTAUR study and the open label extension (OLE) CENTAUR-OLE study. GlobalData believes that even though this vote has narrowed AMX0035’s chances to get FDA approval by the target Prescription Drug User Fee Act date of June 2022, it has left the door open for AMX0035 to potentially present more robust data in the near future.”

AMX0035 is an orally administered combination of tauroursodeoxycholic acid (TUDCA) and sodium phenylbutyrate. Although AMX0035 met the primary endpoint of change in ALS Functional Rating Scale-Revised (ALSFRS-R) in the CENTAUR study, which enrolled 137 patients with ALS over a period of 24 weeks, questions remained over the modest benefits of the drug.

Elsayed continues: “AMX0035’s mechanism of action is seen as a promising addition to the treatment of ALS, which currently consists of just two modestly effective drugs: generic riluzole and Mitsubishi Tanabe Pharma’s Radicava (edaravone). The drug has a role in the downregulation of endoplasmic reticulum (ER) stress and mitochondrial dysfunction involved in ALS, thus reducing inflammation and neuronal cell death.

“Additionally, the drug is being regarded as safe and well-tolerated, supposedly because its two active constituents have been prescribed for a long time in other indications without serious side effects. In fact, key opinion leaders (KOLs) previously interviewed by GlobalData expressed concerns that some of their patients were already getting a hold of one of the drug’s constituents, TUDCA, which is available online as a dietary supplement.”

As such, KOLs noted that, given the huge unmet needs and the devastating nature of ALS, there is strong public pressure to get more drugs approved for this disease – despite AMX0035 showing modest benefits on survival and slowing disease progression. GlobalData expects that, if AMX0035 ultimately does get FDA approval, it will likely have a strong impact on the ALS market.

Elsayed adds: “With the FDA facing mounting scrutiny over its controversial approval of Biogen’s Aduhelm (aducanumab) for Alzheimer’s disease following an Adcom rejection, it is highly likely that Amylyx will need to address a number of concerns in the design of its new Phase III PHOENIX trial before it can reassure the regulatory authorities and gain approval. The topline results of the PHOENIX trial are expected to readout in H1 2024.”