On October 16, Amylyx announced that AMX0035, its amyotrophic lateral sclerosis (ALS) pipeline drug, showed potential to prolong patient survival and slow rapid disease progression in ALS patients. The results were published in the company’s open label extension (OLE) trial, which analyzed the overall survival of 90 ALS patients for up to 30 months following the main Phase II/III CENTAUR trial. The new functional and survival benefits of AMX0035 will significantly strengthen the drug’s position to enter the ALS market over the coming years as a potential disease-modifying therapy given its high tolerability profile and convenient oral administration.

AMX0035 is a combination of tauroursodeoxycholic acid (TUDCA) and sodium phenylbutyrate, which protects nerve cells from damage by targeting the endoplasmic reticulum and mitochondrial-dependent neuronal degeneration pathways in ALS patients. The pipeline drug’s safety, tolerability, and efficacy were assessed in the double-blind, placebo-controlled, Phase II/III CENTAUR clinical trial, which concluded in September 2019. Later, investigators demonstrated that AMX0035 slowed ALS disease progression over six months, with numerical benefits seen on secondary outcomes such as patients’ muscle strength, breathing, and frequency of hospitalizations. No serious adverse events were reported, so there were no modifications or interruptions of the study drug dosing.

Patients who completed CENTAUR were eligible to participate in an open-label extension study to evaluate the long-term safety and efficacy of AMX0035 over a period of 2.5 years. Survival analyses in this study compared time to death (all-cause mortality) between participants who had been originally randomized to AMX0035 and those who had been originally randomized to placebo, with the longest follow-up 35 months after randomization. Notably, there was a 44% risk reduction for death over the course of the follow-up period. Furthermore, AMX0035’s survival benefit was shown to be independent of baseline use of the standard of care drug, Sanofi’s Rilutek (riluzole), and/or Mitsubishi’s Radicava (edaravone), or both together. Key opinion leaders (KOLs) interviewed by GlobalData noted that if AMX0035 continued to show therapeutic benefits in trials, they would likely prescribe it to the majority of their patients upon approval, as it would address some major unmet needs and expand the existing treatment options in the ALS market.

The announced positive results support AMX0035’s clinical superiority and will advance its regulatory approval processes. This could encourage other companies to focus on developing pipeline agents with novel mechanisms of action that try to halt or slow the progression of the disease, rather than reformulating current ALS treatments.

Further opportunities could arise for another pipeline agent with a similar molecule. Bruschettini’s Tudcabil (TUDCA) is currently undergoing a multicenter Phase III trial in Europe to evaluate its safety and efficacy as an add-on treatment in ALS patients. GlobalData anticipates that Tudcabil will launch in 2022 in Europe, contributing $3.5M of sales to the global ALS market. By 2029, GlobalData forecasts the global ALS market to reach sales of $1.04B at a Compound Annual Growth Rate of 13.9%, driven by pipeline launches.

Despite the rarity of the disease, a high level of unmet need remains in the current treatment landscape, and there are still significant opportunities for pharmaceutical companies to address in this space, such as the need for a drug with curative and disease-modifying properties.