Amyotrophic lateral sclerosis (ALS) gained new attention in the months following the FDA's approval of Mitsubishi Tanabe Pharma Corp.'s Radicava (edaravone). After three years of research, upstart Amylyx Pharmaceuticals Inc. seized that opening to move headlong into the field.

In collaboration with the ALS Association, ALS Finding a Cure and the Massachusetts General Hospital (MGH), Amylyx dosed the first patient in the phase II CENTAUR study assessing the efficacy and safety of AMX-0035 in patients with ALS.

AMX-0035 is an oral combination of two small molecules, sodium phenylbutyrate and tauroursodeoxycholic acid, that targets neuroinflammation and nerve cell death. Individually, each compound showed efficacy in cellular and animal models of ALS, explained Justin Klee, the company's co-founder and president. The agents also were tested individually in human ALS trials, where they showed preliminary signs of efficacy along with a good safety profile and were well-tolerated by patients.

In preclinical trials, Amylyx amassed data showing a synergistic effect between the two compounds, suggesting the combination might offer improved efficacy compared to the individual agents. The company's intellectual property is based on the proprietary combination, Klee said.

With just three full-time employees, Amylyx recruited the Neurological Clinical Research Institute at MGH and the Northeast ALS Consortium (NEALS) to oversee the trial, which will encompass 25 NEALS member medical centers across the U.S.

"We see ourselves as the experts in our drug and in our development," Klee told BioWorld. "But there's no way we're going to be an expert at running ALS clinical trials."

The double-blind trial is expected to enroll 132 participants with ALS who will be randomized across 24 weeks of treatment with AMX-0035 or placebo. The study is designed to assess safety and tolerability as well as impact on disease progression as measured by the revised Amyotrophic Lateral Sclerosis Functional Rating Scale, or ALSFRS-R, over the study period. Top-line data are expected in about two years.

CENTAUR will be first multicenter, interventional trial to evaluate the impact of AMX-0035 on isometric strength using the Accurate Test of Limb Isometric Strength, or ATLIS, technology. PET imaging of neuroinflammation and blood-based markers of neurodegeneration will be used to assess changes in disease pathology.

The company will offer an open-label extension for all enrolled patients following conclusion of the 24-week treatment period.

Funding for CENTAUR comes mainly from a $2.96 million grant from the ALS Association and ALS Finding A Cure, along with proceeds from a $5 million series A the Cambridge, Mass.-based company raised last year.

CENTAUR was designed with input from a range of clinical leaders in ALS, including Sabrina Paganoni, of MGH and Spaulding Rehabilitation Hospital, who serves as principal investigator, and Merit Cudkowicz, a renowned ALS researcher and chief of neurology at MGH. On the advice of clinicians, Amylyx also sought input from patients and caregivers, said Joshua Cohen, the company's co-founder and CEO.

"In clinical trial planning, often the patient's voice goes unheard," Cohen told BioWorld. The company recruited an ALS patient and a caregiver to serve as patient advocates, advising on the protocol and "to make the study as accessible as possible and to minimize the burden on participants. That's really important to us."

Amylyx – the name hints at amyloid, even though the drug is classified as a histone deacetylase inhibitor – plans to evaluate AMX-0035 in additional neurodegenerative diseases, potentially including Alzheimer's disease and Friedreich's ataxia, where the company is running preclinical validation and IND-enabling studies.

In ALS, which the co-founders called a "devastating" and "fast-progressing" disease where patients face new challenges every day, a key goal is to advance the field as well as the agent.

"We obviously designed the trial to see if AMX-0035 would be successful and fill a need in ALS," Cohen said. "But a second and equal focus of the trial is to push ALS forward, regardless of the outcome of the drug."

Ironically, the Amylyx trial was initiated the same day that Mitsubishi Tanabe placed its ALS drug, Radicava, on the U.S. market at a price tag of approximately $145,000 per year. Officials of the Osaka-based pharma confirmed on the company's quarterly earnings call on July 31 that the price received "no particular pushbacks" from payers.

In May, Radicava became the first drug in two decades to gain an FDA nod in ALS. The intravenously administered antioxidant free radical scavenger is being marketed in the U.S. through a newly formed subsidiary, MT Pharma America Inc., headquartered in Jersey City, N.J. (See BioWorld Today, May 9, 2017.)