Nearly a week after pulling Relyvrio, Amylyx to engage regulators about the drug's path in another rare disease

On the heels of Relyvrio’s market withdrawal in amyotrophic lateral sclerosis (ALS), Amylyx Pharmaceuticals has shared early data from a phase 2 trial in a separate rare disease that the biotech is touting as “clinically meaningful.”

The interim data come from an ongoing midstage trial, dubbed HELIOS, among adults with Wolfram syndrome, a rare genetic disease that impacts about 3,000 Americans. Patients with the autosomal recessive neurodegenerative condition have a poor prognosis, facing the possibility of severe neurological disability and premature death.

Amylyx believes AMX0035, a fixed-dose combination of sodium phenylbutyrate and taurursodiol, could slow neurodegeneration by targeting endoplasmic reticulum stress and mitochondrial dysfunction. The company is testing the investigational oral treatment among 12 patients in an open-label study measuring two primary endpoints: the drug’s efficacy and its safety and tolerability profile. 

The primary efficacy endpoint measures change from baseline in C-peptide, an established lab measure of pancreatic beta cell function and glycemic control. Early data from eight participants who have completed 24 weeks of treatment found average increases in total C-peptide responses at Week 24.

For patients with Wolfram syndrome, a progressive decline would be expected on this measure without any treatment, Amylyx said in the April 10 release.

Meanwhile, AMX0035’s safety profile was consistent with earlier safety data, and the drug was found to be generally well tolerated, according to Amylyx. Most adverse events were mild or moderate, with no serious side effects related to AMX0035 treatment occurring.

The data demonstrated that AMX0035 had a “clinically meaningful effect” on key outcomes, such as the progression of diabetes, visual decline and overall disease burden, according to Amylyx. Figures regarding statistical significance were not shared.

When asked, a company spokesperson told Fierce Biotech "these findings are statistically significant," in an emailed statement. 

"Since these data represent an interim analysis, we believe it is not appropriate to include a p-value," the Amylyx spokesperson said.

"Outcomes for people with Wolfram syndrome consistently worsen over time, so disease stabilization alone is clinically meaningful for both patients and their doctors," Fumihiko Urano, M.D., Ph.D., principal investigator of the HELIOS trial and professor at Washington University School of Medicine in St. Louis, said in the April 10 release. "The interim results from HELIOS that demonstrate improvement across multiple organ systems impacted by this progressive disease are encouraging."

Investors didn't appear to share the optimism. After the data were shared at market open April 10, the company's share price fell by around 6% as of 3 p.m. ET.

Amylyx intends to meet with regulatory authorities to discuss a development path for AMX0035 in Wolfram syndrome, Amylyx co-CEO Joshua Cohen said on an April 10 company call. A top-line data readout from HELIOS is slated for the second half of this year, he said.

In a February interview with Fierce Pharma, co-CEO Justin Klee said because Wolfram is an ultra-rare disease, the company may pursue a different regulatory path than it did in ALS. HELIOS is the first interventional study in the indication, Klee noted.  

Back in 2020, the FDA granted AMX0035 orphan-drug designation for Wolfram syndrome, a status given to certain investigational drugs that hold therapeutic potential in a rare disease.

The data drop comes less than a week after the company pulled AMX0035, approved as Relyvrio to treat ALS, from the market after the drug failed in a confirmatory trial. In the phase 3 study, Relyvrio didn’t beat placebo at improving patients’ physical function on the revised ALS functional rating scale, a key measurement of clinical benefit.

The failed trial and market withdrawal are serious setbacks in the ALS field, where there are few options to treat the fatal neurodegenerative disease.

Relyvrio had served as Amylyx’s sole source of revenue, so the withdrawal prompted the Massachusetts biotech to lay off about 70% of its workforce. The company employs around 100 staffers after the cuts. 

The biotech is also testing AMX0035 in a phase 3 trial in progressive supranuclear palsy, with a readout now expected around mid-2025.

Editor's note: This article was updated at 9:45 a.m. ET to include comment from Amylyx.