Amylyx Plots New Path in Rare Genetic Disease After Relyvrio Withdrawal


Pictured: 3D illustration of a DNA double-helix/iStock,

Amylyx Pharmaceuticals on Thursday released interim results from its ongoing Phase II HELIOS trial, showing that its lead asset AMX0035 (sodium phenylbutyrate and taurursodiol) improved pancreatic function and glycemic control in adult patients with the rare, inherited neurodegenerative disease Wolfram syndrome.

The preliminary data, which come from eight participants who had completed 24 weeks of treatment, showed that AMX0035 treatment led to an increase in total C-peptide response, an established and objective laboratory marker of pancreatic beta cell function and glycemic control. Seven participants also saw at least a 30-minute decease in reaching peak C-peptide response.

According to the biotech, patients with Wolfram syndrome are expected to show “progressive decline” on this measure, particularly a longer time to reach peak C-peptide levels, which is indicative of poorer pancreatic response.

AMX0035 also met several other key endpoints in HELIOS, including HbA1c levels, which dropped by 0.26% on average after 24 weeks of treatment. Continuous glucose monitoring revealed that the absolute time in target range improved by 7.1% on average. All patients reached disease stability or improvement at week 24.

In terms of safety, AMX0035 was generally well tolerated and its adverse events were broadly in line with what had been established in prior studies. Most side effects were mild or moderate in severity, with no serious toxicities linked to the experimental drug.

“The improvements in C-peptide, an objective laboratory measure, observed in our HELIOS trial are promising and differ from the normal course of Wolfram syndrome despite best supportive care,” Amylyx CMO Camille Bedrosian said in a statement, adding that these data “support the compelling science behind the mechanism of action of AMX0035 and its potential to help people living with Wolfram syndrome.”

An inherited condition that typically includes childhood-onset insulin-dependent diabetes mellitus and progressive optic atrophy, many patients with Wolfram syndrome also develop diabetes insipidus, sensorineural hearing loss and autonomic nervous system degeneration.

AMX0035 is an orally available and fixed-dose combination of sodium phenylbutyrate and taurursodiol. The drug’s exact mechanism of action is not yet completely understood but it is believed to counter mitochondrial dysfunction and endoplasmic reticulum stress, boosting cellular function and curbing cell death.

Previously available commercially in the U.S. under the brand name Relyvrio, AMX0035  won the FDA’s approval in September 2022 for the treatment of amyotrophic lateral sclerosis. However, in March 2024, Relyvrio failed the Phase III PHOENIX trial missing its primary endpoint of ALSFRS-R total score change at 48 weeks. Relyvrio also failed key secondary endpoints such as slow vital capacity and self-reported health status.

Last week, Amylyx announced that it was voluntarily withdrawing Relyvrio from U.S. and Canadian markets. Patients currently on treatment will have the option to transition into a free program.

Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at or

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