Amylyx's New Approach in Genetic Disease Post-Relyvrio

Amylyx Pharmaceuticals has recently shared interim findings from its Phase II HELIOS clinical trial, which is currently underway. The study focuses on the effects of AMX0035, a compound consisting of sodium phenylbutyrate and taurursodiol, on adults suffering from Wolfram syndrome, a rare genetic disorder characterized by neurodegeneration.
The initial results, based on eight participants who completed a 24-week treatment regimen, indicated that AMX0035 significantly enhanced pancreatic function and blood sugar management. Specifically, the treatment led to a notable rise in the total C-peptide response, a recognized indicator of the functionality of pancreatic beta cells and the body's ability to regulate glucose levels. Among the participants, seven experienced a reduction of at least 30 minutes in the time taken to reach the peak C-peptide response, which is typically associated with a decline in pancreatic health in patients with Wolfram syndrome.
In addition to the C-peptide improvements, AMX0035 achieved other critical benchmarks in the HELIOS trial. HbA1c levels, a measure of blood sugar control, dropped by an average of 0.26% after 24 weeks of treatment. Continuous glucose monitoring showed an average increase of 7.1% in the time spent within the target blood sugar range. By the end of the trial period, all participants demonstrated either stabilization or improvement in their disease status.
Safety-wise, AMX0035 was found to be generally well-tolerated, with adverse effects aligning with previous research findings. The majority of side effects were categorized as mild or moderate, and no severe toxicities were attributed to the drug.
Amylyx's Chief Medical Officer, Camille Bedrosian, expressed optimism about the trial's findings, stating that the observed improvements in C-peptide levels are encouraging and deviate from the typical progression of Wolfram syndrome, even with the best supportive care. She also emphasized that the data reinforce the scientific rationale behind AMX0035's mechanism of action and its potential to assist individuals living with the syndrome.
Wolfram syndrome is an inherited condition that often includes insulin-dependent diabetes during childhood and progressive vision loss. Affected individuals may also experience additional symptoms such as excessive thirst and urination, hearing impairment, and degeneration of the autonomic nervous system.
AMX0035 is an orally administered combination therapy whose precise mode of action is still under investigation. However, it is hypothesized to mitigate issues related to mitochondrial dysfunction and endoplasmic reticulum stress, thereby enhancing cellular health and reducing cell death.
Previously marketed in the U.S. as Relyvrio, AMX0035 received FDA approval in September 2022 for the treatment of amyotrophic lateral sclerosis (ALS). However, in March 2024, Relyvrio did not meet its primary endpoint in the Phase III PHOENIX trial, which assessed changes in the ALS Functional Rating Scale-Revised (ALSFRS-R) score after 48 weeks. The drug also failed to achieve key secondary endpoints related to lung function and self-reported health status.
In light of these results, Amylyx has decided to voluntarily withdraw Relyvrio from the U.S. and Canadian markets. Current patients have the option to transition to a complimentary program.