Amylyx Pharmaceuticals doses first patient in phase II clinical trial of AMX0035

The Neurological Clinical Research Institute (NCRI) at the Massachusetts General Hospital (MGH) and the Northeast ALS Consortium (NEALS) will oversee the trial, and 25 NEALS member medical centers across the United States will participate.

CENTAUR (“Combination of Phenylbutyrate and Tauroursodeoxycholic Acid”), which will enroll 132 participants nationwide, was designed in collaboration with patients and caregivers along with clinical leaders in ALS.

The design is intended to facilitate trial access, ease of trial site visits, patient engagement, and to measure both functional and biochemical changes over time. Amylyx plans to provide an open label extension to people who participate in CENTAUR.

“The CENTAUR trial builds on promising results with AMX0035 in preclinical studies and clinical experience with the drug’s two components,” said Sabrina Paganoni, M.D., Ph.D., Principal Investigator for the study and physician at the Massachusetts General Hospital and Spaulding Rehabilitation Hospital.

“The team at NCRI worked closely with Amylyx to design an innovative trial that will evaluate AMX0035’s safety and efficacy, advance our understanding of several biomarkers, and provide insights into ALS disease biology.”

Merit Cudkowicz, M.D. MSc, Chief of Neurology at MGH, added, “The design and launch of the CENTAUR trial reflects a close collaboration between academia, industry, ALS organizations, and patients. Collaborative efforts among key stakeholders is essential to developing treatments for this complex and serious disease.”

The study will be the first multi-center, interventional trial to utilize ATLIS™ (“Accurate Test of Limb Isometric Strength”), a novel technology developed by Pat Andres, DPT, to quantitatively assess changes in patients’ muscle strength.

PET imaging of neuroinflammation and blood-based markers of neurodegeneration will also be utilized to assess changes in disease pathology. Support for CENTAUR comes in part from a $2.96 million grant from The ALS Association and ALS Finding A Cure®.

Amylyx CEO and co-founder, Joshua Cohen commented, “We are tremendously grateful for the support we have received from the ALS community.” Justin Klee, President and co-founder added, “The study reflects the outstanding progress the Amylyx team and our collaborators made to build a strong clinical program aimed at ultimately improving the lives of patients with this devastating disease.”

The Amylyx therapeutic candidate, AMX0035, is an oral combination of sodium phenylbutyrate (PB) and tauroursodeoxycholic acid (TUDCA) that works synergistically to reduce neuronal death and inflammation.

Both PB and TUDCA have been individually tested in previous ALS clinical trials; both compounds demonstrated safety, tolerability, and preliminary signs of efficacy.

CENTAUR is a 24-week, randomized, double-blind, placebo-controlled Phase II clinical trial in 132 participants with ALS. The trial’s primary objectives are to evaluate the safety and tolerability of AMX0035 and assess the drug’s impact on disease progression as measured by the revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) over the 24-week study period.

The trial will also evaluate the impact of AMX0035 on isometric strength as measured by ATLIS, respiratory function, and exploratory biomarkers. There will also be an open label extension to the trial so that all enrolled patients will have the option of continuing treatment once the 24-week treatment period concludes.

AMX0035 is an oral combination of two small molecules, sodium phenylbutyrate (PB) and tauroursodeoxycholic acid (TUDCA). Each compound has demonstrated strong efficacy in several cellular and animal models of ALS. When individually tested in ALS clinical trials, PB and TUDCA have both shown safety, tolerability, and preliminary signs of efficacy.

In preclinical trials, Amylyx has demonstrated a synergistic effect between the two compounds, suggesting that the combination may have improved efficacy compared to the individual agents.

Amyotrophic lateral sclerosis, ALS, is the most prevalent adult-onset progressive motor neuron disease, affecting approximately 30,000 people in the U.S. and an estimated 450,000 people worldwide.

ALS causes the progressive degeneration of motor neurons, resulting in rapidly progressing muscle weakness and atrophy that eventually leads to partial or total paralysis; on average, the disease is fatal within just four years. There are currently just two therapies approved specifically for treating ALS—riluzole and the recently-approved edaravone.