AMX0035 Trial in Alzheimer Disease Doses First Patient


Amylyx Pharmaceuticals announced the trial of the 2-drug combination is seeking to enroll 100 patients with late-stage mild cognitive impairment or dementia due to Alzheimer, with plans to complete the study in 2020.

Dr Steven Arnold

Steven E. Arnold, MD, Translational Neurology Head of the Interdisciplinary Brain Center at Massachusetts General Hospital and Harvard Medical School

Steven E. Arnold, MD

The first patient was dosed in the phase 2 PEGASUS clinical trial to assess AMX0035, an investigational 2-drug combination treatment for Alzheimer disease developed by Amylyx Pharmaceuticals.

The company announced the dosing of the first of 20 enrolled patients in the recently expanded trial in conjunction with the Alzheimer’s Association, the Alzheimer’s Drug Discovery Foundation (ADDF) and the Cure Alzheimer’s Fund. The target enrollment is 100 patients.

AMX0035 is a combination of sodium phenylbutyrate and tauroursodeoxycholic acid, designed to reduce cell death originated in the mitochondria, a pathway which has recently been the subject of much more research in the Alzheimer field. It was developed using the rationale of successful tandem therapies in HIV/AIDS, cancer, and heart disease.

“The urgent need for a new approach to Alzheimer’s is clearer now than ever. As this is one of the first major combination therapy clinical trials for Alzheimer’s Disease, we’re optimistic about AMX0035’s potential to slow disease progression in individuals through its novel mechanisms of action,” Steven E. Arnold, MD, Translational Neurology Head of the Interdisciplinary Brain Center at Massachusetts General Hospital and Harvard Medical School, and the study’s principal investigator, said in a statement.

Rudolph Tanzi, PhD, of Massachusetts General Hospital, chair of the Cure Alzheimer’s Fund Research Leadership Group, and chair of the Amylyx SAB, noted that the “wealth of knowledge” gained from the numerous failed trials of therapies targeting amyloid and tau protein buildup has helped increase the knowledge of the disease. He added that the Cure Alzheimer’s Fund was “proud” to provide funding to a novel therapy.

PEGASUS was originally intending to enroll 50 patients, but the additional funding from the aforementioned organizations allowed for the target to double. The trial was originally supported through the ADDF and Alzheimer’s Association’s joint ACTO program. It is a double-blind, multicenter, placebo-controlled trial that will randomize patients with late-stage mild cognitive impairment or dementia due to Alzheimer in a 3:2 fashion for a 24-week period. PEGASUS is expected to read out results in 2020.

“There have been trials targeting amyloid, and there have been trials targeting tau, but this is the first trial to target 2 novel mechanisms in tandem,” Howard Fillit, MD, founding executive director and chief science officer of the ADDF, said. Fillit previously told NeurologyLive that the need for better clinical trials and novel medicines has never been more important. This is especially true for a biomarker focused trial such as PEGASUS.

“Today, we have a much better chance at having successful trials because we've learned how to do better trials with better drugs because we've been able to translate this basic research that we've done into drug discovery and development over this period of the last couple of decades,” he said.

“We believe AMX0035 has potential across multiple neurodegenerative diseases. We’re moving quickly to determine the synergistic efficacy of these 2 therapies and deeply value the support from the Alzheimer’s Drug Discovery Foundation (ADDF), the Alzheimer’s Association and the Cure Alzheimer’s Fund to expand this unique trial,” said Kent Leslie, Amylyx’s chief scientific officer.

AMX0035 is also being investigated in the treatment of amyotrophic lateral sclerosis (ALS), with a phase 2 clinical trial, CENTAUR (NCT03127514), currently enrolling patients. Its primary end points include the measure of decline in function according to the ALS functional rating scale, the incidence of adverse events, and the number of participants in each group who are able to remain on treatment until planned discontinuation.


Amylyx Pharmaceuticals Announces First Patients Dosed in PEGASUS Phase 2 Trial of AMX0035 in Alzheimer’s Disease and Expansion of the Trial [press release]: Cambridge, MA: Amylyx Pharmaceuticals; Published April 9, 2019. Accessed April 9, 2019.

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