Innovative Alzheimer’s Combination Therapy Trial Supported by New Joint Funding Initiative

The Alzheimer’s Drug Discovery Foundation (ADDF) and the Alzheimer’s Association are collaborating to jointly fund a new combination therapy clinical trial for Alzheimer’s disease to be conducted by Amylyx Pharmaceuticals. The $1.85 million grant is the first award under an initiative created by the ADDF and the Alzheimer’s Association to fund combination therapies.

The grant will support a phase 2 clinical trial of AMX0035, a combination of sodium phenylbutyrate (PB) and tauroursodeoxycholic-acid (TUDCA). The trial, expected to begin in the first half of 2018, will include approximately 50 people with mild cognitive impairment or mild-to-moderate Alzheimer’s disease and test the drug’s effectiveness at slowing or stopping brain cell death.

“Combination therapies hold great potential to slow the progression of Alzheimer’s,” said Howard Fillit, MD, the ADDF’s founding executive director and chief science officer. “The innovation of Amylyx’s combination therapy is that it targets multiple causes of brain cell loss, and the two drugs given in tandem create additional protective effects. The ADDF was an early supporter of innovative targets for Alzheimer’s, and we believe combination therapies are a critical next step in finding effective treatments for the disease.”

Alzheimer’s is a complex disease with multiple, interrelated causes. A growing number of experts believe combination therapy—with two or more drugs, or drugs and lifestyle interventions—will be required to effectively treat it.

“We have witnessed the success of combination therapy in HIV/AIDS, cancer, and heart disease. There is strong reason to believe that to successfully address Alzheimer’s, and its extraordinary complexity, we need to attack the disease on multiple fronts,” said Maria Carrillo, PhD, Alzheimer’s Association chief science officer. “Meetings convened in 2015 by the Alzheimer's Association (proceedings published in 2016) and the ADDF led the two organizations to recognize the potentially important role of combination therapies in Alzheimer’s and paved the way for this exciting partnership and initial clinical trial funding.”

New approaches to Alzheimer’s are urgently needed, as deaths from the disease continue to rise precipitously as more and more Baby Boomers reach the age of greatest risk.

The grant was made through the Alzheimer’s Combination Therapy Opportunities (ACTO) program, a joint research funding initiative created by the ADDF and the Alzheimer’s Association to support clinical trials combining multiple treatment approaches. The ACTO program specifically called for study proposals using repurposed drugs that have been determined safe for use in treating other conditions. Repurposing may speed the drug development process because researchers can often begin with Phase 2 trials including outcome measures of effectiveness, rather than phase 1 safety tests.

The drug to be tested, AMX0035, is a proprietary oral formulation of two existing therapeutics. PB is an FDA-approved therapy—currently prescribed for urea-cycle disorders—that activates genes responsible for protecting brain cells from toxic unfolded proteins. TUDCA is an acid produced in small amounts by the body that targets cellular energy loss. In preclinical studies conducted by the company and with academic collaborators, combination dosing of PB and TUDCA protected brain cells from inflammation and oxidation. Amylyx received FDA clearance for AMX0035’s Investigational New Drug application in April 2017 and has an ongoing multicenter clinical study of the compound in people with amyotrophic lateral sclerosis (ALS).

“We are very grateful for the support from the Alzheimer's Association and the Alzheimer's Drug Discovery Foundation, and we’re honored to partner with them in this new combination therapy initiative,” said Kent Leslie, Amylyx chief scientific officer. “Through a combination approach targeting two different and independent pathways, AMX0035 is designed to benefit both neurodegeneration and neuroinflammation, key drivers of Alzheimer's and ALS. The biomarker-focused trial design will assist in translating the promising preclinical effects observed in models of Alzheimer’s to an improved understanding of the potential of AMX0035 to help individuals living with this disease.”