Investigational compound EPI-589 was found to be safe and well-tolerated, improved biomarkers of neuroinflammation, and showed signs of slowing disease progression in amyotrophic lateral sclerosis (ALS) patients, according to a completed Phase 2a clinical trial.
BioElectron Technology Corporation’s EPI-589, or (R)-troloxamide quinone, is a 250 mg immediate-release, film-coated tablet designed to be taken orally. It targets oxidoreductase enzymes, responsible for transferring electrons between molecules and critical in energy regulation, inflammation, and “programmed” cell death — as opposed to cell death caused by injury.
Besides ALS, the therapy candidate is being developed for neurodegenerative diseases characterized by inflammation, including Parkinson’s disease.
The open-label Phase 2a trial (NCT02460679) assessed the compound’s safety, tolerability, and pharmacological profile in 21 ALS patients between the ages of 21 and 70 who had already been taking Sanofi’s Rilutek (riluzole) and/or dietary supplements for at least 30 days.
Trial goals also included finding central nervous system and blood biomarkers consistent with ALS, therapeutic targets, and a mechanism of action. For this purpose, the participants underwent a 30-day run-in period to determine baseline biomarker and clinical status. They then took EPI-589 for 90 days, after which they were followed for an additional three months.
The study achieved its primary goal, with no therapy-related serious adverse events or dose-limiting toxicities within the six months.
Treatment with EPI-589 also led to a statistically significant improvement in cerebrospinal fluid — a liquid found in the brain and spinal cord — and plasma-based biomarkers known to correlate with neuroinflammation and ALS disease progression.
Clinical assessments further suggested that EPI-589 may slow disease progression, as assessed by the ALS Functional Rating Scale-Revised, and improve patients’ grip strength and swallowing.
“These data demonstrating drug safety, tolerability, and disease biomarker effect all provide a strong rationale for the continued development of EPI-589 for ALS,” Matthew Klein, BioElectron’s CEO, said in a press release. Klein also said that the effect on biomarkers of neuroinflammation and disease progression “support the development of EPI-589 for other neurological disorders characterized by neuroinflammation.”
The trial was conducted at three leading ALS centers in the U.S.: California Pacific Medical Center (CPMC) in San Francisco, Cedars-Sinai Medical Center in Los Angeles, and Providence Portland Medical Center in Portland, Oregon.
“The results of this trial are very encouraging for the ALS community,” said Robert Miller, MD, the study’s principal investigator and director of the Forbes Norris ALS/MDA Research and Treatment Center at CPMC. “A safe and effective orally administered medication would be a significant addition to the treatment of ALS patients.”
Trial results will be presented at the 29th International Symposium on ALS and Motor Neuron Disease, taking place Dec. 7-9 in Glasgow, Scotland.
BioElectron, formerly known as Edison Pharmaceuticals, is now planning a longer, placebo-controlled trial to establish clinical benefits.
EPI-589 is being developed in collaboration with Sumitomo Dainippon Pharma, which holds licensing rights for the compound in Japan and North America. It is BioElectron’s second compound in clinical development after EPI-743, which targets mitochondrial disease and related disorders.