ALS patient treated with TRE-515 in expanded access program
The patient had received more than 10 different treatments, without success
A patient with late-stage amyotrophic lateral sclerosis (ALS) was treated with TRE-515, Trethera’s investigational therapy, under a U.S. Food and Drug Administration (FDA) expanded access program, the company has announced.
The program enables patients with life-threatening conditions, including ALS, to receive experimental therapies outside clinical trials when no satisfactory alternatives exist. When they are integrated into a therapy’s development process, expanded access trials offer several benefits, including broader patient engagement, identifying potential biomarkers to predict treatment response, and data to inform and refine future clinical trials.
The expanded access program for ALS is being developed in collaboration with the Cedars-Sinai Medical Center in Los Angeles and Providence Saint John’s Health Center in Santa Monica, also in California.
“This trial marks a significant milestone as the first clinical use of TRE-515 beyond cancer,” Ken Schultz, MD, CEO of Trethera, said in a company press release. “Our approach has the potential to extend survival and improve quality of life for patients facing this devastating neurodegenerative disease.”
ALS features the progressive dysfunction and loss of motor neurons, the specialized nerve cells that control muscle movement. Its exact causes are unknown, but it’s thought that neuroinflammation is a contributing factor to the disease’s progression.
A ‘significant milestone’
TRE-515 is an oral medication under development for autoimmune diseases and in clinical trials for solid tumors. It’s a small molecule inhibitor of deoxycytidine kinase, a key enzyme in the salvage pathway, which is implicated in the abnormal and rapid cell growth associated with cancer, along with certain autoimmune and inflammatory conditions.
“FDA-approved options to treat ALS are severely limited. Exploring alternatives with first-in-class drugs for patients lacking available therapies represents the continued advancement of science,” said Frank Diaz, MD, PhD, a professor of neurology at Cedars-Sinai.
The patient, diagnosed with ALS in May 2022, had received more than 10 different treatments, including riluzole (sold as Tiglutik and available as generics), without success. In the four months before starting TRE-515, the patient’s forced vital capacity (FVC), a measure of lung function, decreased from 60% to 37%, despite several treatments and stem cell therapy.
During three months of treatment with TRE-515, the patient’s FVC and functional status, assessed by the Revised ALS Functional Rating Scale (ALSFRS-R), stabilized and he reported a gain in body weight, along with improvements in neck tone and arm strength. No adverse events were observed.
Based on these observations, the multicenter medical review group voted unanimously to increase the dose of TRE-515 and extend the study.
“We are particularly excited about the potential for TRE-515 as an ALS treatment given its ability to selectively modulate inflammation and its favorable safety profile,” said Daniel Kelly, MD, president of the Pacific Neuroscience Institute Foundation at Saint John’s Health Center. “We look forward to continued development of this promising therapeutic candidate for patients in need of therapies that improve the course of disease.”
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