The trial’s secondary endpoints assessed respiratory function and muscle strength, with no significant difference observed between the two cohorts. Credit: David Herraez Calzada / Shutterstock.

US-based biotechnology company Denali Therapeutics has reported that a Phase II/III trial of DNL343 for amyotrophic lateral sclerosis (ALS) failed to meet its primary endpoint.

The primary analysis included 186 subjects who received the therapy and 139 subjects who were given a placebo. The drug was investigated as part of the HEALEY ALS Platform trial.

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Its primary endpoints were to assess changes in disease severity over time using the ALS Functional Rating Scale-Revised, as well as survival rates up to week 24.

The trial’s secondary endpoints assessed respiratory function and muscle strength. These showed no significant difference between the therapy and placebo groups at the 24-week mark.

Denali reported that the therapy was safe and well-tolerated among subjects.

The company anticipates further analyses later this year, which will include neurofilament light (NfL) and other fluid biomarkers, as well as data from pre-specified subgroups and extended outcomes from the active treatment extension period.

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Denali Therapeutics chief medical officer Carole Ho said: “We are deeply grateful to the study participants, investigators, and the broader community for their collective support of the HEALEY study, which has provided an efficient and innovative platform for evaluating the therapeutic potential of DNL343 in addressing this critical unmet need.

“We look forward to a more comprehensive analysis of the study results as additional analyses, including pre-specified subgroup analyses and treatment effects on NfL, become available later in 2025.”

DNL343 is an investigational candidate operated by targeting eukaryotic initiation factor 2B (eIF2B), a key regulator of the integrated stress response.

This is considered a new small molecule therapeutic approach for treating ALS, an adult-onset progressive motor neuron disease.

The HEALEY ALS Platform Trial is a large-scale initiative designed to expedite the development of new ALS treatments by assessing several investigational therapies concurrently.

The study is being led by the Sean M Healey & AMG Center for ALS at Massachusetts General Hospital in collaboration with the Northeast ALS Consortium.