Denali Therapeutics’ ALS Drug DNL343 Fails to Meet Primary Efficacy Endpoints in Phase 2/3 HEALEY ALS Platform Trial

Clinical Trial Outcome:
Denali Therapeutics' Phase 2/3 HEALEY ALS Platform Trial for DNL343, an eIF2B agonist, failed to meet its primary endpoint of slowing disease progression compared to placebo over a 24-week period124.

Primary Endpoint:
The primary endpoint was the change in disease severity measured by the ALS Functional Rating Scale-Revised (ALSFRS-R) and survival rate through week 24124.

Secondary Endpoints:
Key secondary endpoints, including muscle strength and respiratory function, were also not statistically different between the active and placebo groups at week 24124.

Safety and Tolerability:
Despite the efficacy failure, DNL343 was found to be safe and well tolerated among participants124.

Future Analyses:
Additional analyses, including neurofilament light (NfL) and other fluid biomarkers, prespecified subgroup analyses, and extended findings from the active treatment extension period, are expected later in 2025124.

Market Impact:
The negative trial outcome is likely to trigger a substantial market reaction, potentially affecting Denali Therapeutics' market position and pipeline strategy4.

Sources:

1. https://www.globenewswire.com/news-release/2025/01/06/3005002/0/en/Denali-Therapeutics-Announces-Topline-Results-for-Regimen-G-Evaluating-eIF2B-Agonist-DNL343-in-the-Phase-2-3-HEALEY-ALS-Platform-Trial.html

2. https://www.investing.com/news/company-news/denali-reports-als-trial-misses-primary-goals-93CH-3798613

4. https://www.stocktitan.net/news/DNLI/denali-therapeutics-announces-topline-results-for-regimen-g-fsqa9snrzpp2.html