Denali Therapeutics' Amyotrophic Lateral Sclerosis Misses Pivotal Trial, But Analyst Says It Was Expected

On Monday, Denali Therapeutics Inc. DNLI revealed topline results from an analysis of Regimen G of the Phase 2/3 HEALEY ALS Platform Trial evaluating DNL343 for amyotrophic lateral sclerosis.

Compared to placebo, the study did not meet the primary endpoint of efficacy in slowing disease progression.

The primary endpoint was evaluated as a change in disease severity over time as measured by the ALS Functional Rating Scale-Revised (ALSFRS-R) and survival through week 24.

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Key secondary endpoints, measuring muscle strength and respiratory function, were also not statistically different between the active and placebo groups at week 24.

For the primary analysis, 186 participants who were randomized to receive DNL343 treatment were compared to 139 participants randomized to receive placebo in this regimen (n=63) or shared from a concurrently enrolling regimen (n=76).

Overall, DNL343 was found to be safe and well-tolerated. Further analyses are anticipated later in 2025, including neurofilament light (NfL) and other fluid biomarkers, data from pre-specified subgroups, and extended findings from the active treatment extension period.

William Blair noted that while the update is disappointing for patients and investors, it isn’t entirely unexpected. This is due to the short treatment period and the complexity of the disease, which has a history of clinical trial challenges.

Biogen Inc. BIIB and Ionis Pharmaceuticals, Inc. IONS faced a similar situation with Qalsody, which failed to show significant improvement in ALSFRS-R scores over six months. However, it eventually received accelerated approval based on reduced NfL levels and indications of benefit with early treatment over 52 weeks.

Analyst Sarah Schram believes it’s too soon to abandon the program and is awaiting a more detailed analysis, expected in late 2025.

Price Action: DNLI stock is up 7.29% at $21.27 at the last check on Tuesday.

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