Denali Therapeutics Faces Another Setback in ALS Treatment Development

Denali Therapeutics' DNL343 Fails in Phase II/III Trial:
The HEALEY ALS Platform trial of DNL343, an investigational candidate for amyotrophic lateral sclerosis (ALS), failed to meet its primary endpoint, which was to assess changes in disease severity over time using the ALS Functional Rating Scale-Revised and survival rates up to week 2425.

Previous Failure with SAR443820:
This is not the first failure for Denali in ALS treatment development. In February 2024, Denali's oral therapy candidate SAR443820 (DNL788) also failed to slow ALS progression in a Phase 2 clinical trial, missing its primary goal1.

HEALEY ALS Platform Trial Challenges:
The HEALEY ALS Platform trial has experienced challenges, including failures from other companies such as Seelos Therapeutics, which filed for bankruptcy after its candidate trehalose failed in the trial3.

Future Plans:
Denali plans to conduct further analyses later in 2025, including neurofilament light (NfL) and other fluid biomarkers, as well as data from pre-specified subgroups and extended outcomes from the active treatment extension period5.

ALS Treatment Landscape:
The ALS treatment landscape remains challenging, with few effective treatments available. The HEALEY ALS Platform trial aims to expedite the development of new ALS treatments by assessing several investigational therapies concurrently35.

Sources:

1. https://alsnewstoday.com/news/denali-therapy-candidate-fails-slowing-als-progression-trial/

2. https://www.thepharmaletter.com/pharmaceutical/denali-suffers-als-drug-failure-in-phase-iiiii-trial

3. https://www.biospace.com/drug-development/healey-als-trial-serves-up-more-disappointment-as-denali-abbvie-calico-fail

5. https://www.clinicaltrialsarena.com/news/denali-als-trial-fails-endpoint/