Upcoming ALS Treatments in Mid-Stage Trials

Recent advancements in the treatment of amyotrophic lateral sclerosis (ALS) have been overshadowed by setbacks in clinical trials. The approval of Relyvrio by Amylyx and Qalsody by Biogen and Ionis in the past two years had raised hopes, but Amylyx's withdrawal of Relyvrio following a failed Phase III trial and the disappointment of trials by Seelos Therapeutics, Sanofi, and Denali Therapeutics have dampened the mood.

The ALS research community, including Merit Cudkowicz from Massachusetts General Hospital, acknowledges a dearth in the number of significant trials. Analysts like Graig Suvannavejh from Mizuho Americas have noted a thinning of the pipeline. However, BrainStorm Cell Therapeutics is moving forward with a Phase IIIb trial for its cell therapy NurOwn after a Biologics License Application withdrawal, and Clene is set to initiate a Phase III trial for its CNM-Au8 gold nanocrystal suspension.

Despite a diminished late-stage pipeline, over 100 investigational treatments are in clinical development. Cudkowicz emphasizes the need for a deeper understanding of ALS biology to identify optimal targets. There is an ongoing effort to discover biomarkers to better stratify patients for improved clinical outcomes.

Five mid-stage therapies are currently under the spotlight:

Denali Therapeutics' DNL343: A small molecule activator of eIF2B, DNL343 is designed to inhibit cellular stress response and disease progression. It is well-tolerated and shows promise in inhibiting biomarkers associated with the stress response.

Calico Life Sciences' ABBV-CLS-7262: Developed in collaboration with AbbVie, ABBV-CLS-7262 is an eIF2B activator targeting the integrated stress response pathway. It is part of the Healey ALS Platform Trial, led by Cudkowicz, with enrollment complete and results expected later this year.

NeuroSense Therapeutics' PrimeC: A novel formulation combining ciprofloxacin and celecoxib, PrimeC is intended to regulate microRNA synthesis and reduce neuroinflammation. Early data suggests a positive trend in function and biomarker levels.

PTC Therapeutics' Utreloxastat (PTC857): This small molecule inhibits 15-lipoxygenase to reduce oxidative stress and aims to prevent glutathione depletion. It is currently in Phase II trials with results expected in late 2024.

Coya Therapeutics' COYA 302: A regulatory T cell-targeted therapy, COYA 302 combines low-dose interleukin-2 and CTLA-4 Ig to enhance anti-inflammatory functions. It has shown good tolerability in a proof-of-concept study.

While the path forward is not without challenges, these therapies represent the ongoing efforts to combat ALS and improve patient outcomes.