Upcoming ALS Therapies: 5 Promising Mid-Stage Candidates

Recent advancements in the treatment of amyotrophic lateral sclerosis (ALS) have experienced a setback following the withdrawal of Amylyx’s Relyvrio from the market due to an unsuccessful Phase III trial. This comes after the drug was approved in 2022, marking a significant step forward in ALS treatment. Additionally, Biogen and Ionis’ Qalsody received approval in 2023, but the recent failures have led to a pause in progress.

Despite the challenges, there are over 100 experimental treatments in various stages of clinical development. The focus now is on a deeper understanding of the disease's biology to identify the most effective targets. A key aspect of this is the discovery of biomarkers to enhance the stratification of patients and improve clinical outcomes.

Several mid-stage therapies are being closely watched in the ALS research community:

Denali Therapeutics’ DNL343: This is a small molecule activator of eIF2B, designed to inhibit the cellular stress response and slow disease progression. It is currently in a Phase IIb/III trial, with the aim of enrolling patients by 2024.

Calico Life Sciences’ ABBV-CLS-7262: Developed in partnership with AbbVie, this eIF2B activator targets the integrated stress response pathway. It is being evaluated in the Healey ALS Platform Trial, with an expected completion in October of this year.

NeuroSense Therapeutics’ PrimeC: This novel formulation combines ciprofloxacin and celecoxib to regulate microRNA synthesis and reduce neuroinflammation. The Phase IIb PARADIGM trial results are promising, showing a slowing of disease progression.

PTC Therapeutics’ Utreloxastat: This small molecule inhibits 15-lipoxygenase to reduce oxidative stress and aims to prevent the depletion of glutathione. It is currently in the Phase II CardinALS trial, with results expected by the end of 2024.

Coya Therapeutics’ COYA 302: A regulatory T cell-targeted therapy, COYA 302 is in Phase II trials for ALS. It is a biologic combination therapy with a dual immunomodulatory mechanism designed to enhance anti-inflammatory functions and suppress inflammation.

While the ALS treatment landscape faces hurdles, the ongoing research and clinical trials offer hope for future breakthroughs. The emphasis on understanding the disease's biology and the search for effective biomarkers are crucial steps towards developing more targeted and successful treatments for ALS patients.