Amyotrophic Lateral Sclerosis (ALS): Two new drugs failed in clinical trials!

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Amyotrophic Lateral Sclerosis (ALS): Two new drugs failed in clinical trials!

1. C3 therapy pegcetacoplan

On May 25, Apellis Pharmaceuticals announced that it was abandoning its experimental drug pegcetacoplan after results from the Phase II MERIDIAN trials showed it failed to meet its primary endpoint and key secondary efficacy endpoints.

The mid-stage trials, run by Apellis with partner Sobi, enrolled 250 adults with ALS and compared pegcetacoplan with a placebo.

Trial data showed that the investigational treatment showed no statistically significant difference in time to disease progression between the treatment group and the placebo group.

Pegcetacoplan, a C3-targeted therapy that has shown promise in other diseases in the past, was previously approved for the treatment of paroxysmal nocturnal hemoglobinuria and geographic atrophy. According to an Apellis press release, the drug is also being studied in several rare diseases including hematology, nephrology and neurology.

The failure of the trial, while disappointing, was probably to some degree expected. In April, Apellis terminated the open-label portion of the MERIDIAN trial following the recommendation of an independent monitoring committee.

Apellis is the second biopharmaceutical company this week to fail in developing an effective treatment for ALS.

2. Antisense oligonucleotide (ASO) drug WVE-004

On May 23 , the antisense oligonucleotide (ASO) drug WVE-004 developed by Wave Life Sciences was tested for the treatment of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) caused by mutations in the C9orf72 gene lose.

According to the National Institutes of Health, 5-10 percent of ALS cases in the United States run in families. Of these, 25% to 40% were caused by hexanucleotide repeat expansions in the C9orf72 gene. Mutations in this gene have also been identified as a common cause of FTD.

WVE-004 is designed to reduce the levels of the C9orf72 protein. The therapy aims to preserve normal C9orf72 protein by selectively targeting transcript variants containing a hexanucleotide repeat expansion (G4C2) associated with the C9orf72 gene.

In a phase Ib/IIa trials of 35 patients with C9orf72 (C9)-related ALS or frontotemporal dementia, WVE-004 failed to show any clinical benefit after 24 weeks. Based on these data and the lack of biomarkers that might predict clinical benefit, the company is halting development of the program.

Antisense drugs targeting C9-ALS have not performed well recently.

In March 2022, Biogen and Ionis stopped co-developed ASO drug BIIB078 because it also failed to show clinical benefit in phase I trials.

But ASO has also found success in the field of ALS. Biogen’s Qalsody (tofersen) received FDA approval in April for its treatment of superoxide dismutase 1 (SOD1)-ALS .

The SOD1 protein is highly expressed in motor neurons, and the underlying SOD1 gene is mutated in up to 20% of familial cases of ALS and in 2% of all cases.

Amyotrophic Lateral Sclerosis (ALS): Two new drugs failed in clinical trials!

(source:internet, reference only)

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