When Biogen’s experimental treatment for amyotrophic lateral sclerosis (ALS) missed the primary goal of a pivotal study last year, the drugmaker said further analysis could yield better results. Additional data now show that treatment over a longer period of time led to improvement in several measures of the neuromuscular disorder.
The latest clinical trial results were published Wednesday in the New England Journal of Medicine. The data provide further support for the drug tofersen, which has been submitted for FDA review and is expected to receive a regulatory decision in early 2023.
Tofersen is an antisense oligonucleotide, a type of drug made up of small pieces of DNA or RNA. The Biogen drug targets a subset of ALS patients whose disease is caused by mutations in the SOD1 gene. These mutations result in abnormal versions of the SOD1 protein, which are thought to contribute to motor neuron dysfunction and cell death. Tofersen is designed to bind to and degrade SOD1 messenger RNA, which in turn reduces SOD1 protein synthesis.
The primary objective of the randomized, placebo-controlled phase 3 trial of the drug was to evaluate ALS patients on various functional measures at week 28. According to results reported last October, the observed patient improvement was not sufficient to show statistical significance. However, the researchers at the time noted that the results showed a decrease in SOD1 protein and neurofilaments, threads found in neurons that are considered a potential biological indicator of neurodegenerative disease.
Biogen didn’t give up on the drug. In June, the company data analysis presented in which the 28-week randomized study was combined with an open-label 52-week extension study. In this new 52-week analysis, Biogen reported a slower decline in measures such as respiratory function and muscle strength in those who started tofersen earlier — the patients who received the study drug at the start of the study — compared to those who , who started on placebo and switched to tofersen at week 28 to start the extension study. These are the results that have now been published in the New England Journal of Medicine.
Timothy Miller, co-director of the ALC Center at the University of Washington School of Medicine and principal investigator of the tophersen clinical trial, said in prepared statement that in addition to lowering the SOD1 protein, the drug led to a “significant decrease in neurofilament levels, which I interpret as potentially slowing the underlying disease process.” Miller added that looking at results at later time points in the open-label extension study showed “significant clinical benefit.” The New England Journal of Medicine article notes that comparisons of earlier initiation of tofersen versus delayed initiation are still being evaluated in the extension phase of the clinical trial.
The 52-week data was part of Biogen’s request for FDA approval. FDA accepted that filing in July, setting a January 25, 2023 target date for a regulatory decision. At the time, the agency said it planned to convene an advisory committee meeting to discuss the application. The date for this meeting has not yet been set.
The published data for Biogen’s ALS drug comes as ALS drug from Amylyx Pharmaceuticals working its way through regulatory review. Two weeks ago, an FDA advisory panel voted 7-2 in support of recommending approval of this company’s experimental ALS treatment, AMX0035. The FDA’s decision on the drug Amylyx is due by September 29.
Meanwhile, another ALS drug developer, BrainStorm Cell Therapeutics, is trying to get FDA approval. Last year, The FDA called Brainstorm’s analysis of its ALS drug, Nurown, saying that in addition to missing the primary objective of the clinical trial, the results showed no benefit to patients. However, Brainstorm said last month that it plans to do so seek FDA approval from his ALS therapy.
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