ALS pipeline suffers a major hit following Biogen’s tofersen phase III trial failure, says GlobalData

Biogen’s tofersen has failed to achieve its primary endpoint in the Phase III VALOR study for amyotrophic lateral sclerosis (ALS). This setback is likely to hinder Biogen’s planned filing for United States Food and Drug Administration (FDA) approval in ALS. The company may take a similar approach as it did with its Alzheimer’s disease asset, Aduhelm (aducanumab), and still pursue an accelerated approval using some modestly encouraging data from the secondary endpoints of the trial, says GlobalData, a leading data and analytics company.

GlobalData’s report ‘GlobalData (2020) Amyotrophic Lateral Sclerosis (ALS): Opportunity Analysis and Forecasts to 2029’ reveals that key opinion leaders (KOLs) interviewed by GlobalData stated that despite targeting a small population of ALS patients, tofersen could pave the way for the development of precision medicine approaches that offer disease-modifying benefits for specific genetic subsets of ALS disease*.

Sarah Elsayed, Neurology Analyst at GlobalData, comments: “Although tofersen is being studied for a limited sub-group of ALS disease caused by superoxide dismutase 1 (SOD1) mutations, accounting for only 2% of the total ALS population, this news is hugely disappointing as the drug was believed to be the next breakthrough therapy for this subset of patients.”

Generally, tofersen’s mechanism of action has been highly regarded by KOLs, but some had concerns about the drug’s ability to replicate positive results from earlier trials in larger Phase III trials, a fear which has since played out*.

However, despite tofersen’s failure, Biogen insists that it will not close the door entirely on its ALS program, considering several positive secondary and exploratory endpoints, including reduction of neurofilament (NF) and SOD1 protein.

Ms. Elsayed continues: “Additionally, the combined data from VALOR and ongoing open-label extension portion of the study suggested that tofersen showed signs of slowing disease progression, particularly in patients seeking early treatment.

“Despite this disappointment, a glimpse of hope remains for tofersen and ALS patients with SOD1 mutations. Firstly, it is possible that Biogen may still pursue FDA approval based on secondary endpoint data. Additionally, patients may be able to receive the treatment prior to approval via an ongoing early access program. Finally, as early therapeutic intervention within the pre-symptomatic stage of ALS is thought to massively impact therapy outcomes, Biogen is currently exploring the efficacy of tofersen in delaying disease onset in the Phase III ATLAS trial.”

Tofersen is the second high-profile pipeline asset to fail a Phase III trial for ALS this year, following the failure of Orphazyme’s arimoclomol in May 2021. These failures capture the historical struggle to develop disease-modifying treatments for this rare disease.

Ms. Elsayed concludes: “The high failure rate in ALS clinical trials may be attributed to the disease’s unclear etiology and lack of specific biomarkers. Currently, the only treatment options available for ALS are Rilutek (riluzole) and Radicava (edaravone), neither of which can stop or significantly slow the progression of the disease. Therefore, significant opportunities remain for pharmaceutical companies to address.”

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