Biogen-Ionis Adcomm to Put Promising ALS Biomarker to the Test

On March 22nd, Biogen and Ionis’ experimental therapy for superoxide dismutase 1 (SOD1) ALS, Tofersen, will have its fate in the hands of the FDA’s Peripheral and Central Nervous System Drugs advisory committee. The outcome of this meeting could potentially provide a new hope for those living with the progressive and fatal disease.

Biogen is striving to gain accelerated approval of tofersen, relying on neurofilament light chain (NfL) as a promising biomarker that is expected to indicate clinical benefit.

In July 2022, the FDA accepted the New Drug Application for tofersen under priority review, despite the candidate’s failure to meet the primary endpoint in the Phase III VALOR trial. This is a remarkable decision, showing the FDA’s willingness to push the boundaries of conventional treatments and explore innovative approaches to treating genetic disorders.

The FDA had previously announced plans to hold an adcomm when the NDA was approved, and the date for this event has finally arrived! This is an exciting moment for all involved, as the adcomm is an important step in the drug approval process.

Biogen has declined to comment on the focus of the upcoming advisory committee meeting, but speculation suggests that the committee will be discussing the potential of neurofilament as a viable biomarker for ALS. With this development, Biogen is taking a major step forward in improving the standard of care for those living with this debilitating neurological condition.

The FDA had originally slated Tofersen for review on January 25, 2023, but in October they extended the date to April 25 to account for Biogen’s answers to their questions. This gave the regulator additional time to review the drug more thoroughly.

A Controversial History

SOD1-ALS is a devastating form of ALS that is caused by a mutation in the SOD1 gene. This mutation is responsible for up to 20% of familial ALS cases and 2% of all cases worldwide. There is hope, however, with the development of Tofersen, an antisense drug that has been shown to reduce the synthesis of SOD1 protein production and offer a glimmer of hope for those suffering from SOD1-ALS.

If successful, it would mark a milestone in the fight against ALS, as it would be the first therapy approved for a genetic cause of the disease. This would offer hope to the millions of people worldwide suffering from the neurological condition.

In March 2021, Lisa Stockman Mauriello captured the public’s attention when she sought access to the experimental drug Tofersen, in a bid to save her life from a devastating A5V mutation that typically claims its victims within 12 months. Thanks to the Right to Try act, which was signed into law in 2018, terminally ill patients are given the opportunity to appeal for access to experimental medications that could save or extend their lives. Mauriello’s appeal shone a spotlight on the potential of Tofersen to save lives.

When VALOR was still in its early stages, Biogen decided that it would not be fair to the placebo cohort to expand access to the study beyond the scope of the trial.

On June 25, 2021, Biogen launched a compassionate use program to provide desperately needed treatments for those suffering from a debilitating disease. For Stockman Mauriello, it meant hope. After receiving her first treatment a month later, she sadly passed away just 11 days later. Despite the heartbreaking outcome, her brief moment of hope will never be forgotten.

In October 2021, Biogen announced that tofersen had failed to meet the primary endpoint of the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R). Despite this setback, Biogen pointed to promising trends across secondary and exploratory measures, indicating that tofersen may yet prove to be a beneficial treatment for those living with the condition.

Neurofilament as a Neurodegenerative Biomarker

A year after making initial observations, Biogen released comprehensive 12-month findings from VALOR in the New England Journal of Medicine. The data analysis, which included a combination of the trial and its open-label extension study, provided a more in-depth look at the trends that had been previously identified.

Biogen’s longer-term data showed that earlier initiation of tofersen could slow the decline of function and strength in SOD1-ALS patients. What’s more, Dr. Timothy Miller from Washington University School of Medicine, St. Louis reported a “substantial lowering” of neurofilament levels, which may potentially lead to an inhibition of the underlying disease process.

Biogen will offer an in-depth look at the VALOR and OLE study results, providing a comprehensive analysis of the 12-month integrated data. Get the inside scoop on the latest breakthroughs in the field and learn how these findings could impact the future of medicine and healthcare.

At recent advisory committee meetings for Amylyx’s Relyvrio, neurofilament emerged as a biomarker for ALS, showcasing its potential for use in the diagnosis and treatment of the neurodegenerative disease. According to QurAlis CEO and founder, Kasper Roet, Ph.D., neurofilament has the potential to revolutionize the way ALS is approached.

The need for biomarkers in neurodegeneration is great, and there is a growing confidence in the use of a specific biomarker for ALS. This has the potential to revolutionize the diagnosis of the debilitating disease and open up new avenues for treatments.

In December 2022, Athira Pharma presented biomarker data from the Phase II ACT-AD study demonstrating the efficacy of its Alzheimer’s disease candidate fosgonimeton in reducing both neurofilament and neuroinflammation. This is yet another indication of the increasing importance of neurofilament as a reliable biomarker for Alzheimer’s disease detection.

The eagerly-awaited tofersen adcomm could have far-reaching implications for the use of neurofilament as an effective biomarker of efficacy, particularly in the case of ALS and other neurodegenerative diseases. This decision could be a game-changer in the field of neurological health.

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