On March 22, 2023, via PRNewswire, the FDA announced that its CNS Drugs Advisory Committee voted unanimously in favor of a potential accelerated approval of tofersen to treat people with SOD1 ALS, a rare genetic form of ALS. The vote was based on whether a reduction in neurofilament (NfL) in tofersen-treated patients is likely to forecast clinical benefit.
However, the second question was not as well received. The committee members were asked if the clinical data on tofersen provides significant evidence of its effectiveness in treating SOD1-ALS patients. The committee voted ‘yes’ (3), and ‘no’ (5) with one person abstaining.
Upon further discussion of the aforementioned topics, the committee judged the benefit-risk profile to be favorable when considering the data accumulated on tofersen. A decision will be announced by April 25, 2023.
Tofersen was developed by Biogen to treat patients who have an inherited type of amyotrophic lateral sclerosis (ALS). Results of a clinical trial found that, compared to a placebo, tofersen was unable to demonstrate an improvement in slowing the functional decline of ALS.
Yet Biogen was able to show that tofersen caused substantial reductions of the neurofilament light chain, which is a ‘biomarker’ found in body fluids at elevated levels when there is damage to nerve cells.
A second drug making headlines is Relyvrio. The drug received FDA approval after it demonstrated positive effects on survival and patient function in an ALS clinical trial of 140 participants. However, it is not a cure. The condition of patients who received the drug eventually declined.
On other health issues, in comparison to a placebo, Relyvrio was not significantly better. For example, reducing neurofilament light chain levels.
Neurofilaments are defined as neuroproteins found in the gelatinous liquid (cytoplasm) that fills the inside of a cell within motor neurons in the central nervous system. In ALS, neurons degenerate and neurofilaments flow into the blood and cerebrospinal fluid (CFS).
The Neurology Journal published an ALS study that was designed to confirm serum neurofilaments as biomarkers for ALS therapy. Biomarkers (molecules) indicate a process within the body that may signify a disease or condition.
The ALS study involved biological specimens from 229 ALS patients. Results showed that serum neurofilaments may be considered biomarkers related to the effectiveness of treatment.
In the fall of 2022, Clene acknowledged the failure of Relyvrio to meet its goal in the study. Healey is the first ALS study designed to accelerate development timelines by testing multiple therapies simultaneously. The initial study consisted of five experimental medications.
The Healy study reduces the cost of research by 30% and decreases the length of the trial by 50%. Patient participation increased by 67%. Note, however, that currently its exact role has not yet been determined.
An extension of this trial is ongoing. Initial data is expected in the latter part of 2023.
This year the focus will be on the biomarker and survival data.