At the end of July 2022, biotechnology company Biogen Inc. shared via news release some exciting updates in regards to its therapy tofersen, an investigational treatment for patients with superoxide dismutase 1 (SOD1) amyotrophic lateral sclerosis (ALS). First, the New Drug Application (NDA) proposes a new pharmaceutical product for marketing and sale in the United States. When submitting an NDA, companies must also supply data from studies highlighting the product’s impact. The FDA recently approved the NDA for tofersen. Additionally, the FDA granted this application Priority Review, meaning it is the FDA’s goal to take action on this application within 6 months. For this reason, the FDA should act on the application by late January 2023.
If eventually approved, tofersen would be the first therapeutic option targeted for those with SOD1 ALS, and form of ALS linked to a genetic mutation. Data included in the NDA included:
- Earlier initiation and treatment with tofersen helped caused sustained neurofilament reduction. Neurofilaments are often associated with, and can be used to identify, neurodegeneration. Additionally, these are associated with earlier mortality and more rapid health dysfunction. Thus, tofersen treatment helped reduce the signs of neurodegeneration while also improving patient outcomes.
- Tofersen therapy was seen to improve quality-of-life.
- Overall, the treatment was relatively safe and well-tolerated, with mild-to-moderate side effects including headache, frequent falls, incidental pain, and back, leg, and arm pain. However, some serious side effects – including myelitis and aseptic meningitis – did occur.
Tofersen: A Brief Overview
The ALS Assocation describes tofersen as:
an antisense oligonucleotide (ASO) targeting SOD1. Tofersen works by blocking the production of the SOD1 protein.
The treatment is administered via a lumbar puncture. Learn more about tofersen here.
What is Amyotrophic Lateral Sclerosis (ALS)?
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease. As nerve cells in the brain, brain stem, and spinal cord degenerate, muscles begin to weaken. People therefore lose their voluntary movement and control. About 90-95% of those with ALS have the sporadic type, which has no discernable cause. However, toxin or substance exposure is hypothesized to play a role. 5-10% of cases are familial, resulting from certain genetic mutations. ALS is more common in males than females. It is a variable disease, meaning it affects people differently. Potential symptoms can (but will not always) include:
- Frequent tripping or falling
- Weakness of the arms, legs, and hands
- Difficulty performing small movements or everyday motions
- Slurred or slowed speech
- Difficulty speaking and/or swallowing
- Psychological stress
- Persistent fatigue
- Unintentional laughing or crying
- Severe and unintended weight loss
- Muscle twitching and cramps
- Poor balance and posture
Understanding SOD1 ALS
SOD1 normally encodes for the production of SOD1, a protein which cleans metabolic waste from cells. However, SOD1 gene mutations cause defective and abnormal SOD1 protein. This protein fails to clean the metabolic waste, but also clumps together throughout the nervous system. An estimated 1-2% of those with sporadic ALS, and 12-20% of those with familial ALS, have SOD1 mutations. The ALS Association explains that over 100 SOD1 mutations have been associated with familial ALS.