DR. S.V. SINGH, OMBUDSPERSON - E-mail ID: ombudsperson@santosh.ac.in

Biogen Inc. announced the outcome of the U.S. Food and Drug Administration’s (FDA) has approved a new drug called Tofersen for people with SOD1-ALS. Peripheral and Central Nervous System Drugs Advisory Committee meeting on Tofersen, an investigational product for the treatment of superoxide dismutase 1 (SOD1) Amyotrophic Lateral Sclerosis (ALS). The Committee voted unanimously yes (9 yes to 0 no) on the question, “Is the available evidence sufficient to conclude and reasonably likely to predict clinical benefit of Tofersen for treatment of patients with SOD1-ALS”?

How Tofersen works?

Tofersen is an antisense oligonucleotide (ASO) developed by Biogen for the treatment of Amyotrophic Lateral Sclerosis (ALS) caused by mutations in the SOD1 gene. ASOs are short synthetic strands of nucleic acids that can selectively bind to target RNA molecules. In the case of Tofersen, it is designed to specifically bind to the messenger RNA (mRNA) produced by the SOD1 gene. By binding to the SOD1 mRNA, Tofersen helps prevent the production of the toxic SOD1 protein, which is believed to play a role in the degeneration of motor neurons. Tofersen is designed to bind to SOD1 mRNA and degrade SOD-1 mRNA, reducing SOD1 protein production.

In people with this form of the disease, mutations in their SOD1 gene cause their bodies to create a toxic form of SOD1 protein. This toxic protein causes motor neurons to degenerate, resulting in progressive muscle weakness.

What is SOD1-ALS

SOD1-ALS refers to a specific subtype of Amyotrophic Lateral Sclerosis (ALS) caused by mutations in the SOD1 gene. The SOD1 gene dictates translation of an enzyme called superoxide dismutase 1 (SOD1).

SOD1-ALS mutation is estimated to account for approximately 10-20% of all familial ALS cases. It typically follows a similar pattern of symptoms and progression as other forms of ALS, characterized by the gradual degeneration and loss of motor neurons in the brain and spinal cord. This leads to muscle weakness, muscle atrophy, difficulty in speaking, swallowing, and breathing, and eventually, complete paralysis. SOD1-ALS can also affect other systems in the body, such as cognitive function and respiratory function.

Clinical Trials

Clinical trials have been conducted to evaluate the safety and efficacy of Tofersen in patients with SOD1-ALS. One Phase ½ clinical trial called the Nurture study assessed the drug’s safety and tolerability in adults with SOD1-ALS. The study demonstrated encouraging results, showing a reduction in SOD1 protein levels in cerebrospinal fluid, which indicated the target engagement of Tofersen.

Based on the results of the Phase 3 VALOR study and Phase 3 ATLAS study designed to evaluate whether Tofersen can delay clinical onset when initiated in presymptomatic individuals with a SOD1 genetic mutation and biomarker evidence of disease activity.

Although there is currently no cure for ALS, including SOD1-ALS, research efforts are focused on developing treatments that target specific genetic mutations associated with the disease. Tofersen is an example of a targeted therapy being investigated for patients with SOD1-ALS, as mentioned earlier. It aims to reduce the production of the toxic SOD1 protein and potentially slow down the progression of the disease in this specific subset of ALS patients.

On April 25, 2023, Biogen Inc. announced that the U.S. Food and Drug Administration has approved Tofersen (100mg/15ml injection) for the treatment of ALS in adults who have a mutation in the superoxide dismutase 1 (SOD1) gene. This indication has been given accelerated approval. Continued approval for this indication may be contingent upon verification of clinical benefit in confirmatory trial(s).

The Department of Pharmacology, Santosh Deemed to be University, located in Delhi NCR, is one of the major departments that is involved in evaluation of drug efficacy and safety, design and conduct of clinical trials, and the interpretation of the results of clinical studies. Our state-of-the-art research facilities and experienced faculty facilitates comprehensive case studies of patients, allowing us to gain valuable insights into the effectiveness and potential side effects of various medications. Through our rigorous research methodologies, we aim to contribute to the treatment strategies that can improve patient outcomes. Our department collaborates with leading regulatory authorities to ensure that our findings are translated into practical applications. Additionally, we offer specialized courses and training programmes for aspiring pharmacologists, equipping them with the necessary skills to excel in this dynamic field. With a strong emphasis on ethical practices and patient-centric approaches, the Department of Pharmacology at Santosh Deemed to be University continues to make significant contributions towards advancing the field of pharmacology and ultimately enhancing global healthcare. 


Courtesy: Dr Pramod Sharma (MD, DM)

Professor & Head (Pharmacology)                                                                                                          

Santosh Deemed To be University, Ghaziabad.