FDA approval of new drug for SOD1-ALS marks huge step forward in MND treatment

• U.S. Food and Drug Administration (FDA) approves tofersen to treat people with amyotrophic lateral sclerosis (ALS) associated with a mutation in the superoxide dismutase 1 (SOD1) gene (SOD1-ALS)
• Tofersen is an antisense oligonucleotide that targets SOD1 mRNA to reduce the synthesis of the mutant SOD1 protein
• The approval was based on a reduction in neurofilament light (NfL), a blood-based biomarker of axonal (nerve) injury and neurodegeneration

Tofersen, an antisense oligonucleotide therapy which stops mutant SOD1 protein from being made, is the first approved treatment to target a genetic cause of MND. SOD1 mutations are found in 2-3% of the total MND population. In September 2022, we reported the results of a phase 3 trial of tofersen, which showed it could slow and reduce progression of the disease in people living with MND who had a SOD1 mutation (SOD1-ALS).

On 25^th April 2023, the FDA announced the approval of tofersen (now known as Qalsody in the US) to treat people with SOD1-ALS. Tofersen was approved based on the reduction of NfL, a protein that is released into the bloodstream upon injury or degeneration of nerve cells. This is a major step forward, as it is the first time a regulatory decision for an MND treatment has been made based on a biological readout (“biomarker”).

To confirm the clinical benefit of tofersen, a phase 3 randomized, double-blind, placebo-controlled trial is ongoing in individuals who are carriers of the SOD1 genetic mutation, but do not yet have symptoms of the disease. Individual’s NfL levels will be routinely monitored, and if/when NFL starts to increase, treatment with tofersen will be offered, even if other signs of the disease are not apparent. The study will assess the proportion of individuals treated with tofersen who go on to develop symptoms of ALS during the trial compared to placebo.

This month saw the launch of My Name’5 Doddie Foundation’s new research strategy which is focused on expediting the development of new treatments for MND. This news brings hope that effective treatments for MND are now within reach. We will continue to build on the excitement and momentum within the field to accelerate the development of effective treatments for all people living with MND.”

When will tofersen be available in the UK?

Before tofersen is available through the NHS, it must be approved by the UK’s Medicines and Healthcare products Regulatory Agency (MHRA) and recommended by the National Institute for Health and Care Excellence (NICE).

Biogen, the company that has developed tofersen, provided the update below to My Name’5 Doddie Foundation on 28 April, 2023:

• On Tuesday, April 25, Biogen announced that the FDA approved QALSODY™ (tofersen) 100 mg/15mL injection for the treatment amyotrophic lateral sclerosis (ALS) in adults with a mutation in the superoxide dismutase 1 (SOD1) gene. This indication is approved under accelerated approval based on reduction in plasma neurofilament light chain (NfL) observed in patients treated with QALSODY. Continued approval for this indication may be contingent upon confirmation of clinical benefit in a confirmatory trial(s). Biogen is committed to meaningful data generation and addressing FDA requirements.
• In Europe, we are following a separate and independent process. In December 2022 we submitted a Marketing Authorisation Application (MAA) to the European Medicines Agency (EMA) for the approval of tofersen. There is currently an ongoing assessment process during which a committee of experts (led by the Committee for Medicinal Products for Human Use or CHMP) will evaluate the application. The CHMP reviews all the information provided in the submission in order to make a recommendation to the European Commission (EC). The EC then takes a final legally binding decision on whether the medicine can be marketed in the EU.
• In Great Britain, we expect the regulatory pathway for tofersen in the case of a positive EMA CHMP to be the MHRA’s EC Decision Reliance Route Procedure. As you’ll be aware, the reimbursement process is independent from the regulatory process. NICE are currently in the scoping phase to assess how Tofersen will be appraised. We anticipate that the technology appraisal will begin during early July 2023

We will keep the MND community updated on any further updates regarding tofersen and its progress through the review pathway in the UK.