First Treatment Targeting ALS Genetic Cause Could be a Reality with FDA Approval

On July 26, Ionis Pharmaceuticals and Biogen released statements announcing that the United States Food and Drug Administration (FDA) has accepted a New Drug Application (NDA) for the drug toferson, which treats a rare form of ALS (amyotrophic lateral sclerosis). If approved, it will be the first treatment that targets a genetic cause of ALS. 

SOD1 and How Toferson Treats It

SOD1(superoxide dismutase 1) is a rare form of ALS, only affecting about 330 people in the United States. It is far more progressive than other forms, with the average life expectancy of patients with SOD1 being shorter than the three to fives years after symptoms develop in other kinds of ALS. People affected by this disease lose the ability to move, eat, and act independently, with them eventually losing the ability to breathe on their own. 

Toferson is an antisense medication, which is a form of therapy that targets messenger RNA by binding to it and preventing the protein from working as intended. This drug has the potential to treat SOD1-ALS. Currently, there is no other drug that acts as a targeted treatment. 

Pathway to FDA Approval

Biogen submitted the NDA for tofenson, after licensing it from Ionis back in 2018; they are currently seeking approval from the FDA’s accelerated approval pathway based on gathered data that the drug would likely be a clinical benefit. Included in their NDA were the results from a Phase 1 study on healthy subjects, a Phase ½ study that evaluated dose levels, and the Phase 3 VALOR Study.

In October 2021, despite the randomized VALOR study failing to report a significant enough change after its 28 week period in its primary endpoint, trends of reduced disease progression were shown across several secondary and exploratory endpoints. 

On the data, Head of Global Safety and Regulatory Sciences and Interim Head of R&D at Biogen, Priya Singhal, M.D., M.P.H., said in a statement “The available data show that tofersen has the potential to make a meaningful difference for people with SOD1-ALS.”

The FDA has granted the application for toferson a priority review, and given a Prescription Drug User Fee Act action date of January 25, 2023. During this review period, Biogen will maintain its early access program for the drug, with participants in well over a dozen countries now involved. 

Singhal later went on to hope that the FDA would approve accelerated application so that patients suffering from SOD1-ALS could have a treatment available to them in the near future. 

Author

Max Heirich