The US Food and Drug Administration (FDA) has accepted a New Drug Application (NDA) for Biogen’s tofersen, an investigational drug for the treatment of superoxide dismutase 1 (SOD1) amyotrophic lateral sclerosis (ALS).
The application, which has been granted priority review, will be discussed at an Advisory Committee meeting on a yet-to-be determined date.
ALS is a rare, progressive and fatal neurodegenerative disease that results in the loss of motor neurons in the brain and the spinal cord that are responsible for controlling voluntary muscle movement.
SOD1-ALS is a rare genetic form of ALS affecting approximately 330 people in the US, and is caused by the production of SOD1 protein that can accumulate to toxic levels in ALS patients with mutations in a specific gene. There is currently no treatment targeted for SOD1-ALS.
Tofersen is an antisense drug, which works by binding to SOD1 mRNA, allowing for its degradation by RN-ase-H in an effort to reduce synthesis of SOD1 protein production.
Included in the NDA are results from a phase 1 study in healthy volunteers, a phase 1/2 study evaluating ascending dose levels, the phase 3 VALOR study and the open label extension study (OLE).
In October 2021, in the phase 3 VALOR study, tofersen failed to produce statistically significant change in functional status for patients with fast-progressing ALS compared to placebo after 28 weeks of treatment.
Despite this, the company announced positive results from a follow-on study suggesting that early administration of the treatment can benefit people living with SOD1-ALS.
Timothy Miller, principal investigator of VALOR and ALS Center co-director at Washington University School of Medicine, said: “The 12-month results showed that individuals with SOD1-ALS who started tofersen earlier experienced a slower rate of decline in clinical and respiratory function, strength and quality of life. These are critical measures for people living with this devastating disease.
“For people in my clinic living with SOD1-ALS, tofersen may meaningfully slow the rapid progression of their disease and the impact it has on their lives.”
During the review period, Biogen will maintain its early access programme for tofersen, now with participants in over a dozen countries, and the OLE and phase 3 ATLAS study in presymptomatic individuals with a SOD1 genetic mutation remain ongoing.