FDA Grants Priority Review of Tofersen for SOD-1 Amyotrophic Lateral Sclerosis
The Food and Drug Administration (FDA) has agreed to priorty review of a New Drug Application (NDA) for tofersen (Biogen, Cambridge, MA) for treatment of superoxide dismutase-1 (SOD1) amyotrophic lateral sclerosis (ALS). According to the filed data for the NDA, tofersen slowed decline across measures of clinical and respiratory function, strength, and quality of life
Tofersen did not meet the primary outcome measure in the VALOR phase 3 clinical trial (NCT02623699) which was significant improvement on the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) scale. However, based on reductions in the biomarker neurofilament light (NfL, which has been shown to predict rate of clinical decline in ALS, accelerated approval is being sought.
Additionally, trends in pooled data and open-label periods suggest reduced disease progression across multiple secondary and exploratory endpoints with tofersen treatment. in the open-label extension period of the VALOR study participants treated with tofersen vs placebo in the double-blind portion of the trial had maintained muscle strength (measured with dynamometry) at week 40. At week 52, similar plateauing and maintenance of muscle strength were seen in those had received placebo for the first 12 weeks.
On the ALS Assessment Questionnaire, individuals who received tofersen 28 weeks earlier had a slower rate of decline that resulted in a 10.3% difference at 52 weeks (P=.004). Those who received tofersen earlier had significantly better quality of life, as measured with the EuroQOL-5 Dimension 5-Level Questionnaire (adjusted mean difference 0.2 on scale of -.594 to 1.0; 95% CI: 0.13-0.32; P<.0001).
“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,” said Timothy Miller, MD, PhD, principal investigator of VALOR and ALS Center co-Director at Washington University School of Medicine, St. Louis. “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.”
Serious treatment-emergent adverse events included myelitis (2%), aseptic meningitis (2%), increased intracranial pressure (ICP; 1%), papilloedema (1%), lumbar radiculopathy (1%), and other neurologic disorder (1%) in the 104 participants treated with tofersen in both the placebo-controlled and open-label studies.
The application has been granted priority review and a Prescription Drug User Fee Act action date was set for January 25, 2023. An advisory committee meeting is being planned for the application with no determined date yet.