The Food and Drug Administration (FDA) has accepted for Priority Review the New Drug Application (NDA) for tofersen for the treatment of superoxide dismutase 1 amyotrophic lateral sclerosis (SOD1-ALS).

Tofersen is an investigational antisense medicine that reduces the synthesis of SOD1 protein production by binding to SOD1 mRNA, allowing for its degradation by RNase-H. The NDA is supported by data from the 28-week, randomized phase 3 VALOR study ( Identifier: NCT02623699) that evaluated the efficacy and safety of tofersen in 108 adults with ALS and a documented SOD1 mutation.

Patients were randomly assigned 2:1 to receive tofersen 100 mg or placebo. Of these patients, 95 enrolled in the ongoing open-label extension (OLE) study ( Identifier: NCT03070119).

Continue Reading

Findings showed that while the study did not meet the primary endpoint of change from baseline to week 28 in the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R), treatment with tofersen showed trends of reducing disease progression across secondary and exploratory endpoints.

According to 12-month data, the early initiation of tofersen (at the start of VALOR) compared with delayed initiation (6 months later in the OLE study) showed improvements on measures of clinical function (as measured by ALSFRS-R), respiratory function (as measured by slow vital capacity), muscle strength (as measured by the handheld dynamometry megascore), and quality of life (as measured by the 5-item amyotrophic lateral sclerosis assessment questionnaire).

Moreover, in both early- and delayed-start groups, tofersen was associated with a reduction in total CSF SOD1 protein levels, as well as plasma neurofilament levels, a marker of neurodegeneration. At the time of analysis, the median time to death or permanent ventilation (PV) could not be estimated because a majority of patients survived without PV. 

As for safety, the most common adverse events for tofersen in the VALOR and OLE studies were headache, procedural pain, fall, back pain, and pain in extremity; most adverse events were mild to moderate in severity.

The NDA also includes data from a phase 1 study in healthy volunteers and a phase 1/2 study evaluating ascending dose levels of tofersen. 

The FDA is planning to hold an advisory committee meeting to review the data. A Prescription Drug User Fee Act (PDUFA) action date of January 25, 2023 has been set for the application.


  1. Ionis announces that FDA accepts New Drug Application and grants Priority Review of tofersen for a rare, genetic form of ALS. News release. Ionis Pharmaceuticals, Inc. Accessed July 26, 2022.
  2. Ionis partner Biogen announces that results from phase 3 VALOR study and open-label extension of tofersen showed clinical benefit in SOD1-ALS patients. News release. Ionis Pharmaceuticals, Inc. June 3, 2022. Accessed July 26, 2022.

This article originally appeared on MPR