The U.S. Food and Drug Administration (FDA) has granted conditional approval to Biogen’s tofersen, which has been renamed QALOSDY, for the treatment of those cases of MND associated with mutations in the SOD1 gene.
Mutations in the SOD1 gene are found in as many as 20% of people with familial ALS and in up to 2% of sporadic ALS cases. Such mutations result in a toxic form of the SOD1 protein that accumulates and forms clumps that damage nerve cells.
QALSODY is designed to lower SOD1 levels and preserve nerve cell function. By reducing the amount of SOD1 protein that is produced in cells, the therapy has the potential to slow disease progression and extend survival.
The FDA's conditional approval of QALSODY was based on biomarker data from the Phase 1/2/3 VALOR clinical trial (NCT02623699) and an open-label extension study (NCT03070119). This data showed that the therapy led to marked reductions in blood levels of neurofilament light chain (NfL), a marker of nerve cell damage.
A conditional approval is in contrast to a full approval that would be based on primary outcome data such as an improvement in survival or ALSFRS-R. Further, this conditional approval means that Biogen will be required to continue to collect data on the effects of the treatment and report to the FDA any concerns around ongoing effectiveness.
“The findings are reasonably likely to predict a clinical benefit in patients,” the FDA stated in a press release announcing the approval, adding, “The observed reduction in NfL was consistent across all subgroups based on sex, disease duration since symptom onset, site of onset, and use of other medications for ALS treatment.”
We are currently waiting to hear the exact timeline for Biogen to apply for approval for QALSODY in Australia but we understand that the treatment will continue to be made available to eligible Australian patients through the Biogen extended access program (EAP) that is currently running, until a regulatory decision is made.
This is great news for the MND community with 2 new treatments being approved within 6 months. This also further underlines the value of supporting research across the MND spectrum. Both Tofersen and the previously approved Amylyx therapy, Relyvrio, were developed from basic science research ideas and tested extensively in cell and animal models before transferring to the clinic. Having new treatments that can slow disease progression also affords greater scope for our current care models to be more effective and further prolong survival and improve quality of life. Better disease understanding, earlier diagnosis and new treatments all maximise the effectiveness of care models.