Update for March 23, 2023

Regulatory Update
 
The FDA accepted the resubmitted NDA for palovarotene after Ipsen provided the additional clinical data that was requested. A PDUFA date was set for 8/16/2023.
 
The FDA rejected the combination of foscarbidopa and foslevodopa for the treatment of motor fluctuations in patients with advanced Parkinson's disease and requested additional information about the pump used to administer the drugs.

Tofersen

• An FDA review of tofersen found that while tofersen did not improve the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale in the Phase III, VALOR trial, the levels of SOD1 protein in cerebrospinal fluid and neurofilament light chain (NfL) in plasma did decrease. NfL has been shown to be significantly elevated in patients with ALS and prognostic for disease progression. SOD1 protein, is a proven contributor to the pathophysiology of SOD1-ALS.
• The FDA’s Peripheral and Central Nervous System Drugs Advisory Committee (PCNSDAC) voted 9 to 0 that that biomarker evidence supports conditional approval for the treatment of superoxide dismutase 1 (SOD1) amyotrophic lateral sclerosis (ALS). The PCHSDAC felt it was reasonably likely that a decrease in plasma neurofilament light chain concentrations would predict clinical benefit of tofersen for treatment of patients with SOD1-ALS. However, the PCHSDAC voted 5 to 3 against recommending full approval due to limitations in the VALOR trial. The PDUFA date for tofersen is 4/25/2023.
  
• Biogen is continuing to evaluate tofersen as a treatment for SOD1-ALS in the ongoing open label extension of the VALOR trial and the 12-month, 150 patient, Phase III ATLAS trial (NCT04856982) in patients who have not developed symptomatic ALS but are at increased risk due to a SOD1 mutation and biomarker evidence of disease activity.