Move over Aduhelm, it’s tofersen’s turn

Biogen has clearly not been deterred by the Aduhelm debacle, today shooting for another accelerated approval on the basis of a questionable biomarker. This time the project is the Ionis-partnered tofersen in Sod1-mutated amyotrophic lateral sclerosis, and the biomarker is neurofilament light chain. NfL has been shown to increase with neuronal damage, raising hopes that it could be used to track the progression of various neurological diseases. However, results have not always been consistent: Denali, for example, found an increase in NfL with its Hunter syndrome project DNL310, alongside promising clinical data. Biogen and Ionis, meanwhile, found no clinical benefit with tofersen in the pivotal Valor trial – but they did report a reduction in NfL. Stifel analysts believe that the tofersen data “further complicate the picture around neurofilament's utility”, but expect Biogen to argue that there could be a time lag between NfL and clinical efficacy. This will likely be fiercely debated at an adcom before tofersen’s January 25 Pdufa date. Another ALS adcom is also approaching, with Amylyx’s AMX0035 set to face a panel for the second time in September; that project initially received a 6-4 vote against approval.