Risdiplam

Salanersen, which was licensed from Ionis Pharmaceuticals, has the same mechanism of action as Biogen’s approved blockbuster SMA antisense oligonucleotide therapy Spinraza.\n Biogen has pointed to an early readout from a small phase 1 trial as evidence that its antisense oligonucleotide salanersen could help children with spinal muscular atrophy (SMA) who are still struggling to sit independently despite having received Novartis’ Zolgensma.The phase 1 study was split into two parts: a healthy adult volunteer cohort and 24 children aged five months to 12 years with SMA who had previously received the gene therapy Zolgensma and were administered either 40 mg or 80 mg salanersen once a year. Biogen conducted an interim analysis of data from the latter cohort to help decide whether to take salanersen forward into registrational studies.Of the children in the second part of the trial who had elevated baseline concentrations of neurofilament light chain (NfL)—a biomarker of neurodegeneration—salanersen was tied to a mean reduction in NfL of 70% at six months. This reduction was sustained for a year, Biogen explained in a June 25 release.The pharma drilled down further into the interim data to identify eight patients aged between two and 12 years who received 40 mg of salandnersen and had at least a one-year follow-up by the time of the analysis. Half of this subgroup achieved motor function milestones that they had previously not achieved despite receiving Zolgensma, according to Biogen. These included walking, crawling, standing or sitting.“To see a child dosed with gene therapy at one year of age and still unable to sit without support at age five then gain the ability to sit independently just three months after initiating salanersen—that is unexpected,” Valeria Sansone, M.D., Ph.D., Professor of Neurology at the University of Milan and a principal investigator for the trial, said in the release.Sansone noted that today’s data come from “a relatively small cohort,” and a larger trial is still needed to “further understand the effects that salanersen can have in both previously treated and treatment-naïve individuals.”Assessing the safety data across the treated children, Biogen concluded that salanersen had a “generally well-tolerated safety profile” at both the 40 mg and 80 mg doses. Most adverse events were mild to moderate in severity, with no serious adverse events linked to the treatment itself. The most common side effects were fever (affecting 40% of patients) and upper respiratory tract infection (affecting 29%).Salanersen, which was licensed from Ionis Pharmaceuticals, has the same mechanism of action as Biogen’s approved blockbuster SMA antisense oligonucleotide therapy Spinraza but the pharma is aiming for greater potency and once-yearly dosing. Should salanersen make it to market for SMA, it will enter a space already filled not only by Zolgensma and Spinraza, but Roche’s survival motor neuron-2 splicing modifier Evrysdi. Biogen highlighted the fact that it is the only biopharma with both an approved SMA therapy and a potential follow-up in the clinic.Based on today’s data, Biogen said it is engaging with global regulators about the design of a phase 3 trial for salanersen.“Despite the remarkable therapeutic advancements in the field of SMA over the past decade, there remains critical unmet needs,” Biogen’s head of neuromuscular development Stephanie Fradette said in the release. “We are encouraged by the available data and eager to move salanersen into the next stage of development as quickly as possible.”