Ionis Pharmaceuticals partner Biogen announces results from salanersen study

Ionis Pharmaceuticals (IONS) announced that its partner, Biogen (BIIB), shared topline results from the Phase 1 study of salanersen, an investigational antisense oligonucleotide being developed for the potential treatment of spinal muscular atrophy. Leveraging the same mechanism of action as Spinraza but designed to achieve greater potency, salanersen has the potential to achieve high efficacy and enable once-yearly dosing. Both dose levels tested, 40 mg and 80 mg, given once a year, were generally well-tolerated and led to substantial slowing of neurodegeneration, as shown by reductions in neurofilament. Exploratory clinical outcome data show clinically meaningful improvements in function and attainment of new World Health Organization milestones over one year. These data will be presented at the SMA Research & Clinical Care Meeting hosted by Cure SMA in Anaheim, California. The Phase 1 single ascending dose study was designed to evaluate the safety, tolerability and pharmacokinetics of salanersen. The trial consisted of two parts: Part A, a randomized and placebo-controlled segment in healthy adult male volunteers and Part B, an open-label segment in pediatric participants with SMA who previously received Zolgensma and had investigator-reported suboptimal clinical status. Interim results are from Part B in individuals who received either 40 mg or 80 mg salanersen once a year. In participants with elevated baseline concentrations of neurofilament light chain, indicating ongoing neurodegeneration, initiation of salanersen led to mean reductions in NfL of 70% at 6-months which were sustained through the one-year dosing interval. Salanersen was invented by Ionis using a novel antisense chemistry designed to enhance potency, stability and durability. This advanced molecular design has the potential to deliver long-term results with long-interval dosing. In addition to safety and NfL, exploratory clinical outcome data were evaluated for the subgroup of participants with at least one year of follow-up at the time of the interim analysis. Half of these participants achieved new WHO motor milestones that they previously could not achieve on their own or for which they required assistance, such as walking, crawling, standing or sitting. Furthermore, these participants experienced clinically meaningful improvements in motor function from baseline to one year, including a 3.3-point mean improvement from baseline on the Hammersmith Functional Motor Scale – Expanded and a 5.3-point improvement on the Revised Upper Limb Module. The cumulative interim data from the Phase 1 study indicate that salanersen was generally well tolerated at the 40 mg and 80 mg doses, with most adverse events mild to moderate in severity. The most common AEs were pyrexia and upper respiratory tract infection. Biogen is currently engaging with global health authorities regarding the design of the Phase 3 studies. Ionis discovered salanersen and licensed the global development, manufacturing and commercialization rights to Biogen.