Therapy for Infantile-Onset SMA, Nusinersen, Shows Promise in Phase 3 Study

Biogen and Ionis Pharmaceuticals recently reported that nusinersen, an antisense drug designed to treat spinal muscular atrophy (SMA), ably met the primary endpoint set for an interim analysis of its Phase 3 ENDEAR clinical trial. That study, evaluating nusinersen as a treatment for infantile-onset (consistent with Type 1) SMA, is now closing and the program expanding to include other SMA patients.

Nusinersen is designed to increase production of the SMN protein by altering the splicing of SMN2, a gene closely related to SMN1 that can compensate for the loss or defect of this gene. The drug, which is being developed through a partnership between Ionis and Biogen, has been granted Orphan Drug status and Fast Track designation by the U.S. Food and Drug Administration and Orphan Drug status by the European regulatory agency.

Results from the interim analysis showed that infants treated with nusinersen experienced a statistically significant improvement in the achievement of motor milestones compared to those given placebo. The safety profile of nusinersen was acceptable.

“Today is a hopeful day for the SMA community, which has worked tirelessly to support research and development for this terrible disease. Many of our families have participated in this and other clinical trials in order to advance our understanding of SMA,” Kenneth Hobby, president of Cure SMA, said in a press release. “We are excited about reaching this important milestone, and the opportunity these results create to potentially bring the first treatment option for SMA to patients and families.”

Based on these results, Biogen plans to initiate regulatory filings soon, and has set in motion its option to globally develop and commercialize nusinersen, paying Ionis a $75 million license fee.

“We are grateful to the families participating in the clinical trials, who continue to inspire us,” said Alfred Sandrock, MD, PhD, executive vice president and chief medical officer at Biogen. “We share the community’s sense of urgency as we strive to bring the first treatment for SMA, the leading genetic cause of infant mortality, to families facing this devastating disease.”

ENDEAR will now be stopped and all eligible patients will transfer into SHINE, an open-label clinical trial, and be treated with nusinersen. Results from other endpoints of ENDEAR will be examined when the full data set becomes available, with findings to be presented at upcoming medical meetings.

Patients taking part in the sham-controlled arm of EMBRACE, a Phase 2 clinical trial also in SMA patients, including those with infantile-onset disease, will have the option of being treated with nusinersen.

CHERISH (later-onset consistent with Type 2 SMA) and NURTURE (pre-symptomatic infants) clinical trials — part of the nusinersen clinical development program — will continue as planned in order to gather the clinical data required to determine the efficacy and safety of nusinersen in these populations.

“We are hopeful that nusinersen, if approved, will make a meaningful difference in the lives of patients and families affected by SMA. We look forward to working with Biogen on completing the clinical program and preparing for what we hope is a positive regulatory review,” said B. Lynne Parshall, chief operating officer at Ionis Pharmaceuticals. “Nusinersen is the first antisense drug from our neurological disease franchise to advance to regulatory review, and it illustrates the potential of our antisense technology to address severe diseases.”

Biogen is planning to soon open a global expanded access program (EAP) for eligible patients with infantile-onset SMA (consistent with Type 1). The EAP (NCT02865109)  will include existing nusinersen trial locations in EPA-permiting countries. Once active and required local approvals are in place, participating clinical sites can begin to enroll patients after they have transitioned ENDEAR trial patients to the open-label extension study.

Biogen is responsible for all the development, regulatory and commercial costs and activities related with nusinersen. Ionis is responsible for completing the Phase 3 clinical trials, and will work together with Biogen on regulatory filings and in transitioning clinical programs.