New data from the clinical program for nusinersen, an investigational treatment for spinal muscular atrophy (SMA), were presented by Biogen and Ionis Pharmaceuticals in the late-breaking session at the 2016 World Muscle Society Congress in Granada, Spain. The presentations included safety results from the interim analysis of the Phase 3 ENDEAR study in infantile-onset SMA (most likely to develop Type 1), encouraging preliminary results from NURTURE, a Phase 2 open-label study in pre-symptomatic infants, and a recent analysis of the ongoing Phase 2 open-label study in patients with later-onset SMA (consistent with Types 2 or 3).

“We continue to be encouraged by the consistently positive results with nusinersen across our clinical program, including our first data in infants treated before they show signs of the disease,” said Wildon Farwell, senior director SMA clinical development at Biogen. “NURTURE is the first study to evaluate an investigational therapy in pre-symptomatic infants genetically at risk for SMA. In this analysis, infants treated for up to one year achieved motor milestones in timelines more consistent with normal development than what is observed in the natural history of patients with Type 1 SMA.”

Biogen has completed the rolling submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for the approval of nusinersen. Submission of the Marketing Authorization Application to the European Medicines Agency is planned in the next week. Biogen will initiate regulatory filings in other countries in the coming months.

Interim Data from Phase 3 ENDEAR Trial

In the interim analysis of the controlled, Phase 3 ENDEAR study in infantile-onset SMA, infants treated with nusinersen demonstrated a statistically and clinically significant improvement in the primary endpoint (pNusinersen was generally well-tolerated, with an acceptable safety profile. No adverse events (AEs) were considered related to treatment. Based on the results of the positive interim analysis, patients who elect to do so will be transitioned to SHINE, an open-label extension study, in which they will be able to receive nusinersen. Following the transition of patients, the ENDEAR study will close. Detailed efficacy data will be presented at a future medical conference once participants complete their final study visit in ENDEAR.

First Clinical Data in Pre-Symptomatic SMA Patients

The interim analysis of the ongoing, open-label, 30-month, Phase 2 NURTURE study showed that nusinersen-treated infants exhibited improvements in motor function and motor milestones such as full head control, independent sitting, standing with support, standing unaided, and walking with support, as measured by validated scales. The primary endpoint was defined as time to respiratory intervention (invasive or non-invasive ventilation for 6 hours or more per day continuously for 7 or more days or tracheostomy) or death. At the time of the interim analysis all patients were alive and did not require respiratory intervention. This analysis included data from 13 genetically diagnosed, pre-symptomatic SMA patients who had been enrolled for a minimum of 64 days and up to 13 months. Three infants experienced AEs considered possibly related to nusinersen, all of which were resolved. In addition, no infants have discontinued or withdrawn from the study and no new safety concerns have been identified. The NURTURE study is currently active and enrolling.

“These findings reinforce the potential of nusinersen, and we remain focused on bringing this investigational treatment to patients and families as quickly as possible,” noted C. Frank Bennett, Ph.D., senior vice president of research and leader of the neurological disease franchise at Ionis Pharmaceuticals. “We are grateful for the commitment and contributions of the investigators, patients and families that have made the rapid development of nusinersen possible across a range of patients.”

Supportive Data from Ongoing Open-label Phase 2 Trials

In addition, exploratory efficacy and safety data from the open-label Phase 2 trials (CS2/CS12) in twenty-eight patients with later-onset SMA (consistent with Types 2 or 3), showed that children with SMA treated with nusinersen exhibited improvement on several measures of motor function for up to nearly three years. These results contrast to the stable or slow decline in scores typically observed in patients with later-onset SMA over time. Overall, most AEs were mild to moderate and not considered related to nusinersen and there were no serious adverse events (SAEs) related to the study drug.

EMA Filing

Biogen also announced that they have filed a marketing authorization application (MAA) for nusinersen with the European Medicines Agency. Regulatory review varies but, in general, standard review in the EU averages between 13-15 months. Recently, the EMA’s Committee for Medicinal Products for Human Use (CHMP) granted Accelerated Assessment to nusinersen, which can reduce the standard review time from 210 days to 150 days. However, the actual timing may vary depending upon the specifics of a submission’s review.

Cure SMA Provides Seed Funding for Nusinersen

Starting in 2003, Cure SMA provided the seed funding needed to begin investigation into this therapeutic approach. The intellectual property generated with our funding was then licensed to Ionis Pharmaceuticals to create nusinersen

Cure SMA would like to thank and acknowledge Cold Spring Harbor Laboratory (CSHL) and the University of Massachusetts Medical School for generating critical intellectual property for the program that was licensed to Ionis Pharmaceuticals. We specifically thank Dr. Adrian Krainer and his colleagues at CSHL for years of dedication to and hard work on the preclinical development of nusinersen for SMA, and Drs. Ravindra Singh and Elliot Androphy for their work funded by Cure SMA in originally identifying the ISSN1 gene sequence, which is the sequence targeted in nusinersen. In addition, Drs. Krainer and Androphy are long standing members of the Cure SMA Scientific Advisory Board.