The purpose of SMA Europe is to provide a framework to stimulate collaboration and accelerate translational research pathways in SMA and promote patient care.

  1. Biogen presents Nusinersen data at World Muscle Society Congress 2016

    Biogen presents Nusinersen dataNew data from the clinical program for Nusinersen 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 (EMA) 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 (p<0.0001), defined as the proportion of motor milestone responders as measured by the Hammersmith Infant Neurological Examination (HINE). A responder was defined as a patient who improved in more motor milestone categories (kicking, head control, rolling, sitting, crawling, standing, walking) than worsened.

    Nusinersen was generally well-tolerated, with an acceptable safety profile. No adverse events 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 adverse events 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.

    The Nusinersen Clinical Trial Program

    The nusinersen Phase 3 program is comprised of two registrational studies, ENDEAR and CHERISH. ENDEAR is a thirteen-month study investigating nusinersen in 122 patients with infantile-onset SMA, including patients with the onset of signs and symptoms of SMA at less than or equal to 6 months of age and who are screened at an age of less than or equal to 7 months. Based on insights gained from earlier-stage studies and discussions with regulators, a primary endpoint was added to ENDEAR earlier this year that evaluates the proportion of motor milestone responders from the motor component of the Hammersmith Infant Neurological Examination (HINE). Given the results of the pre-specified interim analysis, the ENDEAR study will be stopped and participants will be able to transition into the SHINE open-label study in which all patients receive nusinersen.

    CHERISH is a fifteen-month study investigating nusinersen in 126 non-ambulatory patients with later-onset SMA, including patients with the onset of signs and symptoms at greater than 6 months and an age of 2 to 12 years at screening. CHERISH was fully enrolled in March 2016.

    Additionally, the SHINE open-label extension study for patients who previously participated in ENDEAR and CHERISH is open and is intended to evaluate the long-term safety and tolerability of nusinersen.

    Two additional Phase 2 studies, EMBRACE and NURTURE, were designed to collect additional data on nusinersen. The EMBRACE study is collecting additional data on a small subset of patients with infantile or later-onset SMA who do not meet the age and other criteria of ENDEAR or CHERISH. NURTURE is an ongoing study in pre-symptomatic infants who are less than or equal to 6 weeks of age at time of first dose to determine if treatment before symptoms begin would prevent or delay the onset of SMA symptoms. All studies are being conducted on a global scale.

    A community statement is expected from Biogen on Monday.


    Biogen press release Saturday 8th October 2016.