Biogen presented new data from the phase III ENDEAR study of SPINRAZA (nusinersen), which demonstrated a statistically significant reduction in the risk of death or permanent ventilation in SPINRAZA-treated infants with spinal muscular atrophy (SMA) compared to untreated infants.
In August 2016, Biogen reported that ENDEAR met its pre-specified primary endpoint at the interim analysis, the proportion of motor milestone responders as measured by the Hammersmith Infant Neurological Examination (HINE). Following the positive interim analysis, Biogen ended the study early so that all participants could have the option to receive SPINRAZA in an open-label extension study. Today, Biogen provided the first presentation of the pre-specified primary endpoint, time to death or permanent ventilation, from the end of study (EOS) analysis. The EOS results presented at BPNA include data from patients’ final study visit, which occurred after the announcement that the study was being stopped and was not part of the interim analysis.
“Although ENDEAR was stopped early based on positive interim results, the study still demonstrated that a significantly greater number of infants treated with SPINRAZA survived and did not require permanent ventilation. These data further underscore the impact SPINRAZA may have on individuals living with this devastating disease,” said Wildon Farwell, M.D., M.P.H., senior medical director, Clinical Development, Biogen. “We are very encouraged that individuals with SMA have already started treatment with SPINRAZA this week in the U.S., and we continue to work closely with regulatory agencies to bring this therapy to patients around the world as quickly as possible.”
SPINRAZA met the pre-specified primary endpoint at the ENDEAR EOS, demonstrating a statistically significant 47% reduction in the risk of death or permanent ventilation (p<0.01). In the EOS analysis, a greater percentage of untreated infants (68%) died or required permanent ventilation compared to infants treated with SPINRAZA (39%).
SPINRAZA demonstrated a favorable safety profile, with commonly reported adverse events including respiratory events and constipation, consistent with those expected in the general population of infants with SMA. Further EOS efficacy and safety results from ENDEAR will be presented at a future medical congress.
ENDEAR was a randomized, double-blind, sham-controlled study in patients with infantile-onset (most likely to develop Type 1) SMA. The EOS efficacy analysis included all patients (n=121) who had their final study visit after the interim analysis (n=78) and had the opportunity to attend the six-month study visit assessment.
Biogen licensed the global rights to develop, manufacture and commercialize SPINRAZA from Ionis Pharmaceuticals, a leader in antisense therapeutics. Biogen and Ionis conducted an innovative clinical development program that moved SPINRAZA from its first dose in humans in 2011 to its first regulatory approval in 2016.
Efficacy and safety data from the ENDEAR interim analysis, as well as open-label data in pre-symptomatic and symptomatic patients with, or likely to develop, Types 1, 2 and 3 SMA, supported the FDA approval of SPINRAZA in the U.S. for the treatment of SMA in pediatric and adult patients, representing the first approved treatment for individuals with SMA.1
In October 2016, the European Medicines Agency (EMA) validated Biogen’s Marketing Authorization Application (MAA) for SPINRAZA, and the EMA’s Committee for Medicinal Products for Human Use (CHMP) granted Accelerated Assessment status. In addition, Biogen has submitted regulatory filings in Japan, Canada and Australia and plans to initiate additional filings in other countries in 2017.