Biogen announced that its New Drug Application (NDA) for nusinersen, an investigational treatment for spinal muscular atrophy (SMA), has been accepted by the US Food and Drug Administration (FDA) for Priority Review, and that the company’s Marketing Authorization Application (MAA) has been validated by the European Medicines Agency (EMA). Nusinersen had previously been granted Accelerated Assessment status by the EMA’s Committee for Medicinal Products for Human Use (CHMP). The regulatory review process for these applications has now been initiated in the US and EU. Both the Priority Review and Accelerated Assessment designations can reduce the standard review time. If approved, nusinersen would be the first therapy for SMA, a leading genetic cause of infant mortality.
“The FDA and EMA have acknowledged the potential for nusinersen to address the urgent need for an effective SMA treatment by granting special status to the applications, and FDA has shared that they plan to act early on our NDA under an expedited review,” said Michael Ehlers, M.D., Ph.D., executive vice president, head of Research and Development at Biogen. “We are now focused on working with the agencies to hopefully bring this investigational treatment to the SMA community as quickly as possible.
The regulatory filing packages in the US and EU are based on data that demonstrate the clinically meaningful efficacy and favorable safety profile of nusinersen from multiple studies. These include the results from the interim analysis of ENDEAR, the phase 3 study evaluating nusinersen in infantile-onset (most likely to develop Type 1) SMA, as well as open-label data in other patient populations. The ENDEAR interim analysis demonstrated that infants receiving nusinersen experienced a statistically significant improvement in the achievement of motor milestones compared to those who did not receive nusinersen. Data from the other endpoints analyzed were also consistently in favor of the treated infants. Nusinersen was generally well-tolerated, with a favorable safety profile. No adverse events (AEs) were considered related to nusinersen.
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 up to six months of age. The endpoint pre-specified for the interim analysis of the study evaluated the proportion of motor milestone responders from the motor component of the Hammersmith Infant Neurological Examination (HINE). Given the results of the interim analysis, the ENDEAR study is being stopped and participants are able to transition into the SHINE open-label study, in which all patients will receive nusinersen.
Nusinersen is an investigational, potentially disease-modifying therapy for the treatment of SMA that was discovered and developed by Ionis Pharmaceuticals, a leader in antisense therapeutics. Nusinersen is an antisense oligonucleotide (ASO) that is designed to alter the splicing of SMN2, a gene that is nearly identical to SMN1, in order to increase production of fully functional SMN protein.
