Regulatory Applications for SMA Therapy Nusinersen Accepted in US and EU


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Spinraza for later-onset SMA

The U.S. Food and Drug Administration (FDA) has accepted Biogen‘s new drug application for nusinersen, an investigational drug for spinal muscular atrophy (SMA), for priority review.

The company also announced that the European Medicines Agency (EMA) validated nusinersen’s marketing authorization application (MAA).

If nusinersen is approved, it will become the first therapy for SMA. Biogen plans to market nusinersen as Spinraza. The name has been conditionally accepted by the FDA and the EMA’s Committee for Medicinal Products for Human Use (CHMP), which previously granted nusinersen accelerated assessment status.

Nusinersen is a novel, potentially disease-modifying therapy. It is an antisense oligonucleotide (ASO) created to alter the splicing of SMN2, a gene that is nearly identical to SMN1, to increase production of fully functional SMN protein.

ASOs are short synthetic strings of nucleotides designed to selectively bind to target ribonucleic acid (RNA) and regulate gene expression. With this technology, nusinersen can potentially increase the amount of functional SMN protein in children and infants with SMA.

With the FDA’s priority review and CHMP’s assessment status, accelerated regulatory review for nusinersen is now on track in the U.S. and the European Union.

U.S. and E.U. regulatory filing packages are based on positive safety and effectiveness data from clinical trials. These include the results from an interim analysis of the Phase 3 ENDEAR trial (NCT02865109), a 13-month study evaluating how 122 participants with infantile-onset SMA (most likely to develop type 1) – including children with the signs and symptoms of SMA – reacted to nusinersen.

Interim analyses have shown statistically significant improvements in motor milestones, and the drug was generally well-tolerated, with a favorable safety profile and no significant adverse events. Given these results, ENDEAR will be stopped to allow participants to switch to the open-label SHINE study (NCT02594124), designed to evaluate the long-term safety and tolerability of nusinersen, in which all patients will receive the investigational product.

ENDEAR is included in nusinersen’s Phase 3 clinical trial program, together with CHERISH (NCT02292537), a 15-month study evaluating nusinersen in 126 non-ambulatory participants with later-onset SMA, including those with early onset of signs and symptoms (at six months of age, minimum) and with screening at ages from 2 to 12.

Two Phase 2 studies, EMBRACE (NCT02462759) and NURTURE (NCT02386553), are collecting additional data on nusinersen. EMBRACE is studying patients who didn’t meet the age and other criteria of ENDEAR and CHERISH. NURTURE will assess pre-symptomatic infants up to six weeks old when they were given their first dose of nusinersen to determine if treatment before symptoms begin would prevent or delay the onset of SMA symptoms.

NURTURE is currently currently enrolling patients for the study.

“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,” Michael Ehlers, MD, PhD, executive vice president and head of research and development at Biogen, said in a press release.

“We are now focused on working with the agencies to hopefully bring this investigational treatment to the SMA community as quickly as possible.”