SMA Treatment Spinraza (nusinersen) Shows Positive Results in New Data

In infants with spinal muscular atrophy (SMA), treatment with Spinraza (nusinersen), the first FDA-approved drug for SMA, reduces the risk of death or permanent ventilation, according to new results from the Phase 3 ENDEAR study (NCT02193074).

Biogen presented the data at the British Paediatric Neurology Association (BPNA) annual conference Jan. 11-13 in Cambridge, England.

The FDA recently approved Spinraza for SMA in children and adults, and the European Medicines Agency (EMA) recently validated a Marketing Authorization Application.

In August 2016, the company  reported the results of an interim analysis of ENDEAR. The analysis found that infants receiving Spinraza experienced a statistically significant improvement in the achievement of motor milestones compared to those who did not receive treatment, as measured by the Hammersmith Infant Neurological Examination (HINE).

The ENDEAR study investigated Spinraza therapy in 121 infantile-onset SMA patients, including patients with SMA signs and symptoms at younger than six months and who were screened at younger than seven months. The end-of-study (EOS) efficacy analysis presented at the BPMA conference refers to the 121 patients who had their final study assessment after the interim analysis (conducted in 78 patients) and who attended the six-month follow-up.

Based on the positive results of the interim analysis, the ENDEAR study was stopped and participants transitioned into the SHINE (NCT02594124) open-label study, where all patients receive Spinraza.

In its presentation, Biogen provided data from the pre-specified primary endpoint, time to death, or permanent ventilation from the EOS analysis. The EOS results demonstrated that Spinraza-treated patients had a statistically significant 47 percent reduction in the risk of death or permanent ventilation compared with untreated patients.

Specifically, compared to Spinraza-treated infants, a greater percentage of untreated infants died or required permanent ventilation (39 percent vs. 68 percent, respectively).

“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,” Wildon Farwell, MD, MPH, senior medical director of clinical development at Biogen, said in a press release.

“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,” Farwell added.

Spinraza demonstrated an acceptable safety profile in the trial, with respiratory events and constipation being the most commonly reported adverse events. These adverse events are consistent with those expected in infants with SMA.

Biogen will report further EOS effectiveness and safety results from the ENDEAR trial at a future medical conference.

Spinraza is being tested in two Phase 3 clinical trials: CHERISH (NCT02193074) (childhood-onset) and ENDEAR (infant-onset), and two Phase 2 studies called EMBRACE (NCT02462759) and NURTURE (NCT02386553).

Spinraza is an antisense oligonucleotide (ASO) designed to alter splicing of SMN2, a gene nearly identical to SMN1, to increase production of fully functional SMN protein.

The U.S Food and Drug Administration (FDA) and the European Medicines Agency (EMA) had granted Spinraza special status intended to expedite the investigative review process, including FDA Orphan Drug designation and Fast Track designation in the U.S. and Orphan Drug designation in the E.U.

The EMA’s Committee for Medicinal Products for Human Use (CHMP) granted Accelerated Assessment status for Spinraza.