#AAN2018 – Long-term Spinraza Use Safe, Effective in Treating SMA, Early SHINE Data Show

Long-term treatment with Spinraza (nusinersen) is safe and continues to promote better motor skills and respiratory function in children with spinal muscular atrophy (SMA), according to interim results from a Phase 3 clinical trial.

This early data — from the open-label SHINE study — were in the presentation “Longer-term Assessment of the Safety and Efficacy of Nusinersen for the Treatment of Infantile-onset Spinal Muscular Atrophy (SMA): An Interim Analysis of the SHINE Study.” It was part of Tuesday’s “Emerging Science Platform Session” at the American Academy of Neurology (AAN) annual meeting in Los Angeles that ends Friday.

Spinraza, developed by Biogen, is an approved therapy for all types of SMA that restores to working levels the survival motor neuron (SMN) protein that is largely absent or insufficient in SMA patients. The SMN protein is essential for motor neuron health.

SHINE (NCT02594124) is an ongoing Phase 3 extension study in infants and children with SMA who participated in previous nusinersen investigational trials. As an open-label study, all enrolled are being given the treatment.

Its primary goal is the treatment’s long-term safety and tolerability. Secondary goals look at treatment effectiveness, specifically improvements in motor function — assessed through the Hammersmith Infant Neurological Examination (HINE) Section 2 — and event-free survival. Beyond a patient’s death, this is measured as the post-treatment length of time during which they have no need for respiratory intervention or ventilation.

This interim data exclusively covered patients who moved into SHINE from the ENDEAR study (NCT02193074), a randomized, double-blind, placebo-controlled Phase 3 trial assessing Spinraza’s effectiveness and safety in infants and children with infantile-onset SMA, and likely to develop type 1 disease.

A total of 122 symptomatic infants were enrolled, and randomized to receive either 12 mg of Spinraza or a placebo via spinal injection.

ENDEAR showed significant benefit in motor milestones and respiratory function in the Spinraza-treated group; it was so successful the trial was stopped early so all children could receive the treatment.

As of the June 30, 2017, cutoff date for this analysis, 89 patients had moved to SHINE and were being treated with Spinraza at the 12 mg ENDEAR dose — 65 from the Spinraza group and 24 from the placebo group.

The treatment was seen to be safe and well-tolerated. An adverse event was reported in 83 patients (93%), but no serious events were considered therapy-related. The most frequent were fever and upper respiratory tract infections.

Motor skills improved in all SHINE patients, but those who received Spinraza early — those who started receiving the therapy in ENDEAR — showed greater improvements in motor abilities and developmental milestones than those initially on placebo, data show.

ENDEAR treatment group children also went more than three times longer without a need for permanent ventilation (or death) than those in the initial placebo group, or 73 weeks versus 22.6 weeks, respectively.

These results suggest that Spinraza, as a long-term therapy, is safe and continues to improve motor skills and respiratory function in SMA patients, including those with the disease’s most severe type 1 form.

“These results reinforce SPINRAZA’s unprecedented and compelling efficacy across a broad range of SMA populations, enabling patients to improve mobility and motor function — and, for the most severely affected, increase their chances of survival,” Alfred Sandrock, executive vice president and chief medical officer at Biogen, said in a press release.

“We look forward to continuing to work with healthcare providers, institutions and SMA communities to provide access to SPINRAZA for those in need, no matter their age, disease severity or duration of the disease,” Sandrock added.

An additional analysis, led by researchers at Columbia University Medical Center with support from Biogen, evaluated a subset of data from two multicenter and open-label clinical trials, CS2 (NCT01703988) and CS12 (NCT02052791), that assessed changes in performance during the Six-Minute Walk Test (6MWT) and measures of fatigue.

A total of 14 patients, ages 2 to 15 years, with SMA type 2 or 3 increased by a median of 98 meters (107 yards) the distance they could work in six minutes, while their fatigue levels remained stable or drop  by a median of 3.8 percent over nearly three years of treatment.

“With SPINRAZA treatment, not only were participants able to walk longer distances but they experienced a stabilization or decrease in fatigue while doing so – both of which are meaningful, real-world benefits for individuals with SMA,” said Jacqueline Montes with Columbia University Irving Medical Center, and the study’s lead study author. “Furthermore, the analysis illustrates that SPINRAZA’s benefits continue to grow over time for Type 2 and 3 SMA populations.”

Additional data regarding Spinraza and treatment-associated improvements in motor and respiratory function presented at the AAN conference can be found here.