Presymptomatic Spinraza Treatment Leads to SMA Children Reaching Otherwise Unachievable Milestones, Phase 2 Trial Shows

Presymptomatic infants treated with Spinraza (nusinersen) are able to hit motor milestones that are otherwise unachievable in the natural progression of their condition, spinal muscular atrophy (SMA), with all treated children able to sit without support and most to walk unassisted in a normal timeframe, according to updated results from a Phase 2 trial.

The results were presented at the recent Cure SMA Annual SMA Conference in Anaheim, California, and the 5th Congress of the European Academy of Neurology in Oslo, Norway.

The open-label NURTURE study (NCT02386553) includes 25 patients, who were treated earlier than 6 weeks of age and before having any symptoms. These newborns were most likely to develop SMA type 1 or type 2, as they had two or three copies of the SMN2 gene. All have been receiving Biogen’s Spinraza intrathecally, or via the spinal canal, every four months.

In SMA’s disease progression, a patient with type 1 — the most common and severe form — is unable to sit independently at 3 years of age, and those with type 2 need assistance to do so. These patients are also never able to walk, which markedly differs from the 22 Spinraza-treated infants (88%) in NURTURE who are now able to walk unassisted and most in a normal timeframe, as of March 2019.

“We are seeing patients with two copies [of the SMN2 gene] sitting, we’re seeing them standing, we’re seeing them walking. That’s never seen in the absence of treatment,” Wildon Farwell, executive director of clinical development at Biogen, said in an interview with SMA News Today during the American Academy of Neurology 2019 annual meeting.

As well, no infant in the study has required permanent ventilation. Data presented at the meeting also revealed that all 25 patients were able to swallow. NURTURE is expected to be completed by January 2022.

“These study results demonstrate the durable impact of presymptomatic, proactive treatment on transforming the natural course of this disease,” Darryl De Vivo, MD, a professor of neurology and pediatrics at Columbia University Irving Medical Center, said in a press release. “We are seeing an extensive number of patients continually meeting child motor development milestones and making unprecedented gains in a previously hopeless and often fatal condition.”

“Spinraza is setting patients on a path toward survival, greater mobility and independence, which is helping improve outcomes for patients of all ages,” De Vivo added.

Motor function, as assessed via the CHOP-INTEND score, revealed that the toddlers were approaching the maximum mean score of 64, regardless of the number of SMN2 copies. Of note, SMA type 1 infant average baseline scores are 20–22.

Overall, Spinraza has shown long-term efficacy and safety, with no signs of loss of motor function and no new safety concerns after up to nearly four years of treatment.

“We know how Spinraza can impact children not just over a year or two years, but three, four more years …. I think that’s important for patients,” Farwell said.

Spinraza is available in more than 40 countries, and it remains the only treatment option for SMA patients older than 2. It was originally approved by the U.S. Food and Drug Administration in December 2016 and works by increasing the ability of the SMN2 gene to produce a full-length and functional SMN protein, which is key for the health of motor nerve cells.

According to Biogen, more than 7,500 patients have been treated with Spinraza for up to six years, including commercial-use patients, those in the therapy’s Expanded Access Program, and clinical trial participants.

At the two meetings, Biogen also presented updates from the open-label SHINE extension study (NCT02594124) in children with infantile and later-onset SMA, as well as an analysis in older patients. In addition, the company provided new data on phosphorylated neurofilament heavy chain — a key component of motor neurons — and its potential as a biomarker in SMA.