Spinraza Found to Improve, Restore, Motor Function in Children with Late-Onset SMA in Long-term Trial

Long-term treatment with Biogen‘s Spinraza (nusinersen) showed clinically meaningful improvement in the motor function of children ages 2 to 15 with late-onset spinal muscular atrophy (SMA), trial data shows.

Spinraza restored motor function and stabilized disease activity over long periods of time in children with type 2 and type 3 SMA, according to data from a Phase 1/2 trial and open-label extension study that allows longitudinal analysis of the disease-modifying treatment.

The findings were reported in the study, “Nusinersen in later-onset spinal muscular atrophy. Long-term results from the phase 1/2 studies,” published in Neurology.

Spinraza became the first disease-modifying treatment to be approved by the U.S. Food and Drug Administration (FDA) for the different forms of SMA in December 2016. The European Medicines Agency (EMA) approved it for the same indications in the E.U. in June 2017.

As of March 31, more than 7,500 SMA patients had been treated with Spinraza in more than 40 countries across the globe.

Spinraza works by increasing the production of the survival motor neuron (SMN) protein that is missing in SMA patients. Because it cannot cross the blood-brain barrier — a highly selective, semipermeable membrane that isolates the brain from the blood that circulates in the body — Spinraza is given by an injection into the spinal canal.

Now, Biogen has announced promising findings from a pooled analysis of data in children with late-onset SMA who completed the multi-center, open-label, dose-escalation, Phase 1/2 CS2 study (NCT01703988), and were eligible to continue treatment with Spinraza during the multiple-dose, long-term CS12 open-label extension study (NCT02052791).

The 253-day CS2 study was designed to assess the safety and tolerability of ascending doses of Spinraza (3, 6, 9 and 12 mg) administered two or three times, over the course of 85 days, by an injection into the spinal canal, in children with late-onset SMA.

The CS12 open-label extension study — spanning 715 days — included patients who completed either the CS2 or a CS10 Phase 1 (NCT01780246) study, and were eligible to continue treatment with Spinraza (four doses of 12 mg). The time frame between the end of CS2 and the beginning of CS12 ranged from 196 to 413 days, depending on the treatment dosage patients had been receiving.

In addition to safety assessments, CS2 included a series of parameters for evaluating the treatment’s effects on patients’ motor function, including the Hammersmith Functional Motor Scale-Expanded (HFMSE), the Upper Limb Module (ULM), the 6-Minute Walk Test (6MWT), and the compound muscle action potential (CMAP).

The pooled analysis included 28 children with SMA (11 with type 2, and 17 with type 3) between the ages of 2 and 15.

After three years of treatment, clinically meaningful improvements were observed in the mean HFMSE scores, with an increase of 10.8 points in SMA type 2 and 1.8 points in SMA type 3 patients; the ULM scores, which increased 4.0 points in SMA type 2 patients; and the 6MWT distances — 92.0 meters in SMA type 3 patients — of children participating in the trials.

These values were significantly higher compared with data from a natural history study in which patients did not receive any intervention. That data showed a decline of 1.7 points in HFMSE scores after three years; an increase of 0.04 points in ULM scores after one year; and a decrease of 1.5 meters in 6MWT distance after one year.

Remarkably, one of the 11 children with SMA type 2, and two of the four children with SMA type 3, who were unable to walk without assistance, regained the ability to walk independently over the course of the trials, showing that Spinraza may restore motor function among patients with late-onset SMA.

The mean CMAP values remained stable throughout the study. None of the study participants had to stop treatment due to adverse events, and no new safety concerns were detected over the course of the studies.

“These data give us new insight on how long-term treatment with Spinraza, over approximately three years, continues to help individuals with later-onset SMA and shows improved clinical efficacy,” Basil Darras, MD, professor of neurology at Harvard Medical School and lead author of the study, said in a press release.

“A longitudinal analysis of this kind, which has not been available until now, provides a wealth of information about the ability to help prevent motor function loss, regain function and safely treat individuals with later-onset SMA. As we change the paradigm of living with SMA, long-term studies of this kind will be essential to understanding the disease,” Darras added.

“These results add to the body of evidence of Spinraza as the foundation of care in SMA broadening its safety and efficacy profile. The data underscore the ability of the therapy to help improve the lives of people with SMA, including those with later-onset SMA, who without treatment typically experience a progressive decline in motor function,” said Wildon Farwell, MD, executive medical director, clinical development, at Biogen.