All 25 pre-symptomatic infants treated with Biogen’s Spinraza (nusinersen) in a Phase 2 clinical trial of spinal muscular atrophy (SMA) did not require permanent ventilation and exhibited motor improvements, according to a preliminary analysis.
All infants showed improvements at the cut-off date for the preliminary evaluation on July 5, 2017.
Findings from the interim results, “Nusinersen in Infants Who Initiate Treatment in a Pre-Symptomatic State of SMA: Interim Efficacy and Safety Results from the Phase 2 NURTURE Study,” was presented at the 2018 Muscular Dystrophy Association (MDA) Clinical Conference, held March 11-14, 2018, in Arlington, Virginia.
A case series describing the benefits of Spinraza in teens and young adults with SMA was also presented.
“These results reinforce Spinraza’s effectiveness as the first and only approved treatment for SMA and demonstrate once again the benefit it can bring to individuals with SMA, including infants, teens and young adults,” Alfred Sandrock, MD and PhD, executive vice president and chief medical officer at Biogen, said in a press release.
“Spinraza is supported by the largest well-controlled SMA clinical development program conducted to date and we are committed to ongoing research in SMA,” Sandrock added. “Biogen looks forward to working with healthcare providers and institutions in order to provide teens and young adults with SMA access to Spinraza.”
SMA is caused by mutations in the SMN1 gene, leading to insufficient or a complete lack of the SMN1 protein, which is key for motor neurons and muscle function.
The SMN2 gene also codes for the SMN protein, but generates much lower protein levels. Spinraza acts on the SMN2 gene to increase the levels of a full-length SMN protein.
In the NURTURE trial, 25 children 6 weeks or younger received the medication. No child had shown symptoms of SMA at the start of treatment. Fifteen children had two copies of the SMN2 gene, which is indicative of future development of type 1 SMA, and 10 infants had three copies, and were most likely to develop type 2 SMA.
By the time of the analysis, infants had been followed for over 25 months, which is beyond the time frame when most type 1 SMA infants would require permanent ventilation or had died.
“The NURTURE findings document the continuing benefits that SPINRAZA provides for patients with SMA who initiated treatment in early infancy while clinically pre-symptomatic, including age-appropriate developmental gains in motor function and motor milestone achievements,” said Darryl C. De Vivo, MD, the study’s lead author from Columbia University.
“The treated infants in the NURTURE study had genetic SMA and were likely to clinically develop Type 1 or 2, yet with enough observation time they have all achieved independent sitting and the majority have developed the ability to walk,” he added.
The SMA infants have shown a continued improvement in motor function and many are still improving or maintaining high motor function scores at a point well beyond the stage when infants with type 1 SMA would have shown a significant decline.
Data analysis also revealed that Spinraza was well-tolerated and did not induce any new safety concerns.
The motor improvements in NURTURE correlate with those of the CHERISH Phase 3 study (NCT02292537) that evaluated Spinraza in 126 children with later-onset SMA, defined as showing symptoms after six months of age and likely corresponding to types 2 and 3.
Younger children and those within 25 months of disease showed the greatest benefits. Similar findings were also observed in the ENDEAR Phase 3 study (NCT02193074) in children with infantile-onset SMA, most likely type 1.
Also presented at the 2018 MDA conference was a case series titled, “Nusinersen Experience in Teenagers and Young Adults With Spinal Muscular Atrophy.”
Spinraza was given to five teenagers — one type 2 and four type 3 SMA — ages 14 or 15 at the start of the study, and 17 to 19 at their last visit in the respective extension study.
All patients received multiple doses of the therapy for more than 2.5 years. Analysis of standardized scales and tests showed improvements in motor function, arm function, and exercise capacity, as well as stable or improved scores on the impact of SMA on caregivers.
“The case series demonstrated Spinraza’s effectiveness in teens and young adults with SMA Type 2 or 3,” said the study’s lead author, John Day, an MD and PhD, Stanford University.
“The study participants demonstrated stable or slightly improved motor function and quality of life during two years of treatment — and even afterward, we have continued to see improved and maintained stability and motor benefits with Spinraza,” he said.
These improvements are an important contrast to the typical reduction in motor function and in health-related quality of life of untreated teens and young adults with SMA, Day observed.
Spinraza is the first and only approved medicine for the treatment of SMA and is currently approved in the U.S., E.U., Canada, Brazil, Japan, Switzerland, Australia, and South Korea.
Including both commercial access and use of Spinraza in clinical trials, Biogen estimates that over 3,200 SMA patients are being treated with Spinraza worldwide.