This approved therapy, and others with the potential to one day be a treatment option — like a gene therapy — are bringing considerable hope to the SMA community, Jill Jarecki, chief scientific officer for Cure SMA, said in an interview with SMA News Today.
Her interview coincides with a separate interview with Robert Finkel, chief of the Division of Neurology at Nemours Children’s Hospital in Florida, and principal investigator of the pivotal Phase 3 ENDEAR (NCT02193074) study — data from which has now been published in the New England Journal of Medicine, along with results from an SMA gene therapy trial and an accompanying editorial.
ENDEAR “was a very successful randomized controlled study in symptomatic babies with SMA type 1, and would emphasize … symptomatic,” Finkel said. “We were able to show not only a stabilization in their motor function, meaning that they did not decline further, which is what their natural history would have been. … We actually showed improvement.”
Still, the editorial reminds us that these approaches — while offering unprecedented benefits — have notable limitations.
Ans van der Ploeg, a professor at the Center for Lysosomal and Metabolic Diseases at Erasmus University Medical Center in the Netherlands, pointed to several in her editorial, “The Dilemma of Two Innovative Therapies for Spinal Muscular Atrophy.”
While some babies born with SMA type 1 were able to walk, stand, roll over, and lift their heads after Spinraza treatment — all exceptional achievements — others died, she wrote. Researchers also do not know how well treatment effects will hold up as these children grow older and gain in muscle mass.
These same limitations likely apply to gene therapy, van der Ploeg wrote.
But let us back up a bit to examine the studies that van der Ploeg is discussing.
Highly successful trial
ENDEAR enrolled over 120 SMA type 1 infants into a study where babies were randomly assigned treatment with Spinraza or a so-called sham procedure as a control group. Spinraza is administered through an injection into the spinal canal; control infants had a needle inserted in the back without an injection.
Data in the newly published report, “Nusinersen versus Sham Control in Infantile-Onset Spinal Muscular Atrophy,” showed that 41 percent of Spinraza-treated infants had reached motor development milestones at a six-month interim analysis. None in the control group did.
That data, first revealed in 2016, resulted in the trial being stopped early, which allowed infants in the control group to get Spinraza treatment in an open-label study. It also resulted in a rapid approval of Spinraza in the U.S. only four months later, followed by European approval in 2017.
A final analysis raised to 51 percent the number of treated type 1 infants reaching motor milestones, while those on the sham treatment remained at 0 percent.
Gene therapy shows promise
Many may view the technology behind Spinraza — increasing the production of SMN protein from the “backup” SMN2 gene using so-called antisense oligonucleotides — as catching up with the future.