Motor milestones — a mark of life quality and potential longevity — are evident in a majority of infants with type 1 spinal muscular atrophy (SMA) treated with Spinraza (nusinersen) in a Phase 3 clinical trial, compared to those who received placebo. New interim trial data, in fact, found that 51 percent of Spinraza-treated infants continue to respond with motor-skill improvements, while babies necessarily given a sham therapy have shown no response at all.
New data will be presented Monday at the American Academy of Neurology 2017 meeting, taking place in Boston now through April 28. It builds on earlier trial data that led to Spinraza becoming, in December 2016, the first SMA therapy approved by the U.S. Food and Drug Administration (FDA) to treat SMA types 1–3 in both children and adults. The earlier data had a 41 percent motor-skill improvement in treated babies in a key motor milestone test called HIND, compared to 0 percent in non-treated infants.
The Phase 3 trial, called ENDEAR (NCT02193074), ended early in August 2016, based on its positive interim results in an initial group of 78 babies. The trial’s 122 infants were moved into an ongoing open-label extension study, meaning they are all receiving Spinraza now. This long-term safety and tolerability study, also Phase 3, is called SHINE (NCT02594124) and is expected to end in August 2022.
Spinraza-treated infants in ENDEAR also showed significant improvement in the study’s secondary motor-skill goals. according to the data presented at AAN. In total, 71 percent of these babies had better CHOP INTEND skills (a 16-item motor test of increasing difficulty that’s specifically designed for SMA type 1 infants) than those on placebo (3 percent), and 36 percent showed better evidence of motor neurons working in muscles — compared to 5 percent of non-treated infants — according to the CMAP, or Compound Muscular Action Potential, test.
Spinraza was also seen to lead to “significantly” better event-free survival and overall survival in treated infants, presentation data showed.
HINE, as the Hammersmith Infant Neurological Examination is known, was among the ENDEAR trial’s primary endpoints. The study earlier reported a 41 percent HINE improvement in SMA type 1 infants given Spinraza, which is now up to 51 percent. HINE measures improvements in a baby’s ability to kick, roll over, control its head, sit up, crawl and walk.
“SMA is no longer a death sentence for infants,” Dr. Richard Finkel, first author of a 2016 nusinersen study published in The Lancet, said in December, weeks before the FDA’s approval. Finkel is also chief of neurology at Nemours Children’s Hospital in Orlando, Fla. “This treatment is by no means a cure, but it is more than we’ve ever been able to offer these families before.”
SMA is a hereditary disease that causes weakness and muscle wasting due to the loss of lower motor neurons — specialized nerve cells in the spinal cord and brainstem — that control movement. Type 1 SMA is the disease’s most severe form, usually diagnosed at birth or within the first six months of life, and results from mutations in the SMN1 gene that lead to a shortage of SMN (or survival motor neuron) protein.
Spinraza is an antisense oligonucleotide designed to alter splicing of SMN2, a gene nearly identical to SMN1 that in healthy people produces only a small amount of the SMN protein. The treatment aims to enable SMN2 to produce adequate levels of full-length SMN protein to improve motor neuron survival.
The European Union took a major step toward making Spinraza available to SMA patients in its 28 member countries on Friday, when the Committee for Medicinal Products for Human Use (CHMP) recommended the treatment’s approval. CHMP opinions are generally adopted by the European Medicines Agency, the equivalent of the FDA for the EU.