Nusinersen, an investigational drug for the treatment of spinal muscular atrophy (SMA), is acceptably safe and well-tolerated, and showed encouraging clinical efficacy in infants with SMA type 1, the most severe form of the disease.
These findings, reported in a study published in the journal The Lancet, are based on results of a Phase 2 clinical trial (NCT01839656) of nusinersen, then referred to as IONIS-SMN-Rx, in 20 babies, ages 3 weeks to 7 months, who had an SMN1 homozygous gene deletion or mutation. The trial ran from May 3, 2013, to July 9, 2014.
“It seems that we are turning type 1 SMA into type 2 SMA,” Dr. Richard Finkel, chief of neurology at Nemours Children’s Hospital in Orlando, Florida, and the study’s first author, said in an interview with SMA News Today. “Two of the children are even walking now, so we can classed them as having type 3 SMA. In that sense we can say that nusinersen is a transformative medicine.”
In the trial, researchers injected nusinersen, which consists of a piece of DNA designed to promote the production of the SMN protein from the SMN2 gene, directly into the infants’ spinal fluid.
Results showed that nusinersen had an acceptable safety profile, and slowed disease progression in the majority of patients. In many cases, it also improved survival and motor skills, such as the ability to sit, roll over, and stand — abilities that young children with type 1 SMA often never achieve.
“With nusinersen, these infants are not only living longer, but they’re living better,” Finkel added in a press release. “SMA is no longer a death sentence for infants. This treatment is by no means a cure, but it is more than we’ve ever been able to offer these families before.”
Biogen, the company that is developing nusinersen with Ionis Pharmaceuticals, recently submitted the treatment for approval by the U.S. Food and Drug Administration (FDA) and the European Medicine Agency (EMA). There are also several on-going clinical trials continuing to test its safety and efficacy, and Nemours Children’s Hospital is participating in the Biogen-sponsored expanded access program (NCT02865109) to provide nusinersen to patients of all ages with type 1 SMA until the drug might be approved by regulators.
“Biogen was allowed by the FDA to make this announcement,” Finkel said in his interview with SMA News, “so an FDA approval is likely.”
Among the ongoing nusinersen trials is an open-label Phase 2 study, called NURTURE (NCT02386553), that is currently enrolling infants up to 6 weeks of age at sites in the U.S., Europe and elsewhere, including at the Nemours hospital. Infants in this study are genetically diagnosed to SMA, but pre-symptomatic.
SMA is a genetic disorder affecting approximately one in 11,000 births, and more than half of all cases are type 1. “While SMA is a rare disease, considering that it is the most common fatal disease in infancy, it is not so rare,” Finkel said.
Finkel expanded on the disease’s history in the interview, noting that although SMA was first described toward the end of the 19th century, doctors spent the first 100 years just trying to understand it.
“It wasn’t until the gene was identified that we gained a fundamental understanding of the biologic basis of SMA and targeted treatment strategies could then be explored,” he said. “The idea behind nusinersen was published only nine years ago, and clinical trials already were underway five years later.
“Although nine years is way too long for a family who has a baby with SMA, this is remarkable story of how the revolution in genetics has helped us in the case of SMA. This is just the beginning of a pathway towards more effective treatment for this and other genetic diseases,” Finkel added.