On the eve of the weekend Christmas holiday, the U.S. Food and Drug Administration (FDA) approved Biogen’s therapy Spinraza (nusinersen) for the treatment of spinal muscular atrophy in both children and adults. The landmark approval marks the first time the federal agency has approved a therapy that directly treats the orphan disease, which is among the deadliest genetic causes of infant death.
News of the approval has been anticipated by the SMA community for some time now, as ongoing clinical studies for nusinersen have consistently shown the drug to be effective in treating the disease in patients, including infants who are born with SMA Type 1 — considered the deadliest and most progressive form of the disease.
According to an FDA press release, the approval decision was made as a result of consistently positive results from the ENDEAR, EMBRACE, and CHERISH clinical trials sponsored by Ionis and Biogen, all of which produced positive clinical data in terms of drug safety and efficacy.
The ENDEAR clinical trial included 121 patients with infantile-onset SMA who were diagnosed before 6 months of age and who were less than 7 months old at the time of their first dose. In an interim analysis requested by the FDA in order to evaluate the study results as early as possible, 82 of the 121 patients were analyzed. Among this group, 40 percent of patients treated with Spinraza showed marked improvement in the study’s motor milestones, which included head control, sitting, the ability to kick in supine position, rolling, crawling, standing and walking — all milestones observed in the development of healthy babies, but lacking in infants with SMA.
The study also observed that a greater percentage of the participants who took Spinraza survived compared to untreated patients.
The additional open-label studies that Biogen conducted with nusinersen, which allowed infants with SMA type 1 who had not been a part of the original studies to receive the drug, revealed similar findings as those in ENDEAR. Those who participated in these open-label studies ranged in age from 30 days to 15 years at the time of the first dose, and in presymptomatic patients who ranged in age from 8 days to 42 days at the time of first dose.
In an article on SMA News Today from Dec. 8, Dr. Richard Finkel, chief of neurology at Nemours Children’s Hospital in Orlando, Florida, and first author of a key Phase 2 clinical trial (NCT01839656) of nusinersen that was conducted from May 3, 2013, to July 9, 2014, remarked that “with nusinersen, these infants are not only living longer, but they’re living better.”
“SMA is no longer a death sentence for infants,” Finkel added. “This treatment is by no means a cure, but it is more than we’ve ever been able to offer these families before.”
Finkel has had the opportunity to observe patients from this earlier Phase 2 trial who received Spinraza, noting that the drug’s ability to modify SMA’s disease is remarkable.
“It seems that we are turning type 1 SMA into type 2 SMA,” he said in a previous press release. “Two of the children are even walking now, so we can class them as having type 3 SMA. In that sense we can say that nusinersen is a transformative medicine.”
The CureSMA Foundation, which has tirelessly worked to aggressively support the development of promising experimental SMA therapies, called the FDA approval “an historic moment that our community has been working toward for decades,” with Jill Jarecki, PhD, Cure SMA’s chief scientific officer, adding: “This is a landmark day for the SMA community with the first approved drug for the disease. Cure SMA and our entire community have worked together tirelessly for more than 30 years to make this happen. It is important for all of us to stop and celebrate this shared accomplishment that will change and improve the lives of SMA patients.”
Kenneth Hobby, president of Cure SMA, characterized the long road to FDA approval for Spinraza as a team effort: “This has been a story of all groups — families, researchers, companies and the FDA — working together as one community.”
Common side effects that participants in the clinical studies taking Spinraza experienced were upper respiratory infections, lower respiratory infections, and constipation. Some warnings and precautions are associated with the drug as well, including low blood platelet count and toxicity to the kidneys (renal toxicity). Toxicity in the nervous system (neurotoxicity) was also reportedly observed in early animal studies of the drug.
Originally developed by Ionis Pharmaceuticals of Carlsbad, California, in partnership with Biogen, Biogen exercised its option to license Spinraza in July of 2016. Throughout the course of the drug’s development, Ionis and Biogen managed to secure fast track designation, priority review, and the orphan drug status from the FDA, which provides incentives to pharmaceutical companies to focus on developing therapies for rare and orphan diseases such as SMA.
The European Medicines Agency (EMA) validated Biogen’s Marketing Authorization Application (MAA) for Spinraza as a treatment for SMA in October 2016, as well as Accelerated Assessment status from the EMA’s Committee for Medicinal Products for Human Use (CHMP). Biogen has also submitted regulatory filings in Japan, Canada, and Australia, and will initiate additional filings in other countries in 2017.