- The FDA approved ISEMBYLD (apitegromab-mstn) on Sept. 11 for adults and children aged two and over with SMA who are already taking an SMN2-targeted treatment.
- In the Phase 3 SAPPHIRE trial, patients on the recommended dose improved by 2.2 points on the standard motor function scale after a year, while the comparison group declined.
- Fractures occurred in 9% of patients on the recommended dose compared with 2% on placebo, and the label carries a warning about bone fracture risk.
Children with spinal muscular atrophy gained motor function on a newly approved drug, while those on their existing treatment alone carried on losing it.
Spinal muscular atrophy destroys the motor neurons that tell muscles what to do, and the muscles waste away behind them. Existing treatments work on the neuron, and none of them worked on the muscle.
ISEMBYLD is the first that does, and it is designed to be taken alongside the treatment a patient is already on rather than instead of it.
“The approval of ISEMBYLD as the first-ever treatment to directly target the muscular component of SMA is a significant turning point for adults and children who have been waiting for innovative therapeutic options to improve motor function,” said Kenneth Hobby, president of the patient organization Cure SMA.
The SAPPHIRE trial ran in nine countries with 188 patients aged 2 to 21, all of them already on an approved SMN2-targeted treatment. They were randomized to two doses or placebo and infused once every four weeks for about a year.
Patients on the recommended 10 mg/kg dose improved by 2.2 points on the Hammersmith Functional Motor Scale-Expanded. A gain of three points or more was recorded in 34.2% of treated patients, against 13.5% of those on placebo.
Ninety-eight percent of the trial participants chose to carry on into the long-term extension study when it ended.
The safety database covers more than 500 people across all studies of the drug, some of whom have been on it for more than seven years. The most common side effects were upper respiratory tract infections, vomiting, cough, viral infections, headache, gastroenteritis, sore throat and hypersensitivity.
This is not a cure, and it is not a first-line treatment. It is an add-on for people already being treated, and what it offers is movement regained rather than decline slowed.
Manufacturer Scholar Rock says the drug is shipping within days, with a support team to help families work through insurance coverage and where infusions can be given.
Basil Darras, director of the neuromuscular center and SMA program at Boston Children’s Hospital and a principal investigator on the trial, said the priority families name has not changed.
“As neurologists, families consistently tell us that their top priority is gaining motor function, and we are now able to directly target the muscle, not just the motor neuron, for people living with SMA,” Darras said.
