One patient in the 6-mg group died accidentally, and another underwent permanent ventilation. Two of 11 patients in the 12-mg group died of pulmonary infection, and 1 required permanent ventilation (16 or more hours per day continuously for more than 2 weeks in the absence of an acute reversible illness), although 4 of the patients in this group have not yet received all their doses. At the last follow-up, or at the time of death or permanent ventilation, the median age was 14 months in the 6-mg group and 9.6 months in the 12-mg group (which has not been followed as long).
Scores on the Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) showed increases in 8 of 11 infants who had completed treatment and evaluation. The scores increased by a mean of 5.4 points overall and by 8.3 points in those in the 12-mg group. Incremental milestones on the Hammersmith Infant Neurological Exam were achieved by 9 of 11 infants, including 6 of 7 in the 12-mg group.
The median age at death or need for permanent ventilation is 10.5 months in infants with two SMN2 gene copies, and 85% reach this endpoint at 18 months. Scores on the CHOP-INTEND also declined by 1.27 points per year, according to a study of the natural history of type 1 SMA in 34 patients by Dr. Finkel and his colleagues that is under review for publication.
Compound muscle action potentials measured in the ulnar nerve–innervated abductor digiti minimi and peroneal nerve–innervated anterior tibialis were stable or increased in most infants, he said.
These encouraging results with ISIS-SMNRx have led Isis to begin plans for phase III trials in patients with SMA types 1-3, the investigators said.
The studies are funded by Isis Pharmaceuticals, the Department of Defense, and the National Institute of Neurological Disorders and Stroke. Neither Dr. Finkel nor Dr. Chiriboga had conflicts of interest. Some of the coauthors in each study were employees of Isis.