Nusinersen Efficacy for Later-Onset Spinal Muscular Atrophy Types II and III

April 24, 2019—Children with later-onset spinal muscular atrophy (SMA) types II and III treated with nusinersen (Spinraza; Biogen, Cambridge MA) had motor function improvement and disease stabilization over a 3-year period. Of the children with SMA II, 78% (7 of 9) had clinically meaningful improvement 3 years after treatments began; for those with SMA III 36% (4 of 11) had clinically meaningful improvement at that timepoint. 

Children with SMA type III who were able to walk improved the distance they could walk in 6 minutes by an average of 92.0 +/- 21.5 meters, and 2 of the 4 no longer ambulatory children with SMA III recovered their ability to walk independently. 

Type II SMA has typical disease onset at 7 to 18 months; Type III SMA symptoms begin after age 18 months. Participants in the trial were age 2 to 15 years at enrollment. Untreated, children with SMA II typically learn to sit unsupported and stand but never walk independently and may lose the ability to sit or stand; those with untreated SMA III learn to walk but lose that ability over time. 

Motor improvements were measured as scores on the Hammersmith Functional Motor Scale-Expanded (HFMSE), Upper Limb Module (ULM), and 6-Minute Walk Test (6-MWT). Disease progression was measured with compound motor action potential (CMAP) tests and motor unit number estimation (MUNE).

These results are from open-label extension periods of phase 1b/2 studies (NCT01703988and NCT02052791), published in Neurology.

“This study involved kids up to age 15 years at enrollment with SMA types II and III, and they were followed for approximately 3 years, so we were excited to see that the drug can show benefit for these older kids too and that the benefit can extend for this period of time,” said study author Basil T. Darras, MD, of Boston Children’s Hospital and Harvard Medical School and a member of the American Academy of Neurology.