Data from CS2/CS12, an open-label study of the safety and tolerability of Spinraza published in Neurology

Biogen announced that data from CS2/CS12, an open-label study of the safety and tolerability of Spinraza individuals with later-onset spinal muscular atrophy (SMA), were published in the peer-reviewed journal Neurology. The data show that individuals with later-onset SMA, treated with Spinraza, regained motor function that had been previously lost and that treatment stabilized their disease activity leading to improvements in activities of daily living.The open-label study evaluated 28 patients, aged five to 19 at time of study completion, with later-onset SMA including those most likely to develop SMA Type 2 (n=11) and 3 (n=17) that were treated with Spinraza for more than three years.

In addition to safety, the study also evaluated motor function measures through the Hammersmith Functional Motor Scale–Expanded (HFMSE); Upper Limb Module (ULM); and Six-Minute Walk Test (6MWT). The mean scores for each test showed clinically significant improvements. Key highlights include: Participants with SMA Type 2 increased HFMSE scores by 10.8 points while those with SMA Type 3 improved by 1.8 points. This compares to the natural history of the disease in which individuals with SMA Type 2 and 3 who are not being treated typically experience a 1.7-point decline in HFMSE scores after three years. All non-ambulant children with SMA Type 3 achieved a maximum score of 18 points on the ULM assessment by day 350 and maintained that level of function through day 1,150. This compares to the natural history of the disease in which non-ambulant children with SMA Type 2 and 3 have an average ULM score of 10.23 points with an average 12-month gain of 0.04. Individuals with SMA Type 2 had an average increase of 4.0 points in the ULM assessment up to three years after the baseline assessment. In the natural history of the disease, individuals experience a 0.04 gain over a 12-month period. Participants with SMA Type 3 increased their distance walked by 92.0 meters in the 6MWT in comparison to a 1.5-meter decrease in natural history in the same test after one year. One of the 11 non-ambulant children with SMA Type 2 gained the ability to walk independently through the course of the studies– an achievement that has never been reported in individuals with SMA Type 2 that are not undergoing treatment. Two of the four children with SMA Type 3, who had previously lost the ability to walk, regained the ability to walk independently during the course of the studies, suggesting that reversal of motor function loss may be possible for later-onset individuals treated with Spinraza.

No participants discontinued treatment due to adverse events and no new safety concerns were identified during the three-year observation period.

The analysis is based on patients first treated during the CS2 study who continued treatment in the CS12 extension study. CS2 was a 253-day, multiple ascending dose (3, 6, 9, 12 mg), open-label, multicenter study that enrolled children with SMA aged two to 15 years. CS12 was a 715-day, single-dose level (12 mg) study. Time between studies varied by participant..