Isis Pharmaceuticals provides update on ISIS-SMN Rx Phase 2 study in children with SMA

Isis Pharmaceuticals, Inc. (NASDAQ: ISIS) today provided an update on children with spinal muscular atrophy (SMA) who have completed the open-label, Phase 2 multiple-dose study of ISIS-SMN_Rx and are continuing to receive treatment in an open-label extension (OLE) study. Consistent with earlier observations, increases in muscle function scores and additional motor function tests were observed in children treated with ISIS-SMN_Rx. Isis is currently collaborating with Biogen to develop and commercialize ISIS-SMN_Rx to treat patients with SMA.

"The natural course for children with untreated type II or type III SMA typically experience loss of muscle function that develops slowly and continually over time, a sustained increase of three or more points in HMFSE scores represents a significant departure from the natural course and is unusual for these children," said Dr. Darryl De Vivo, Professor of Neurology and Pediatrics, Columbia University Medical Center.

In the OLE study, a total of 30 children with Type II or Type III SMA received 12 mg of ISIS-SMN_Rx dosed intrathecally every six months. Children who enrolled in the OLE study had completed the open-label Phase 2 study of ISIS-SMN_Rx in which they had received multiple doses of either 3 mg, 6 mg, 9 mg, or 12 mg of ISIS-SMN_Rx. Clinical endpoints were measured every three months and compared to each patient's Phase 2 baseline score. These endpoints included measurements of muscle function using the Hammersmith Functional Motor Scale-Expanded (HFMSE), the six minute walk test (6MWT) for ambulatory patients and the upper limb module (ULM) test for non-ambulatory patients.

An analysis, which was performed on May 15, 2015, showed continued and durable increases in measures of muscle function with 57% of children with SMA achieving increases in HFSME scores of at least three points.

Analysis of muscle function measures at the nine month evaluation in the OLE study showed:

• A mean increase of 3.8 points in HFMSE score (n=22)
  • In a subgroup analysis of children who had incoming HFMSE scores that met the inclusion criteria for the ongoing Phase 3 CHERISH study (³ 10 and ≤ 54; n=17), the mean increase in HFMSE score was 4.4 points.
• A mean increase of 55 meters in 6MWT score (n=11).
• A mean increase of 2 points in ULM test, which measures muscle function on an 18-point scale (n=12)

In addition, a review of the safety profile of ISIS-SMN_Rx in children with SMA provided further support for continued development.

• Intrathecal administration has been well tolerated and shown to be feasible with no drug-related serious adverse events in either the Phase 2 or the open-label extension studies.
• Most adverse events reported as mild or moderate in severity.
• There were no changes in the safety profile with repeated doses of ISIS-SMN_Rx.

"In these studies using multiple measurements of muscle and motor function changes, we observed encouraging results that were consistent with earlier results from our open-label Phase 2 study. Taken together, these data suggest that ISIS-SMN_Rx could provide benefit to patients with SMA beyond halting their disease progression," said C. Frank Bennett, Ph.D., senior vice president of research at Isis Pharmaceuticals. "The safety and tolerability profile that we have observed across all of our ISIS-SMN_Rx studies support the ongoing Phase 3 programs in both infants and children with SMA."