Isis Pharmaceuticals provides update on ISIS-SMN Rx Phase 2 clinical study in infants with Type I SMA

Isis Pharmaceuticals, Inc. (NASDAQ: ISIS) today provided an update on its ongoing open-label Phase 2 clinical study of ISIS-SMN_Rx in infants with Type I spinal muscular atrophy (SMA). Previously the company reported data from this study on event-free survival, measures of muscle function and assessments of developmental milestones. The data reported today show continued increases in median event-free survival and muscle function scores as well as achievement of developmental milestones. The safety and tolerability profile of ISIS-SMN_Rx to date continues to support further development. Isis is currently collaborating with Biogen to develop and potentially commercialize ISIS-SMN_Rx to treat patients with SMA.

The study was designed to evaluate the safety and tolerability of ISIS-SMN_Rx in infants with Type I SMA and to explore potential efficacy endpoints to support the Phase 3 program. A total of 20 infants with SMA were dosed with either 6 mg or 12 mg of ISIS-SMN_Rx. SMA infants 7 months or younger entered the study sequentially, such that the dosing of infants in the 12 mg cohort began five to 15 months after the first infant was dosed in the 6 mg cohort. Nineteen infants completed the three induction doses and are evaluable for efficacy. Clinical efficacy endpoints include event-free survival, as defined by time to permanent ventilation or death; CHOP-INTEND motor function scores; and assessments of developmental milestones. An analysis as of April 17, 2015 showed that since the last analysis as of September 2, 2014 (seven and a half months ago):

• The median event-free age has increased for infants in both dosing cohorts, from 16.3 months to 19.9 months for the four infants in the 6 mg cohort, and from 11.6 months (n=12) to 16.7 months (n=15) for the infants in the12 mg cohort.
  • For the seven infants in the 12 mg cohort who were in the original group and reported on at the American Academy of Neurology meeting in 2014, the median event-free age has increased from 9.6 months on April 7, 2014 to 21.4 months on April 17, 2015.
• Two of the four infants in the 6 mg cohort remain enrolled in the study and are now older than 27 months of age. In the 12 mg cohort, 11 of 15 infants (73%) are still event-free and older than 15 months of age.
• Muscle function scores have increased from baseline.
• Infants have achieved motor milestones since their baseline evaluations.
• Only a single event has occurred: One infant in the 12 mg cohort required permanent ventilation. There have been no deaths since the previous analysis.

As of April 17, 2015, the median time in study was 13.2 months. The lumbar puncture procedure in infants with SMA has been well tolerated and shown to be feasible. There have been no drug-related serious adverse events (SAEs) and the majority of SAEs were related to respiratory infections. Most of the adverse events (non-SAEs) have been mild or moderate in severity. There were no changes in the safety profile with repeated doses of ISIS-SMN_Rx.