Isis Pharmaceuticals announces initiation of ISIS-SMN Rx Phase 3 study in children with SMA

Isis Pharmaceuticals, Inc. (NASDAQ: ISIS) announced today the initiation of a pivotal Phase 3 study evaluating ISIS-SMN_Rx in approximately 120 non-ambulatory children with spinal muscular atrophy (SMA). SMA is a severe and rare genetic neuromuscular disease characterized by muscle atrophy and weakness. The Phase 3 study, CHERISH, is the second Phase 3 study Isis has initiated in a global late-stage clinical development program for ISIS-SMN_Rx. Isis earned a $27 million milestone payment from its development partner, Biogen Idec, for the dosing of the first patient in this study. Isis is also evaluating ISIS-SMN_Rx in the Phase 3 study, ENDEAR, in infants with SMA. Isis is conducting both Phase 3 studies with agreement from the U.S. Food and Drug Administration (FDA) for special protocol assessments, or SPAs.

"CHERISH is the second pivotal Phase 3 study of ISIS-SMN_Rx we have initiated this year. The speed at which we have moved this drug from a preclinical development candidate to a late-stage development reflects the successful collaboration we have with Biogen Idec and the support from the SMA community. It is our hope that this study will build upon the encouraging results we observed in our open-label Phase 2 studies. Both Phase 3 studies are designed to evaluate the efficacy of ISIS-SMN_Rx in either infants or children with SMA and to further assess the safety profile in these patients. We are further encouraged by the FDA's agreement on the trial design and planned analysis for both of these Phase 3 studies on ISIS-SMN_Rx," said B. Lynne Parshall, chief operating officer at Isis Pharmaceuticals. "Together with our partner Biogen Idec, we are also in the planning stages for additional clinical studies as part of our commitment to the clinical program for ISIS-SMN_Rx."

"SMA is a devastating disease that robs people of physical strength by affecting the motor nerve cells in the spinal cord. SMA is the number one genetic cause of death for infants. Children with SMA grow weaker as their disease progresses. Although the genetic cause of SMA is well understood, currently there are no effective drugs available for children with SMA," said Kenneth Hobby, president of Cure SMA. "We applaud Isis for investing in and leading drug development efforts for SMA. We remain hopeful that potential treatments, like ISIS-SMN_Rx, will be able to provide therapeutic benefit."

CHERISH, a Phase 3 study of ISIS-SMN_Rx, is a randomized, double-blind, sham-procedure controlled fifteen month study in approximately 120 children who are non-ambulatory with SMA between the ages of 2-12. The study will evaluate the efficacy and safety of a 12 mg dose of ISIS-SMN_Rx with a primary endpoint of a change in the Hammersmith Functional Motor Scale-Expanded (HFMSE), a validated method to measure changes in muscle function in patients with SMA. Additional efficacy endpoints are also included in the study.

In addition to the current Phase 3 clinical studies ENDEAR and CHERISH, Biogen Idec plans to conduct two additional ISIS-SMN_Rx studies, which could begin in the first half of 2015:

• NURTURE will be a Phase 2 clinical study evaluating ISIS-SMN_Rx in up to 25 pre-symptomatic newborns that are genetically predisposed to the disease.
• EMBRACE will be a Phase 2 clinical study evaluating safety and exploratory efficacy of ISIS-SMN_Rx in approximately 20 patients with infantile or childhood-onset SMA. This study will bridge the gap in a small subset of patients that do not meet the age and inclusion criteria of the current Phase 3 studies ENDEAR and CHERISH.