Isis Pharmaceuticals provides update on ISIS-SMNRx Phase 2 study in infants with SMA

Isis Pharmaceuticals, Inc. (NASDAQ: ISIS) today provided an update on its ongoing open label, multiple dose Phase 2 study of ISIS-SMN_Rx in infants with spinal muscular atrophy (SMA).  To date, all four infants in the 6 mg cohort have been in the study for over six months and are now approximately nine and a half  to 16 months in age with an average age of approximately 12 and a half months.  All four infants are alive and none have required permanent respiratory assistance. 

"We are pleased with the tolerability we have observed with ISIS-SMN_Rx to date.  This is the first study to investigate ISIS-SMN_Rx in infants with SMA.  Even though these are interim results from a small number of infants, we are encouraged by the observation that all four infants in the 6 mg cohort are still alive and not on permanent ventilation.  These interim results, while early, provide support for advancing ISIS-SMN_Rx into a Phase 3 study in infants," said C. Frank Bennett, Ph.D., senior vice president of research.  "We look forward to the longer-term results from this ongoing study and plan to report more detailed data at the upcoming American Academy of Neurology meeting in April."

In the ongoing Phase 2 study, doses of either 6 mg or 12 mg are administered intrathecally on Days 1, 15 and 85.  All infants from the 6 mg dose cohort have completed the three initially scheduled doses and are now eligible to receive a maintenance dose of 12 mg six months after their initial three scheduled doses.  In the 12 mg cohort, 10 infants have received at least one dose of ISIS-SMN_Rx to date.  Of these 10 infants, nine still remain in the study.  One infant in the 12 mg cohort succumbed to pneumonia early in the treatment portion of study.  In both cohorts, ISIS-SMN_Rx has been well tolerated.

"Infants with type 1 SMA have the most severe form of this disease.  It is tragic that, because of the severity of their disease, about half of these patients won't make it to their first birthday and most won't make it to their second birthday," said Dr. Tom Crawford, professor of neurology and pediatrics at Johns Hopkins Children's Center.  "A recent study on the natural history of infants with Type I SMA showed that half of infants with Type I SMA had died or been put on permanent ventilation by about 10 months of age.  In that study, this number increases to 80 percent by 18 months of age.  These data are relevant for the study reported today as the characteristics of the infants evaluated in the natural history study are similar to the infants in this study."

Isis plans to present additional detail from this study at the upcoming American Academy of Neurology conference on April 29, 2014. 

Conference Call
At 8:30 a.m. Eastern Time Monday, February 24, 2014, Isis will conduct a live conference call to discuss the top-line results from this study.  Interested parties may listen to the call by dialing 866-652-5200, or access the audio webcast at www.isispharm.com.  A webcast replay will be available for a limited time at the same address.

Isis announced late in 2013 that the Phase 2 infant study was expanded to enroll up to 20 infants and that the first infant was dosed in the 12 mg dose cohort.  Infants from the 12 mg dose cohort will also be eligible to receive an additional 12 mg dose six months after they have completed the initial three scheduled doses.  Infants may enroll in the Phase 2 study if they are between the ages of three weeks and seven months, live in close proximity to a study site and pass screening evaluations conducted at study sites.  The study is being conducted at centers in the United States and Canada.  For further study information, please visit www.clinicaltrials.gov and search for ISIS-SMN_Rx or by the identifier number, NCT01839656. 

ISIS-SMN_Rx is also currently being evaluated in an open-label, multiple-dose, dose-escalation Phase 1b/2a study in children with SMA with Type II and Type III SMA.  In this study, which is designed to assess the safety, tolerability and pharmacokinetic profile of ISIS-SMN_Rx, doses of 3 mg, 6 mg, 9 mg and 12 mg were administered intrathecally. The 3 mg, 6 mg and 12 mg doses are administered on Days 1, 29 and 85.  The 9 mg dose is administered on Days 1 and 85. All children have completed dosing in the initial three dose cohorts and the first child has been dosed in the 12 mg cohort.  The new open-label extension study is designed to provide an additional dose of 12 mg and is open to the more than 50 children with SMA who have completed dosing with ISIS-SMN_Rx in other studies.  For further study information, please visit www.clinicaltrials.gov and search for ISIS-SMN_Rx or by the identifier number, NCT01703988.