Isis Pharmaceuticals announces preliminary data from ISIS-SMNRx Phase 1 study in infants with SMA

Isis Pharmaceuticals, Inc. (NASDAQ: ISIS) announced today that follow-up preliminary data from a single dose, open-label Phase 1 study of ISIS-SMN_Rx in children with spinal muscular atrophy (SMA), show that most SMA children receiving the two highest doses of the drug (6 mg and 9 mg) continued to show improvements in muscle function tests up to 14 months after a single injection of the drug. The Phase 1 data, including these preliminary follow-on data, will be presented at the International Congress of the World Muscle Society by Dr. Kathy Swoboda on Oct. 3, 2013. SMA is a severe and rare genetic neuromuscular disease characterized by muscle atrophy and weakness and is the most common genetic cause of infant mortality. ISIS-SMN_Rx is an antisense drug designed to treat all types of SMA.

The preliminary data reported today is from a follow-up analysis of 24 children with SMA who participated in a Phase 1 single-dose, open-label study of ISIS-SMN_Rx. Analysis of motor function was performed in these children nine to 14 months following a single dose of ISIS-SMN_Rx using the Hammersmith Functional Motor Scale-Expanded (HFMSE). The improvements in HFSME scores were dose dependent with the largest improvements observed in children in the highest dose cohort (9 mg, mean = 5.75). Most children in the 9 mg dose cohort showed continuing improvements during follow up, with no children declining.

"SMA is a devastating disease that results in severe muscle weakness and respiratory compromise in the majority of affected patients. Treating children early in the course of the disease provides the greatest opportunity to reap substantial improvements in muscle strength and function, potentially resulting in a lifetime of benefit. ISIS-SMN_Rx targets the underlying primary cause of SMA, taking advantage of the backup gene, SMN2, present in all SMA patients," said Kathryn J. Swoboda, M.D., professor, department of neurology and director of pediatric motor disorders research program at the University of Utah, School of Medicine.  "Preliminary results from Phase 1 clinical trials reveal a favorable safety profile, and appear to indicate that a single dose of the medication at the higher doses tested to date may result in sustained benefit over many months in some children. Thus, while early, we are excited to continue to work closely with Isis in further studies of ISIS-SMN_Rx in SMA."

"We are pleased with the progress we are making on ISIS-SMN_Rx. Although there was no placebo group, the continuing improvement for up to a year after a single dose observed in this study is encouraging, particularly when considered within the context of the dose response," said B. Lynne Parshall, chief operating officer at Isis.  "Our ongoing Phase 2 program is proceeding well. The 6 mg dose group in our Phase 2 study in infants with Type I SMA has completed dosing. Based on the safety, pharmacokinetic and pharmacodynamic profile of ISIS-SMN_Rx we have observed to date, we have amended the infant study to increase the dose from 9 mg to 12 mg dose. We plan to start dosing this cohort soon.  In our Phase 1b/2a multiple-dose study in children with Type II and Type III SMA, we have completed dosing in all three dose cohorts (3 mg, 6 mg and 9 mg), and we are considering adding a 12 mg dose cohort to this study. The FDA has expressed reservations about increasing the exposure in children with Type II and Type III SMA, and we are in ongoing discussions with them.  We plan to report data from both of these ongoing studies late this year or early next year. We also plan to begin our Phase 3 clinical program early next year."                                             

The Phase 1 study was an open-label, single-dose, dose-escalation study designed to assess the safety, tolerability and pharmacokinetic profile of ISIS-SMN_Rx in medically stable children from age 2-14. In this study, children with Type II or Type III SMA received ISIS-SMN_Rx as a single dose of 1, 3, 6, or 9 mg administered intrathecally. In addition to measurements of drug concentration in plasma and cerebral spinal fluid, exploratory analyses of changes in motor function were conducted.  Gross motor movements were measured using the HFMSE, a modified version of the Hammersmith Functional Motor Scale. The HFMSE is used to assess responses on 33 motor function tasks, each scored on a scale from 0 to 2 and allows for assessment of any SMA patient aged 2 or older. HFMSE has demonstrated good test-retest reliability in other studies.

Data from this study was reported at the American Academy of Neurology in March 2013, showing that a single-dose of ISIS-SMN_Rx was well tolerated in children with SMA at all dose levels tested and that improvements were observed in HFMSE scores in a number of children, with a mean increase in HFSME scores for the 9 mg cohort at three months was 3.1 points. The data to be reported at the World Muscle Congress in October is a follow on analysis of HFMSE in 24 children who had completed the Phase 1 study.