CARLSBAD, Calif., March 20, 2013 /PRNewswire/ -- Isis Pharmaceuticals, Inc. (NASDAQ: ISIS) announced that data from the Phase 1 study of ISIS-SMN Rx in children with spinal muscular atrophy (SMA) were presented today at the 65 th American Academy of Neurology (AAN) Annual Meeting by Dr. Claudia Chiriboga, from Columbia University Medical Center. In the presentation, Dr. Chiriboga reported that, in this single-dose, open-label study, ISIS-SMN Rx was well tolerated in children with SMA at all dose levels tested and that improvements were observed in Hammersmith scores, a measure of muscle function, in a number of the children. 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. "SMA is a devastating disease that results in severe muscle weakness and respiratory failure in infants and children. Current treatments are supportive and do not address the underlying genetic cause of SMA, the loss of SMN protein, which is critical to the health and survival of nerve cells responsible for neuromuscular growth and function. ISIS-SMN Rx is designed to address the underlying genetic problem for patients with SMA by increasing the production of functional SMN protein," said Claudia Chiriboga, M.D., associate professor of clinical neurology and pediatrics at Columbia University Medical Center. "I am pleased to report that ISIS-SMN Rx administration was very well tolerated in these young children with a safety profile that supports additional development of the drug. The improvements in muscle function observed in this study following a single dose of the drug were encouraging. For these reasons, I am very excited about the potential benefit of ISIS-SMN Rx for children with this terrible disease." In the presentation titled, 'Results of an Open-Label, Escalating Dose Study To Assess the Safety, Tolerability, and Dose Range Finding of a Single Intrathecal Dose of ISIS-SMN Rx in Patients with Spinal Muscular Atrophy', Dr Chiriboga reported that ISIS-SMN Rx was well tolerated when administered intrathecally as a single dose directly into the spinal fluid and that no safety concerns related to the drug were identified. In addition, the intrathecal injection procedure was well tolerated in children with SMA. Concentrations of ISIS-SMN Rx measured in cerebral spinal fluid were consistent with levels predicted from preclinical studies, indicating that the drug half-life in nervous system tissues is very long and that dosing once every six to nine months is feasible. Although the study was not designed to provide evidence of functional activity, clinically significant, dose-dependent improvements in the Hammersmith Functional Motor Scale-Expanded (HFMSE), a measure of muscle function, were observed in these children. The mean increase in the HFMSE scores observed in the highest dose cohort (9 mg) at 3 months was 3.1 points or a 17.6% increase from baseline, with six of ten patients experiencing an increase of 4 to 7 points. Observed improvements in HFMSE scores equal to or greater than a 4 point increase were distributed by age with half (3) in children under the age of five and half in children five and older. Children who participated in this study are allowed to either enter the ongoing multiple-dose Phase 1b/2a study or a separate re-dosing study. Please click here to access Dr. Chiriboga's AAN slide presentation. "SMA is a heartbreaking disease. Children with SMA are bright and engaging, but often never achieve the simplest motor milestones like walking, crawling, or sitting up. In its most severe form, children do not live beyond 2 years of age. Even in milder cases, SMA patients inexorably grow weaker and experience the loss of the few abilities they did acquire. In addition to motor losses, SMA patients young and old are at constant risk of tragic consequences from simple respiratory infections that you and I take in stride," said Karen S. Chen, Ph.D., chief scientific officer at the SMA Foundation. "The landmark science behind ISIS-SMN Rx is compelling and it has a chance to fill the therapeutic void for SMA and transform the hopes and futures of thousands of patients and families." The Phase 1 study of ISIS-SMN Rx 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, 28 children, including 15 with Type II SMA and 13 with Type III SMA, received ISIS-SMN Rx as a single dose of 1, 3, 6, or 9 mg administered intrathecally. ISIS-SMN Rx concentrations in plasma and cerebral spinal fluid were measured to provide information on the dose concentration and frequency for future studies. In addition, exploratory analyses of changes in motor function were conducted. Gross motor movements were measured in all children throughout the study using the Hammersmith Motor Function Scale-Expanded (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. "ISIS-SMN Rx is our first drug to modify the splicing of RNA to increase the production of a functional SMN protein. This Phase 1 study is the first time that we have administered an antisense drug to patients as young as 2 years of age. We are very encouraged that the drug was safe and that intrathecal dosing was tolerated well by these children even at the highest dose level," said C. Frank Bennett, Ph.D., senior vice president of research at Isis. "Early evidence of activity in these children is encouraging, but it is important to note that this was an open-label study without a control arm," said Stanley T. Crooke, M.D., Ph.D., chairman of the board and chief executive officer at Isis. "We are cautiously optimistic with the observed improvements in muscle function in the higher dose cohort, however, we will need further clinical data from a controlled study to assess the safety and activity of this drug in patients with SMA. We plan to have additional clinical data from our ongoing multiple-dose study in children with SMA by late 2013 or early 2014. We also plan to initiate a Phase 2/3 program in infants this year and a Phase 2/3 study in children in the first half of 2014."