Date: 2015-06-22
Type of information: Results
phase: 2
Announcement: results
Company: Isis Pharmaceuticals (USA - CA), now Ionis Pharmaceuticals (USA - CA)
Product: ISIS-SMN Rx (antisense oligonucleotide targeted to the SMN2 gene)
Action
mechanism: antisense oligonucleotide. ISIS-SMNRx is an antisense drug that has been designed to potentially treat all types of childhood SMA by altering the splicing of SMN2 gene, that leads to the increased production of fully functional SMN protein. In January 2012, Isis Pharmaceuticals and Biogen Idec entered into a preferred partner alliance that provides Biogen Idec an option to develop and commercialize ISIS-SMNRx. Under the agreement, Biogen Idec has the option to license ISIS-SMNRx until completion of the first successful Phase 2/3 study. Isis is conducting two Phase 3 studies of ISIS-SMNRx. One Phase 3 study,ENDEAR, in infants with SMA and a second Phase 3 study, CHERISH, in children with SMA. The ENDEAR study is a randomized, double-blind, sham-procedure controlled thirteen month study in approximately 110 infants diagnosed with SMA. The study will evaluate the efficacy and safety of ISIS-SMNRx with a primary endpoint of event-free survival. The CHERISH study is a randomized, double-blind, sham-procedure controlled fifteen month study in approximately 120 non-ambulatory children with SMA. The study will evaluate the efficacy and safety of ISIS-SMNRx with a primary endpoint of a change in Hammersmith Functional Motor Scale-Expanded.
Disease: spinal muscular atrophy
Therapeutic area: Neuromuscular diseases - Rare diseases - Genetic diseases
Country:
Trial
details: In the OLE study, a total of 30 children with Type II or Type III SMA received 12 mg of ISIS-SMNRx dosed intrathecally every six months. Children who enrolled in the OLE study had completed the open-label Phase 2 study of ISIS-SMNRx in which they had received multiple doses of either 3 mg, 6 mg, 9 mg, or 12 mg of ISIS-SMNRx. Clinical endpoints were measured every three months and compared to each patient's Phase 2 baseline score. These endpoints included measurements of muscle function using the Hammersmith Functional Motor Scale-Expanded (HFMSE), the six minute walk test (6MWT) for ambulatory patients and the upper limb module (ULM) test for non-ambulatory patients.
Latest
news: * On June 22, 2015, Isis Pharmaceuticals provided an update on children with spinal muscular atrophy (SMA) who have completed the open-label, Phase 2 multiple-dose study of ISIS-SMNRx and are continuing to receive treatment in an open-label extension (OLE) study. Consistent with earlier observations, increases in muscle function scores and additional motor function tests were observed in children treated with ISIS-SMNRx. In the OLE study, a total of 30 children with Type II or Type III SMA received 12 mg of ISIS-SMNRx dosed intrathecally every six months. Children who enrolled in the OLE study had completed the open-label Phase 2 study of ISIS-SMNRx in which they had received multiple doses of either 3 mg, 6 mg, 9 mg, or 12 mg of ISIS-SMNRx. Clinical endpoints were measured every three months and compared to each patient's Phase 2 baseline score. These endpoints included measurements of muscle function using the Hammersmith Functional Motor Scale-Expanded (HFMSE), the six minute walk test (6MWT) for ambulatory patients and the upper limb module (ULM) test for non-ambulatory patients. An analysis, which was performed on May 15, 2015, showed continued and durable increases in measures of muscle function with 57% of children with SMA achieving increases in HFSME scores of at least three points. Analysis of muscle function measures at the nine month evaluation in the OLE study showed: A mean increase of 3.8 points in HFMSE score (n=22) In a subgroup analysis of children who had incoming HFMSE scores that met the inclusion criteria for the ongoing Phase 3 CHERISH study (³ 10 and ? 54; n=17), the mean increase in HFMSE score was 4.4 points. A mean increase of 55 meters in 6MWT score (n=11). A mean increase of 2 points in ULM test, which measures muscle function on an 18-point scale (n=12) In addition, a review of the safety profile of ISIS-SMNRx in children with SMA provided further support for continued development. Intrathecal administration has been well tolerated and shown to be feasible with no drug-related serious adverse events in either the Phase 2 or the open-label extension studies.
Most adverse events reported as mild or moderate in severity. There were no changes in the safety profile with repeated doses of ISIS-SMNRx.
