Date: 2015-10-15
Type of information: Initiation of the trial
phase: 3
Announcement: initiation of the trial
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. In addition to the Phase 3 studies, ENDEAR and CHERISH, ISIS-SMNRx is being evaluated in the following four Phase 2 studies: - NURTURE (NCT02386553) in approximately 25 pre-symptomatic newborns who are genetically diagnosed with SMA but presymptomatic. - EMBRACE, in 21 patients who do not meet the age and inclusion criteria of ENDEAR and CHERISH studies. Isis is also evaluating ISIS-SMNRx in a Phase 2 open-label study in 20 infants with SMA. Infants in this study have been on treatment for up to 29 months. In June 2015, Isis reported that it had observed increases in median event-free survival and increases in muscle function scores as well as the achievement of developmental milestones in infants who received ISIS-SMNRx in its open-label Phase 2 study.
Isis is evaluating ISIS-SMNRx in a Phase 2 open-label extension study in 30 children who have completed dosing in one of the earlier ISIS-SMNRx studies. Patients in this study have been on treatment for up to 46 months. In June 2015, Isis reported that it had observed increases in muscle function scores and additional motor function tests in children who received ISIS-SMNRx.
Isis has also completed dosing in three additional ISIS-SMNRx studies that evaluated a single or multiple dose of ISIS-SMNRx in 56 children with Type II and Type III SMA. Children who completed these studies were eligible to roll over into the Phase 2 open-label extension study.
Disease: spinal muscular atrophy
Therapeutic area: Neuromuscular diseases - Rare diseases - Genetic diseases
Country:
Trial
details:
Latest
news: * On October 15, 2015, Isis Pharmaceuticals announced that it has initiated an open-label extension study, SHINE. The SHINE study provides ISIS-SMNRx to infants and children with spinal muscular atrophy (SMA) who have completed their participation in the Phase 3 ENDEAR and CHERISH studies and are eligible to participate in SHINE. All patients in the SHINE study will receive a 12 mg dose of ISIS-SMNRx every four months for infants who completed ENDEAR or every six months for children who completed CHERISH. Isis has earned an $11 million milestone payment from Biogen for the initiation of the SHINE study.
