Ionis Pharmaceuticals announced today that it has earned a milestone payment of $2.15 million from Biogen for completing the target enrollment of the Phase 3 CHERISH study. The study is designed to support marketing approval of Ionis-SMNrx in children with spinal muscular atrophy (SMA).
B. Lynne Parshall, chief operating officer at Ionis Pharmaceuticals, said:
“Achieving our target enrollment number in CHERISH brings us one step closer to a marketing application for children with SMA. We also plan to complete enrollment in ENDEAR, our Phase 3 study evaluating Nusinersen in infants with SMA, in the first half of this year. This progress sets the stage for Phase 3 data from both of these programs in 2017. We would like to thank the parents and families for their participation in CHERISH as well as the investigators and sites for the achievement of this milestone. We also appreciate the support from the broader SMA community. We, along with Biogen, are committed to advancing Ionis-SMNrx toward the market as rapidly as possible.”
CHERISH, a Phase 3 study of Ionis-SMNrx, is a randomized, double-blind, sham-procedure controlled fifteen month study in approximately 117 children who are non-ambulatory with SMA between the ages of 2 to 12. The study will evaluate the efficacy and safety of 12 mg doses of nusinersen with a primary endpoint of a change in the Hammersmith Functional Motor Scale-Expanded (HFMSE), a validated method to measure changes in muscle function in patients with SMA. Additional efficacy endpoints are also included in the study.
ISIS-SMNRx, now called Nusinersen, is designed to alter the splicing of SMN2, a gene that is closely related to SMN1, to increase production of fully functional SMN protein. The United States Food and Drug Administration (FDA) granted orphan drug status and fast track designation to Nusinersen for the treatment of patients with SMA. The European regulatory agency (EMA) granted orphan drug designation to Nusinersen for the treatment of patients with SMA. Ionis is currently collaborating with Biogen to develop and potentially commercialise the investigational compound, Nusinersen, for the treatment of SMA. Under the terms of the January 2012 agreement, Ionis is responsible for global development and Biogen has the option to license the compound. In addition to the pivotal studies described below, Biogen is operationalizing two Phase 2 studies (NURTURE & EMBRACE) to augment the ongoing Phase 3 program.
Ionis is conducting two Phase 3 studies of Nusinersen. 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 randomised, double-blind, sham-procedure controlled 13 month study in approximately 110 infants diagnosed with SMA. The study will evaluate the efficacy and safety of Nusinersen with a primary endpoint of event-free survival.
In addition to the Phase 3 studies, ENDEAR and CHERISH, Nusinersen is being evaluated in the following 4 Phase 2 studies:
- Biogen is evaluating Nusinersen in an open-label study, NURTURE, in approximately 25 pre-symptomatic newborns who are genetically diagnosed with SMA but presymptomatic.
- Biogen is evaluating Nusinersen in a randomised, double-blind, sham-procedure controlled study, EMBRACE, in 21 patients who do not meet the age and inclusion criteria of ENDEAR and CHERISH studies.
- Ionis is evaluating Nusinersen 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, Ionis 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 Nusinersen in its open-label Phase 2 study.
- Ionis is evaluating Nusinersen in a Phase 2 open-label extension study in 30 children who have completed dosing in one of the earlier Nusinersen studies. Patients in this study have been on treatment for up to 46 months. In June 2015, Ionis reported that it had observed increases in muscle function scores and additional motor function tests in children who received Nusinersen.
Ionis has also completed dosing in three additional Nusinersen studies that evaluated a single or multiple dose of Nusinersen 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.
The following organisations have supported Ionis Pharmaceuticals: Muscular Dystrophy Association, SMA Foundation, Cure SMA and intellectual property licensed from Cold Spring Harbor Laboratory and the University of Massachusetts Medical School.
- Rudnik-Schoneborn S, Berg C, Zerres K, et al. Genotype-phenotype studies in infantile spinal muscular atrophy (SMA) type 1 in Germany: implications for clinical trials and genetic counselling. Clin Genet. 2009;76(2):168-78.
- Finkel RS et al. Observational study of spinal muscular atrophy type I and implications for clinical trials. Neurology. 2014 Aug 26;83(9):810-7.