Pivotal Phase 3 Study in Non-Ambulatory Children with Spinal Muscular Atrophy Begins

James Radke

Isis Pharmaceuticals has begun a second pivotal Phase 3 study evaluating ISIS-SMNRx in non-ambulatory children with spinal muscular atrophy (SMA). 

SMA is a genetic condition that leads to a deficiency in the spinal motor neuron (SMN) protein as a result of mutations of the survival motor neuron 1 (SMN1) gene. The severity of SMA correlates with the amount of SMN protein. Generally, the muscles most affected are those near the shoulders, hips, thighs and upper back. Muscles used for breathing and swallowing may also be affected. Infants with Type I SMA produce very little SMN protein and have a life expectancy of less than two years. Children with Type II have greater amounts of SMN protein but still have a shortened lifespan and are never able to stand independently. Children with Type III have a normal lifespan but accumulate life-long physical disabilities as they grow.

The Phase 3 CHERISH study, is the second Phase 3 study Isis has initiated for ISIS-SMNRx. The other Phase 3 study, ENDEAR, is in infants with SMA.  Isis is conducting both Phase 3 studies with agreement from the U.S. Food and Drug Administration (FDA) for special protocol assessments (SPAs).

ISIS-SMNRx is designed to alter the splicing of a closely related gene (SMN2) to increase production of fully functional SMN protein. 

Lynne Parshall, chief operating officer at Isis Pharmaceuticals said:

"CHERISH is the second pivotal Phase 3 study of ISIS-SMNRx we have initiated this year.  The speed at which we have moved this drug from a preclinical development candidate to a late-stage development reflects the successful collaboration we have with Biogen Idec and the support from the SMA community.  It is our hope that this study will build upon the encouraging results we observed in our open-label Phase 2 studies.  Both Phase 3 studies are designed to evaluate the efficacy of ISIS-SMNRx in either infants or children with SMA and to further assess the safety profile in these patients. We are further encouraged by the FDA's agreement on the trial design and planned analysis for both of these Phase 3 studies on ISIS-SMNRx."

Kenneth Hobby, president of Cure SMA  added:

"SMA is a devastating disease that robs people of physical strength by affecting the motor nerve cells in the spinal cord.  SMA is the number one genetic cause of death for infants.  Children with SMA grow weaker as their disease progresses.  Although the genetic cause of SMA is well understood, currently there are no effective drugs available for children with SMA."

"We applaud Isis for investing in and leading drug development efforts for SMA.  We remain hopeful that potential treatments, like ISIS-SMNRx, will be able to provide therapeutic benefit."

CHERISH Phase 3 Study

CHERISH, is a randomized, double-blind, sham-procedure controlled 15 month study in approximately 120 children who are non-ambulatory with SMA between the ages of 2-12.  The study will evaluate the efficacy and safety of a 12 mg dose of ISIS-SMNRx. The primary endpoint will be the 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.

In addition to the current Phase 3 clinical studies ENDEAR and CHERISH, Isis’ partner, Biogen Idec plans to conduct two additional ISIS-SMNRx studies, which could begin in the first half of 2015:

ISIS-SMNRx , Isis, and Biogen Idec

Isis is currently in collaboration with Biogen Idec to develop and potentially commercialize the investigational compound, ISIS-SMNRx, to treat all types of SMA.  Under the terms of the January 2012 agreement, Isis is responsible for global development and Biogen Idec has the option to license the compound until completion of the first successful Phase 2/3 study or the completion of two Phase 2/3 studies.  Isis is conducting two Phase 3 studies with agreement from the FDA for special protocol assessments, or SPAs. A SPA is a written agreement between the FDA and a drug sponsor intended to confirm that the clinical trial protocol is adequate to meet current scientific and regulatory requirements for a potential new drug application.

To learn more about the CHERISH study, visit

To learn more about SMA, visit
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