Isis Pharmaceuticals, Inc. has initiated an open-label extension study, SHINE which 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.

"Both the ENDEAR and CHERISH studies are enrolling on track.  We are pleased to initiate the SHINE study; thus making ISIS-SMNRx available to the patients who have completed one of our phase 3 studies, ENDEAR and CHERISH," said B. Lynne Parshall, chief operating officer at Isis Pharmaceuticals.

"We sincerely appreciate the dedication and support of the SMA community, the patients and their families for participating in and helping us complete the ISIS-SMNRx phase 3 programme. Together with Biogen, we are committed to advancing ISIS-SMNRx toward the market as rapidly as possible. The initiation of the SHINE study supports that commitment and ensures that patients who completed the controlled portion of the phase 3 programme have continued access to ISIS-SMNRx."

Isis and Biogen are evaluating ISIS-SMNRx in a broad clinical programme. Isis is conducting two phase 3 randomized, double-blind, sham-procedure controlled studies of ISIS-SMNRx –ENDEAR and CHERISH. Isis plans to report data from both of these important studies in late 2016 or early 2017. The ENDEAR study is a thirteen-month study in approximately 110 infants diagnosed with SMA. The CHERISH study is a fifteen month study in approximately 120 non-ambulatory children with SMA.

In addition to the phase 3 studies, ENDEAR and CHERISH, ISIS-SMNRx is being evaluated in the following four phase 2 studies: Biogen is evaluating ISIS-SMNRx in an open-label study, NURTURE, in approximately 25 pre-symptomatic newborns who are genetically diagnosed with SMA but presymptomatic.

Biogen is evaluating ISIS-SMNRx in a randomized, double-blind, sham-procedure controlled study, EMBRACE, in 21 patients who do not meet the age and inclusion criteria of ENDEAR and CHERISH studies.

Isis is 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.

Isis acknowledges support from the following organisations for ISIS-SMNRx: Cure SMA, Muscular Dystrophy Association, SMA Foundation and intellectual property licensed from Cold Spring Harbor Laboratory and the University of Massachusetts Medical School.

SMA is a severe genetic disease that affects approximately 30,000 to 35,000 patients in the United States, Europe and Japan. Patients with SMA experience progressive loss of motor function and, in its most severe form, SMA is usually fatal. There are no approved treatments for SMA. The disease is caused by a loss of, or defect in, the survival motor neuron 1 (SMN1) gene, leading to a decrease in the survival motor neuron (SMN) protein. SMN is critical to the health and survival of nerve cells in the spinal cord that are responsible for neuromuscular growth and function. One in 50 people, the equivalent of about six million people in the United States, are carriers of a defective SMN1 gene, which is unable to produce fully functional SMN protein. Carriers experience no symptoms and do not develop the disease. However, when both parents are carriers, there is a one in four chance that their child will have SMA.

Natural history studies have been conducted in patients with SMA. Type I is the most severe form of SMA and most infants with type I SMA die in infancy. In a 2009 paper by Rudnik-Schöneborn, the median age for event-free survival in infants with type I SMA was 6.1 months. In a contemporaneous study published in 2014 by the Pediatric Neuromuscular Clinical Research group (PNCR), the median age for event-free survival in infants with two copies of SMN2 was 10.5 months. The severity of SMA correlates with the amount of SMN protein. 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 walk. Children with type III have a normal lifespan but accumulate life-long physical disabilities as they grow.

ISIS-SMNRx is designed to correct the splicing defect that causes SMA by increasing the production of fully functional SMN protein. The United States Food and Drug Administration granted orphan drug status and fast track designation to ISIS-SMNRx for the treatment of patients with SMA. Isis is currently collaborating with Biogen to develop and potentially commercialize the investigational compound, ISIS-SMNRx, for the treatment of SMA. Under the terms of the January 2012 agreement, Isis is responsible for global development and Biogen has the option to license the compound.