Isis Pharmaceuticals, Inc. has dosed first child in the 12 mg group of ongoing phase II study evaluating ISIS-SMNRx in children with spinal muscular atrophy (SMA). Isis also announced that the first child was dosed in an open–label extension study, which is being offered to those children with SMA who have completed dosing in Isis' previous studies.

Isis will receive two milestone payments totaling $7.3 million for advancements in these studies. The dosing in the phase II study in infants with SMA is also being extended. Under the extension, infants who have completed the three initially scheduled study doses will be eligible to receive an additional dose of 12 mg. The first infant in the study has received a fourth dose of ISIS-SMNRx approximately six months after the three initial doses were completed. For this achievement, Isis will receive a $2 million milestone payment from Biogen Idec.

"The progress we and Biogen Idec have made on ISIS-SMNRx exemplifies the value of our strategic alliance and the benefit of working closely together with combined expertise to support rapid development. We also benefit financially. Including the more than $9 million announced today, we will have received more than $45 million in upfront fees, milestone and other payments from Biogen Idec as ISIS-SMNRx has advanced. This year we anticipate making significant progress in this and other programs we are working on with the Biogen Idec team," said B Lynne Parshall, chief operating officer at Isis. "The ongoing multiple-dose studies in infants with Type I SMA and in children with Type II and Type III SMA are progressing, and we look forward to sharing the top-line data from these studies this quarter and more detailed results at the American Academy of Neurology meeting in April."

ISIS-SMNRx is currently being evaluated in an open-label, multiple-dose, dose-escalation phase II study in children with SMA with Type II and Type III SMA. In this study, which is designed to assess the safety, tolerability and pharmacokinetic profile of ISIS-SMNRx, all children have completed dosing in the initial three cohorts (doses of 3 mg, 6 mg and 9 mg) and the first child has been dosed in the 12 mg cohort.  The new open-label extension study is designed to provide a single additional dose of 12 mg and is open to the more than 50 children with SMA who have completed dosing with ISIS-SMNRx in other studies. Children with Type II or Type III SMA between the ages of 2 -15 may enroll in the 12 mg dose cohort of the open-label, multiple-dose phase II study. The study is being conducted at centres in the United States.

ISIS-SMNRx is also being evaluated in an open-label, multiple-dose, dose-escalation phase II study in infants with Type I SMA. In the ongoing phase II study, all infants from the 6 mg dose cohort have completed the three initially scheduled doses and, under the amended protocol, are eligible to receive an additional 12 mg dose six months after their initial three scheduled doses. Isis announced late in 2013 that the study was expanded to enroll up to 20 infants and that the first infant was dosed in the 12 mg dose cohort. Infants from the 12 mg dose cohort will also be eligible to receive an additional 12 mg dose six months after they have completed the initial three scheduled doses. Infants may enroll in the phase II study if they are between the ages of three weeks and seven months, live in close proximity to a study site and pass screening evaluations conducted at study sites. The study is being conducted at centres in the United States and Canada.

ISIS-SMNRx is designed to alter the splicing of a closely related gene (SMN2) to increase 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 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 II/III study.

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

Biogen Idec and Isis have established four collaborations focused on leveraging antisense technology to advance the treatment of neurological and neuromuscular disorders. This alliance combines Isis's expertise in antisense technology to evaluate potential neurological targets and discover antisense drugs with Biogen Idec's capability to develop therapies for neurological disorders. Isis is primarily responsible for drug discovery and early development of antisense therapies. Biogen Idec has the option to license each antisense program at a particular stage in development.  Current development-stage programs include antisense drugs to treat SMA, ISIS-SMNRx, and myotonic dystrophy type 1, ISIS-DMPKRx.

Isis is exploiting its leadership position in antisense technology to discover and develop novel drugs for its product pipeline and for its partners.