Update on Isis Pharmaceutical's Treatment for Spinal Muscular Atrophy

James Radke

Good news for both children with spinal muscular atrophy (SMA) and investors in Isis Pharmaceuticals.  Today, the company announced it has earned a $2 million milestone payment from Biogen Idec related to the advancement of the ongoing open-label extension study of ISIS-SMNRx in children with SMA. 

The open-label extension study of ISIS-SMNRx was offered to those children with SMA who have completed dosing in Isis' previous studies. 

In the open-lable extension study,  all children with SMA are receiving a 12 mg dose of ISIS-SMNRx every six months for the duration of the study.  

According to Isis, open-label phase 1 and 2 studies have been performed in children with SMA.  In March 2013, they reported ISIS-SMNRx was well tolerated when administered intrathecally as a single dose directly into the spinal fluid. In addition, the children tolerated the intrathecal injection procedure well. Then in September 2013, a follow-up analysis of the single-dose, open-label Phase 1 study observed that most children who received a single dose of 6 mg or 9 mg, continued to show increases in muscle function scores up to 14 months after a single injection of the drug.

In their phase 2 open-label, multiple-dose, dose-escalation study, four dose levels (3, 6, 9, and 12 mg) were studied and  interim results from the 3, 6 and 9 mg cohorts were reported in February 2014 showing that treatment with ISIS-SMNRx was well tolerated and there was a observed dose- and time-dependent increases in HFMSE scores in children treated with multiple doses of ISIS-SMNRx. Children in the 3 mg, 6 mg, and 9 mg cohorts achieved mean increases in HFMSE scores of 1.5, 2.3 and 3.7 points, respectively, nine months following the first dose of ISIS-SMNRx.

Data from the 12 mg cohort have not been reported yet but last November the company reported that 12 mg was the dose they plan to use moving forward with the phase 2 / 3 studies. And today’s announcement that they received a $2 million payment for advancing their open-label extension study with the 12 mg dose, would suggest that dose is the right choice.

Preliminary results from a phase 2 study in infants with SMA receiving 12 mg have also be reported the drug is well tolerated.


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


SMA is a severe genetic disease that affects approximately 30,000-35,000 patients in the United States, Europe and Japan. SMA is caused by a loss of, or defect in, the survival motor neuron 1 (SMN1) gene leading to a decrease in the SMN protein. The severity of SMA is dependent on the amount of SMN protein. Infants with Type I SMA, the most severe form, have a life expectancy of less than two years. Children with Type II have more 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.

For more information about SMA, visit SMA Foundation or Families of SMA.
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