ISIS-SMNRx to Be Tested in Phase 3 Trial in Infants With SMA

Isis Pharmaceuticals is testing its experimental, antisense-based drug in a phase 3 trial in SMA-affected babies age 7 months or less

Article Highlights:
  • ISIS-SMNRx is an antisense-based drug designed to change the way the SMN2 gene is processed by cells so that full-length, fully functional SMN protein can be made.
  • Improvements in motor function in infants and children in phase 2 studies of ISIS-SMNRx have been seen.
  • The phase 3 trial will be conducted in multiple centers in the U.S., Canada, Europe and Asia Pacific and will include approximately 110 infants with SMA, two-thirds of whom will receive the study drug, and one-third of whom will receive a sham ("fake") procedure.
by Margaret Wahl on August 1, 2014 - 10:24am

California-based Isis Pharmaceuticals has announced the opening of a phase 3 clinical trial of its experimental drug ISIS-SMNRx in infants with spinal muscular atrophy (SMA), a muscle-weakening disease that results from loss of nerve cells in the spinal cord.

Isis announced the start of this new trial in an Aug. 1, 2014, press release.

The drug has shown encouraging results in two earlier (phase 2) studies in infants and children with SMA. Both these earlier studies are now closed to new participants.

Isis plans to start a pivotal trial of ISIS-SMNRx in children (not infants) with SMA later in 2014.


ISIS-SMNRx is based on "antisense" technology, which changes the way genetic information is interpreted by cells. Specifically, this drug changes the way cells read the SMN2 gene, so that functional SMN protein can be made from this gene. The SMN protein is completely or partially missing from the nerve cells of children and adults with SMA.

SMA is caused by mutations in the SMN1 gene, from which full-length, fully working SMN protein is normally produced. However, people with SMA have a variable number of copies of the SMN2 gene, which mostly provides instructions for a short and less than fully functional version of the SMN protein but is capable of providing instructions for full-length SMN protein.

Although MDA is not directly supporting this trial, it has funded the development of this antisense drug.

About the phase 3 trial of ISIS-SMNRx

The phase 3 trial is designed to examine the safety, tolerability and effectiveness of injections of ISIS-SMNRx into the fluid surrounding the spinal cord. (These are known as "intrathecal" injections.)

The investigators are seeking approximately 110 infants with SMA for a multicenter trial lasting 13 months.

Two-thirds of the trial participants will receive ISIS-SMNRx injections, and one-third will receive a "sham" (fake) procedure. The sham group will act as the control group. The sham participants will not receive the study drug and will receive only a superficial (not an intrathecal) injection.

The use of a control group, while difficult for families and investigators, is necessary to determine the benefit versus risk ratio of ISIS-SMNRx. All trial participants will receive the same general care and monitoring, and all participants will be given the opportunity to receive ISIS-SMNRx in an extension study at the end of the phase 3 trial.

Participants in the phase 3 trial of ISIS-SMNRx must:

  • be 7 months old or younger;
  • have a diagnosis of SMA;
  • have two copies of the SMN2 gene;
  • live no more than nine hours away from a study site by ground transportation; and
  • meet additional study criteria.

Study sites are planned for the United States, Canada, Europe and Asia Pacific.

To participate in the phase 3 trial

Contact the study coordinator at the site nearest you. The study sites, with contact information, are listed on the website and on the Isis SMA study website (see below).

For more information

To learn more, see:

Your rating: None Average: 4.3 (7 votes)
MDA cannot respond to questions asked in the comments field. For help with questions, contact your local MDA office or clinic or email See comment policy