Phase 3 Trial of ISIS-SMNRx Now Open for Children with SMA

Isis Pharmaceuticals has opened a second phase 3 trial to test its "antisense" drug for spinal muscular atrophy in children ages 2 to 12

Article Highlights:
  • ISIS-SMNRx, already being tested in a phase 3 trial in infants with spinal muscular atrophy, will now be tested in a phase 3 trial in children ages 2 to 12 with the disease.
  • ISIS-SMNRx is an "antisense" drug in development by Isis Pharmaceuticals in collaboration with Biogen Idec; it has shown promise in phase 2 studies in infants and children.
  • MDA, while not directly funding this study, has supported laboratory research on antisense as a strategy for treating SMA.
by Margaret Wahl on November 21, 2014 - 10:19am

Update (Dec. 1, 2014): Isis has announced that its partner, Biogen Idec, plans to conduct a phase 2 trial of ISIS-SMNRx in up to 25 presymptomatic newborns genetically predisposed to develop SMA, as well as a phase 2 study of this drug in approximately 20 patients with infantile or childhood-onset SMA who do not meet the inclusion criteria for the current phase 3 studies. These two additional studies could begin in the first half of 2015.

Isis Pharmaceuticals of Carlsbad, Calif., has announced the opening of a large-scale, phase 3 trial of its experimental drug ISIS-SMNRx in children with spinal muscular atrophy (SMA) who are 2 to 12 years old, not able to walk, and experienced their first disease symptoms after 6 months of age.

In August, Isis initiated a phase 3 trial of the same drug in SMA-affected infants age 7 months or younger. This trial is also open and enrolling.

ISIS-SMNRx, in development by Isis in collaboration with Biogen Idec of Cambridge, Mass., is an "antisense"-based drug, designed to change the way cells interpret genetic instructions for a protein called SMN. The full-length, fully functional form of SMN is deficient in the muscle-controlling nerve cells (motor neurons) of the spinal cord in SMA. The goal of treatment with ISIS-SMNRx is to change the way genetic instructions in a gene called SMN2 are "read" by these neurons so that more full-length SMN protein molecules are made.

In October, Isis announced promising results from phase 2 clinical studies of ISIS-SMNRx in infants and in children. On average, infants receiving the drug at either of two dosage levels survived longer and survived without requiring permanent ventilation than did untreated, SMA-affected infants in a recent natural history study. Infants and older children receiving ISIS-SMNRx showed increases in muscle function.

MDA has funded laboratory studies of antisense as a strategy to treat SMA.

About the phase 3 ISIS-SMNRx trial in children ages 2-12

The newly opened trial in SMA-affected children will include approximately 117 children ages 2 to 12, who will be randomly assigned to receive injections of ISIS-SMNRx into the spinal fluid ("intrathecal" injections) or to receive "sham" procedures, involving a needle prick of the skin the area where an injection would have taken place. Neither the parents, participants nor study investigators will know which children received the drug and which did not until it's time to analyze the results.

Participants must

  • have a diagnosis of SMA, with onset of signs of symptoms at later than age 6 months;
  • be 2 to 12 years old at the time of screening;
  • be able to sit independently but have never had the ability to walk independently; and
  • meet other criteria.

Participants must not

  • have respiratory insufficiency requiring invasive ventilation or requiring noninvasive ventilation for greater than six hours per 24 hours at screening;
  • receive the majority of nourishment by feeding tube;
  • have a severe spinal curvature or severe contractures (frozen joints);
  • have an implanted shunt to drain spinal fluid;
  • have received ISIS-SMNRx in any previous study; or
  • have other conditions that may interfere with the interpretation of study results. 

To participate in the phase 3 study of ISIS-SMNRx in children

For details and contact information, see A Study to Assess the Efficacy and Safety of ISIS-SMNRx in Patients with Later-Onset Spinal Muscular Atrophy; or enter NCT02292537 in the search box at See also on the Isis website.

To participate in the phase 3 study of ISIS-SMNRx in infants

For details and contact information, see A Study to Assess the Efficacy and Safety of ISIS-SMNRx in Infants with Spinal Muscular Atrophy; or enter NCT02193074 in the search box at See also on the Isis website.


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