SMA: Interim Results Look Promising for SMN-Raising Drug

Interim results of a phase 2 clinical trial to test multiple doses of the experimental drug ISIS-SMNRx in infants with spinal muscular atrophy (SMA) suggest that the drug is well-tolerated and may prolong ventilator-free survival.

California-based biotechnology company Isis Pharmaceuticals announced these early findings from an ongoing trial in a Feb. 21, 2014, press release. The company developed ISIS-SMNRx in collaboration with MDA-supported Adrian Krainer at Cold Spring Harbor Laboratory in New York state.

The drug is designed to change the way cells read genetic instructions for the SMN protein, which is deficient in patients with SMA, with the goal of raising the level of full-length, fully functional SMN.

Ventilator-free survival reported in four infants

In the ongoing phase 2 trial, doses of either 6 milligrams or 12 milligrams are being administered into the fluid surrounding the spinal cord on days 1, 15 and 85 of the study.

There are four infants in the 6-milligram dosage group, all of whom have been in the study for more than six months and have received all three of their scheduled doses of ISIS-SMNRx. The infants are now approximately 9.6 to 16 months old, with an average age of 12.5 months.

All four are alive and none has required permanent ventilation assistance. A recent study of the natural history of infants with SMA found that half had died or been put on permanent ventilation by about 10 months of age, suggesting that the four infants in the 6-milligram group who have reached an average age of 12.5 months without permanent ventilation are doing better than the natural history studied would have predicted.

"Even though these are interim results from a small number of infants, we are encouraged by the observation that all four infants in the 6-milligram cohort are still alive and not on permanent ventilation," said C. Frank Bennett, senior vice president of research at Isis. "These interim results, while early, provide support for advancing ISIS-SMNRx into a phase 3 study in infants."

Webcast available

A Feb. 24 Isis webcast presented details of the interim phase 2 results and is available for replay. Isis plans to release more data from this study at the upcoming American Academy of Neurology meeting in April.

Study remains open

The phase 2 study remains open to infants with SMA who are 210 days old or younger and meet study criteria. For details, see Study to Assess the Safety and Pharmacokinetics of ISIS-SMNRx in Infants with SMA or enter NCT01839656 into the search box at

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