Originally published on April 29, 2014
Isis Pharmaceuticals, Inc. today provided an update on both of its ongoing open-label Phase 2 clinical studies of ISIS-SMNRx in infants and children with spinal muscular atrophy (SMA) at the 66th American Academy of Neurology (AAN) meeting in Philadelphia, PA. Isis reports they are on track to initiate Phase 3 study in infants with SMA mid-year and on track to initiate Phase 3 study in children with SMA in the second half of the year.
Results from Phase II Study in Infants with SMA
In the study in infants with SMA, a total of 15 infants have been dosed as of April 7, four infants in the 6 mg cohort and 11 infants in the 12 mg cohort. The 12 mg cohort is continuing to enroll patients.
In the 12 mg cohort:
- Seven infants have received all three induction doses and been evaluated after their last induction dose. These patients constitute the per protocol efficacy population (PPEP).
- Of these seven, five are alive without the need for permanent ventilation. The two infants who have had an event (one death and one permanent ventilation) each experienced the event in connection with pneumonia.
- The median age of the infants in the PPEP in the 12 mg cohort is 9.6 months (calculated using age at event or on April 7 for patients who have not experienced an event).
- Three of the infants not included in the PPEP remain on study and had not yet reached their third induction dose on April 7. One infant died prior to receiving a third induction dose.
In the 6 mg cohort:
- The PPEP in this cohort is comprised of all four infants dosed.
- Two infants are alive without the need for permanent ventilation, one is currently on long-term ventilation and one infant, unfortunately, died due to an accident.
- The median age of the infants in the 6 mg cohort is 14 months (calculated using age at event or on April 7 for patients who did not experience an event).
Results from Phase II Study in Children with SMA
In the study in children with SMA, time and dose-dependent increases in muscle function scores, as measured by the Hammersmith Functional Motor Scale-Expanded (HFMSE), were observed in children treated with multiple-doses of ISIS-SMNRx. Children in the 3 mg, 6 mg and 9 mg cohorts achieved mean increases of 1.5, 2.3 and 3.7 points, respectively nine months following the first dose. Encouraging preliminary results were also observed in two additional functional tests: the six-minute walk test (6MWT), and the upper limb module (ULM) test. In the 6MWT, performed with nine ambulatory children, a mean increase of 22.7 meters was observed at 9 months. In the ULM test, which utilizes a 9 item scale (max score of 18), performed with 10 non-ambulatory children, a mean increase of 2.3 was observed at 9 months. In all children treated with ISIS-SMNRx to date, the drug has been well tolerated at doses as high as 12 mg.
In addition, analysis of cerebral spinal fluid (CSF) samples from children in this study demonstrated dose-dependent increases in SMN protein levels over time in patients treated with ISIS-SMNRx with the maximum effect observed in the 9 mg cohort in which the mean SMN protein level more than doubled by Day 86 from baseline (n=9). Children in the 12 mg cohort have not yet been evaluated. These results are consistent with the increases in SMN protein levels.
For a detailed explanation on this therapeutic approach, visit our research publications page and download our Fall 2013 Compass issue for “The Ins and Outs of Antisense Drugs,” produced in a collaboration between Cure SMA, Biogen, and Isis.