Isis Pharmaceuticals provided an update on both of its ongoing open-label Phase 2 clinical studies of ISIS-SMNRx in infants with spinal muscular atrophy (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.
- 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).
Although the study was not designed to provide evidence of improvement in functional activity, increases in muscle function scores were observed in infants in both cohorts using the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND), a motor assessment test that evaluates muscle strength in infants with SMA. In this test, infants with SMA are examined using 16 different assessments using a scoring scale of 0 to 4 for each assessment (max 64 points). Infants in the PPEP from both cohorts showed mean increases from baseline in CHOP INTEND of 5.4 points at the latest timepoint tested with the seven infants in the 12 mg cohort PPEP showing a mean increase of 8.3 points. Additional endpoints were also examined, including the Hammersmith Infant Neurological Exam Motor Milestones, which showed increased achievements consistent with increases in muscle function scores observed in CHOP INTEND, with nine of the 11 infants in the combined PPEP exhibiting improvements in motor milestones. In infants treated to date, ISIS-SMNRx has been well tolerated with most infants treated with the 12 mg dose. Isis plans to initiate a Phase 3 clinical study in infants with SMA mid-year.
"I am encouraged by the results presented today. These infants tolerated the treatment very well and the data suggest that the drug is reaching the target. The totality of these early data in infants with SMA is encouraging, including the observed trends toward increases in muscle function as measured by CHOP INTEND and Hammersmith Infant Neurological Exam Motor Milestones. Here we have the first drug in the clinic to target the genetic basis of SMA that offers promise of hope for this devastating disease," said Richard Finkel, M.D., chief, division of neurology, department of pediatrics, Nemours Children's Hospital. "SMA is the most common fatal genetic disease of infancy and treatment for these infants is limited to supportive care. Infants with Type I SMA have the most severe form of the disease; they almost never achieve important development milestones such as independent sitting and usually succumb to early death due to progressive weakness of the muscles responsible for breathing and feeding. The CHOP INTEND scale and the Hammersmith Infant Neurological Exam Motor Milestones exam are effective tools for evaluating changes in muscle function in these infants. In general, infants with Type I SMA decline over time in motor function testing, as measured by tests such as the CHOP INTEND and the Hammersmith Infant Motor Milestones."
Results from Phase 2 study in children with SMA were also presented.
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