Thank you for the opportunity to speak today. My name is Jack Mitchell, and I am speaking on behalf of the National Center for Health Research. Our research center analyzes scientific and medical data and provides objective health information to patients, providers, and policymakers. We do not accept funding from the drug or medical device industry, so I have no conflicts of interest.
Congress required pediatric-focused safety reviews in accordance with FDASIA. This Advisory Committee meeting is an effort to ensure monitoring by outside experts to ensure that drugs have benefits that outweigh serious risks.
We are particularly concerned about Abilify because of its well established serious side effects of tardive dyskinesia, tremor, muscle stiffness, and sudden cardiac death. Other risks include nausea, somnolence, anxiety, weight gain, high blood sugar, and high cholesterol. Moreover, the impact on a child’s developing brain is unknown because we lack high-quality, long-term research.
The FDA approved Abilify for the treatment of irritability associated with Autistic disorder in patients 6-17-years-old. The drug was approved by the FDA for this indication based on two 8-week, placebo-controlled trials. Because the drug is intended for long-term use but studied for only 8 weeks, the FDA required a post-market study.
The longer-term results indicated no significant difference between Abilify and placebo at week 16 in reducing the symptoms of irritability in pediatric patients who had already maintained a response for the first 12 weeks of Abilify treatment.
There are substantial demographic differences that raise the question about whether Abilify is less safe for girls and less effective for nonwhites. Almost all girls taking Abilify experienced adverse events (91% compared to 43% for boys) and 50% of the nonwhite children on Abilify relapsed, compared to 26% of the white children. Although the number of nonwhite children was very small, that result is still worrisome, especially since the nonwhite children in the placebo arm were much less likely to relapse than the nonwhite children on Abilify and the opposite was true for the white children.
It’s important to remember that all patients who participated in the long-term study had already shown they could tolerate Abilify for at least 12 weeks. For this reason, the reviewer referred to participants in this trial as an “enriched sample” — certainly not typical of all patients. Obviously, adverse events would be higher for patients that weren’t selected on the basis of a previous good response to the drug for 12 weeks.
Clearly the evidence for the effectiveness and safety of Abilify for children with autism and symptoms of irritability is insufficient to outweigh the risks, especially for girls and nonwhite children. We urge the FDA to revise the labeling to state that Abilify has not been proven effective in the long-term for this indication.
Thank you for the opportunity to share our perspective.