FDA advisory committee splits vote on artesunate rectal suppositories

The FDA’s Advisory Committee on Anti-Infective Drugs voted to recommend a 100 mg single-dose artesunate rectal suppository to treat patients ages 6 or younger who have suspected malaria, are unable to take oral medications and lack access to empiric IV therapy, but the panel said more data are needed before they could recommend a 400 mg formulation to treat patients older than 6 years.

The committee’s recommendations followed a study of 12,068 people in Bangladesh, Ghana and Tanzania. The suppository was administered to 6,072 patients and placebo was administered to 5,996 patients. The primary endpoints were mortality or permanent disability within seven to 30 days.

There were 154 fatalities in the artesunate cohort and 177 fatalities in the placebo cohort (2.5% vs. 3.0%, P=0.1). Pre-referral rectal artesunate significantly reduced death or permanent disability (RR, 0.49; 95% CI, 0.32-0.77), among patients who were unable to reach a clinic for more than six hours, according to results of the study.

Several panel members agreed there was a lack of sufficient safety data and a lack of data on patients for whom both formulations would be most effective. However, the high mortality rate from malaria among young children in rural areas of developing countries prompted the committee to overlook potential shortcomings in the study.

Committee member Archana Chatterjee, MD, PhD, of the pediatric infectious disease department at Creighton University Medical Center, said that efficacy of the suppository was demonstrated in children but not necessarily in adults.

“Perhaps we would be viewing this situation differently if it wasn’t such a dire disease in the third world,” she said. “But in this case, we should not let the perfect be the enemy of the good.” – by Rob Volansky