FDA advisory committee: Cethromycin safe but not proven effective

The FDA’s Anti-Infective Drugs Advisory Committee voted that cethromycin is safe but not effective for the outpatient treatment of mild-to-moderate community-acquired pneumonia.

Oral cethromycin (Restanza, Advanced Life Sciences Holdings) was compared with clarithromycin in two phase-3 trials. The advisory committee made its recommendations based on these results.

When asked if the trial results demonstrated a positive safety profile for cethromycin, 11 committee members voted positively, three voted negatively and one abstained. When asked if the trial results demonstrated sufficient efficacy for cethromycin, three members voted positively, 11 voted negatively and one abstained.

James Floyd, MD, a health researcher at Public Citizen, a non-profit public health advocacy group, said various factors may have affected the results. Speaking to the advisory committee, Floyd said prior administration of antibiotics, loss to follow-up, premature discontinuation of treatment, use of non-study antibiotics and intercurrent illness among study participants should call into question the validity of the study results. He also said that the treatment difference in one of the trials did not exclude a margin of 10%, and that the possibility of hepatotoxicity induced by cethromycin may be cause for concern.

“For a drug that may potentially be hepatotoxic and offers no convenience advantage, it becomes difficult to justify tolerating anything less than superiority over another effective antibiotic, let alone questionable non-inferiority findings,” Floyd said. “If additional non-inferiority trials are conducted, they must be designed far more rigorously.”