Columbia’s background materials appeared to reflect a different universe of assumptions. "In the efficacy results from Study 302, the U.S. and non-U.S. regions both favored progesterone, although the size of the treatment effect was greater in the non-U.S. regions," the sponsor said. "In contrast, in Study 300 the results for the U.S. subgroup favored progesterone, whereas the non-U.S. results favored placebo. This finding supports the conclusion that the Study 302 regional effect can be attributed to normal variability among subgroups when considering an end point of low incidence; the totality of data from the program suggests beneficial treatment effects in the U.S."
The issues the FDA outlines for advisory committee discussion further indicate the agency’s skepticism about the product’s approvability:
• Has the Applicant provided sufficient information to conclude that progesterone gel reduces the risk of preterm birth in women with a singleton gestation and a short uterine cervical length at midtrimester of pregnancy, given that statistically significant efficacy was not demonstrated in U.S. subjects?
• Do you believe that there is any explanation, based on the data provided in the NDA, for the difference in efficacy results in the U.S. and foreign populations? If yes, do you believe that the explanation could be adequately addressed in labeling so that progesterone gel could be used safely and effectively in the U.S. population?
• Has the Applicant provided sufficient information to conclude that the safety profile for progesterone gel is acceptable for the proposed indication?
Is the overall risk/benefit profile of progesterone gel acceptable to support approval of this product in the U.S. for the proposed indication?
• If not, do you have recommendations as to how efficacy and/or safety could be investigated further in the U.S. population (e.g., a new study)?
Finally, the unmet medical need argument may not be persuasive here due to the approval on Feb. 4, 2011, of KV Pharmaceutical Co.’s Makena (alpha hydroxyprogesterone caproate, or 17P), a synthetic form of progestin given in weekly injections to eligible pregnant women between 16 and 20 weeks’ gestation and continuing until 37 weeks for prevention of preterm birth in women carrying only one fetus who have a history of spontaneous preterm birth with singleton pregnancies.
Makena has drawn the FDA’s ire after launch, however, and in a nod to political pressure regarding the product’s pricing, the agency has not been taking enforcement action against the compounding pharmacies that are still making unapproved versions of the drug at a fraction of the cost, even as KV marshals evidence of their substandard purity and potency.
This coverage is provided courtesy of "The Pink Sheet." This news organization and "The Pink Sheet" are owned by Elsevier.