Advisory Committee Votes Not To Support FDA Approval Of Progesterone Gel For Preterm Birth Prevention

Thanks to our friends over at KeepEmCookin for this post. From their web post, January 21, 2012

Advisory Committee Votes Not To Support FDA Approval Of Progesterone Gel For Preterm Birth Prevention

An advisory committee made up of physicians and public health professionals from around the country voted yesterday 13 to 4 not to support FDA approval of progesterone gel for the prevention of preterm deliveries among women with a short cervical length in the second trimester. The ultimate decision will be made by the FDA’s Division of Reproductive and Urologic Products by February 26.

The Advisory Committee of Reproductive Health Drugs appeared to focus on the difference between study results in U.S. and non-U.S study subjects, an argument presented by an FDA reviewer and an an FDA statistician. Based on FDA analysis of the data (adjusted for maternal age and cervical length) study subjects in the U.S. saw a 2.4 percent reduction in preterm births prior to 33 weeks, whereas non-U.S. subjects saw a reduction of 9.7 percent. The cause of the variation was unclear, though there was speculation about the 28 percent noncompliance rate in the U.S. versus 1.6 percent in non-U.S. regions.

The same data, unadjusted, when analyzed by researchers at NIH and Columbia Laboratories, showed a 44 percent reduction of preterm birth prior to 33 weeks. That randomized and placebo-controlled study (referred to as the PREGNANT study, or Study 302 by the FDA) showed that the progesterone gel was associated with a significant reduction in the risk of preterm birth before 28 weeks and 35 weeks of gestation as well.

The Study 302 results reviewed by the FDA were similar to a recent meta-analysis of five studies on the effects of progesterone gel in preventing preterm birth, where it was shown to reduce the rate of preterm birth prior to 33 weeks by 42 percent.

The Advisory Committee members spoke of other reasons against support for the progesterone gel, including concerns that the drug may only work in a small percentage of women in general, that approval may prevent continued research for alternate solutions, and that a higher standard of scrutiny must be held when a drug manufacturer will be given permission to advertise that a drug performs a certain function. Multiple members of the committee recommended an additional study with a larger sample size, based solely in the U.S.

Frank Condella, President and CEO of Columbia Laboratories, said in a statement yesterday, “We will work with the FDA to address the Advisory Committee’s comments as the Agency finalizes its review of our NDA. We remain confident in the PREGNANT study results that showed the administration of progesterone vaginal gel 8% is a safe and effective treatment for patients at risk for preterm birth due to short uterine cervical length in the mid-trimester of pregnancy. We hope the agency’s final decision will acknowledge the clear unmet medical need in this patient population.”

Also of note, for those familiar with the Makena pricing controversy, a representative from Watson Pharmaceuticals (who would market the drug) stated at the meeting that, if approved, pricing of the progesterone gel as a preterm birth prevention measure would be comparable to its current price under the brand names Crinone and Prochieve, which have been used for more than 10 years to enhance fertility and encourage regular menstrual cycles. These drugs are currently used by some obstetricians off-label for women with a short cervix in the second trimester, which can be discovered incidentally during the 20-week ultrasound.

FDA approval would allow progesterone gel to be more widely used, due to the greater likelihood that insurers will cover its use for this purpose and through the consumer education about short cervix that would result from advertising the progesterone gel.

The Food and Drug Administration’s Division of Reproductive and Urologic Products can be contacted by calling (301) 796-2130 or writing to: Director Scott Monroe, M.D., 5901-B Ammendale Road, Beltsville, MD 20705-1266.