On February 27, 2012, Watson Pharmaceuticals, Inc. and Columbia Laboratories, Inc. announced that the FDA rejected a vaginal gel for use in the reduction of the risk of premature birth (delivery less than 37 weeks gestation). The FDA said that the data presented did not reach the level of statistical significance necessary to support approval of the progesterone vaginal gel 8% and that additional clinical studies are necessary.

In January, an FDA advisory panel recommended that the FDA reject the drug because the data was not strong enough to show that it worked.

Analysis:

Data from the PREGNANT study was submitted to the FDA, which showed that women with a short uterine cervical length (measured by trans-vaginal ultrasound) who underwent treatment with progesterone vaginal gel 8% had a significantly lower risk of preterm birth compared to those treated with placebo. The most frequent adverse events in women treated with progesterone vaginal gel 8% were high-risk pregnancy complications, including premature baby, uterine contractions abnormal, and premature labor. Cervical disorder, nausea, headache, and vulvo vaginal mycotic infection were also reported.

Progesterone gel 8% was first FDA approved for vaginal use in 1997 for progesterone supplementation or replacement as part of an Assisted Reproductive Technology (ART) treatment for infertile women with progesterone deficiency. It is marketed under the brand names Prochieve (available in 4% and 8% concentrations)?and Crinone. It has received FDA approval for infertility and secondary amenorrhea. However, progesterone gel 8% has not yet received approval in any country for once daily administration for the reduction of risk of preterm birth in women with a singleton gestation and a short uterine cervical length in the mid-trimester of pregnancy.

Makena (hydroxyprogesterone caproate injection) is a similar drug, which was FDA approved on February 3, 2011 and is marketed by K-V Pharmaceutical Co. It is indicated for the reduction of the risk of certain preterm births in women who have had at least one prior preterm birth. Currently no other drugs are FDA approved for women with a short cervix, who may be at a higher risk of preterm birth.

Paul M. Bisaro, Watson President and CEO, said, ?We have formally requested an end of review meeting with FDA to determine if a viable path forward can be established for this application. We believe that there is a significant unmet medical need for a safe and effective treatment of patients at risk for preterm birth which affects approximately one-in-eight live-born infants in the U.S.?

Using data from AERS, from 01/01/2004 to 9/30/2011, aggregated and standardized by the AdverseEvent RxFilter process, we identified 47 patients who experienced a serious adverse event where Crinone was identified as a suspect drug causing the event and 21 patients who experienced a serious adverse event where Crinone was identified as the primary suspect. The most commonly reported side effects were drug exposure during pregnancy, abortion spontaneous, and maternal drugs affecting fetus. We identified 4 hospitalizations and 3 deaths where Crinone was identified as the primary suspect.

We identified 73 patients who experienced a serious adverse event where Makena was identified as a suspect drug causing the event and 57 patients who experienced a serious adverse event where Makena was identified as the primary suspect. The most commonly reported side effects were premature baby, maternal exposure during pregnancy, and premature labor. We identified 15 hospitalizations and 9 deaths where Makena was identified as the primary suspect.