The FDA has denied approval for a vaginal progesterone gel meant to prevent preterm birth, saying that the data were lacking to prove the gel is more effective than placebo.

The 8% progesterone gel was developed by Watson Pharmaceuticals and Columbia Laboratories, which are seeking marketing approval for the gel to prevent premature labor in women with a shorter-than-normal cervix (≤3 cm at 24 weeks’ gestation).

Short cervix length is a well-known risk factor for preterm births.

In letter sent to Watson, the FDA said the companies’ trial failed to meet statistical significance and that additional clinical studies would be necessary before the gel could be approved.

The rejection was expected, given that an FDA advisory panel in January voted 13-4 against recommending approval for the gel.

The decision was based on Columbia Laboratories’ 10-country study, which randomized 465 pregnant women with sonographically confirmed short cervices to the 8% progesterone gel or to a placebo gel, which women were to self-administer once a day in the morning.

The primary endpoint was delivery before 33 weeks of gestation. Secondary endpoints included delivery before weeks 28, 35, and 37 as well as adverse events for mothers and infants.

Nearly 9% of the women treated with the gel gave birth before 33 gestational weeks, compared with 15.2% of those in a placebo group (P=0.02).

But the gel only reached statistical significance for preventing births at 33 weeks; it did not appear statistically significantly better at preventing preterm birth before 27 weeks, 34 weeks, or 36 weeks.

There were no differences in adverse events between the progesterone gel and the placebo groups.

The panelists said while the drug was safe, it did not appear to be effective.

Paul Bisaro, president and CEO of Watson, said the company would continue to work with the FDA on a “viable path forward” for the gel.

“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,” Bisaro said in a statement issued Monday.

Progesterone gel has not been approved in any country for reduction of the risk of preterm birth. There is one drug, hydroxyprogesterone caproate (Makena), approved to prevent preterm birth in women with a history of preterm birth.

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By Emily P. Walker, Washington Correspondent, MedPage Today