FDA Rejects Agile's Contraceptive Patch Twirla For a Second Time

Shares of Agile Therapeutics plunged more than 62 percent in early trading after the company announced this morning the U.S. Food and Drug Administration rejected its low-dose hormonal contraceptive patch called Twirla.

The FDA was set to review Agile’s New Drug Application on Dec. 26, but delivered an early and unwelcome holiday present in the form of a Complete Response Letter a few days early. In the CRL, the FDA identified a number of concerns with Twirla, including third-party manufacturing issues by Corium International Inc. and deficiencies relating to quality adhesion test methods. Perhaps more critically, the FDA CRL questions the in vivo adhesion properties of Twirla and their potential relationship to the SECURE Phase III clinical trial results, Agile said in its announcement. Additionally, the CRL recommends that Agile address the implications of clinical trial subject patch compliance and the withdrawal and dropout rates. Citing the CRL, Agile said the FDA determined that the regulatory agency cannot approve the NDA in its present form.

There were no safety issues addressed by the FDA.

Agile said it submitted an amendment to its NDA in response to issues related to quality adhesion test methods cited in the CRL. Additionally, Agile said that its third-party manufacturer Corium provided responses to FDA "addressing each of the observations made during the FDA’s facility inspection" on Nov. 20 and Dec. 1. Agile noted that the CRL does acknowledge the receipt of the amendment, but noted that the amendment was not reviewed prior to the FDA rejection of Twirla.

Al Altomari, chairman and chief executive officer of Agile Therapeutics, said the company intends to request a meeting with the FDA to discuss the CRL and seek to resolve the issues it raised.

This is the second time the FDA rejected Twirla. In 2013, the regulatory agency rejected the company’s NDA and called for additional clinical testing. In July of this year, Agile resubmitted the NDA with efficacy and safety data from a new Phase III clinical trial.

Twirla is a combined hormonal contraceptive (CHC) patch that contains the active ingredients ethinyl estradiol (EE), which is a type of estrogen and levonorgestrel (LNG), a type of progestin. The contraceptive is designed to be applied once weekly for three weeks, followed by a week without a patch.

Altomari said the company is disappointed in the FDA rejection. He said the company will work with the FDA to "address the points raised in the CRL as quickly as possible."

In its last quarterly announcement, Agile reported $43.8 million in cash and cash equivalents on hand. The company said at the time that the available cash would be enough to carry the company forward through the second quarter of 2018. The company noted at the time that Twirla figured prominently into its business plan. It is unknown how a second rejection of the drug will impact company guidance. Agile will hold a conference call this morning to address the CRL and likely how that will impact its finances.