Shares of Agile Therapeutics Inc. (NASDAQ:AGRX) trebled Thursday, rising 223.8% to $1.20 at the market's close following a near-unanimous FDA adcom vote the day before supporting approval for the company's transdermal contraceptive patch, Twirla (levonorgestrel/ethinyl estradiol). Called a "historic upset after extremely discouraging briefing docs" by H.C. Wainwright analyst Oren Livnat, the decision centered the benefits of greater contraceptive choice for women over concerns around Twirla's efficacy, highlighting a gap between the agency's view and that of its advisers. Moving ahead, Agile CEO Al Altomari told BioWorld that "mentally, we're ready to go to market." (See BioWorld, Oct. 31, 2019.)
Now, with Twirla's Nov. 16 PDUFA date fast approaching, what lies ahead for the Princeton, N.J.-based company is rebuilding in preparation for a potential product approval. It's going to take some time, Altomari said, projecting a launch for the patch in the second half of 2020. "While we have the plan, we don't have the people and the processes set up," he said. Furthermore, he acknowledged, the company isn't across the goal line yet with respect to approval. But it's certainly making moves to prepare for a positive outcome.
With $18.4 million in cash as of Sept. 30, Agile should be able to fund operations through the end of the first quarter of next year, according to Altomari. That money will, in part, fund an acceleration of its commercial activities, such as recently restarted manufacturing development at Corium Inc., a Menlo Park, Calif.-based manufacturer of transdermal products. Twirla is currently working with Corium to complete manufacturing development and process improvements and plans to start pre-validation when that work is complete, with the goal of completely validating the product's commercial manufacturing process in the second half of 2020.
Agile's management is also working with managed care and patient payers to gain market access for Twirla in the first quarter of 2020, ahead of plans to hire and train an initial sales team, which it estimates will be in the range of 50 to 90 people.
An ability to focus on such preparations with a modicum of confidence that the product may be approved, should the agency follow the adcom's advice, is no doubt a welcome change for investors. Shares in the company spiraled down to a 45-cent close just a day before the meeting as the tone of FDA briefing documents suggested the product's third review could be the end of its road. (See BioWorld, Oct. 29, 2019.)
Efficacy results weren't impressive for the combined hormonal contraceptive (CHC), especially in obese women, a subpopulation the FDA has said should be studied in trials of contraceptives, the agency said. That point of view was evidenced by the results of Study 23, a phase III, open-label, single-arm trial evaluating Twirla's effectiveness, safety, cycle control, treatment compliance and transdermal adhesion. Intended to resolve problems identified in previous trials of the weekly patch, Study 23 gave Twirla a Pearl Index (PI) score of 5.83. (The PI reports the pregnancy rate per 100 women-years of drug exposure.)
"Fortunately, the panel looked past the FDA's admittedly arbitrary Pearl Index efficacy hurdle, and looked past the FDA's alarmist safety concerns for which we saw no real indicator of above-normal risk and delivered what has to be one of the biggest adcom upsets," Livnat said.
Though the Nov. 16 PDUFA date is near, Livnat suggested the complexity of the decision ahead of it after the Bone, Reproductive, and Urologic Drugs Advisory Committee's meeting Wednesday might mean the FDA meeting that date is "a little optimistic."
That could give the agency and Agile some extra breathing room to arrive at agreement on the best label for the product, one that either speaks broadly to the effect of high body-mass index on contraceptives in general, or one that is more restrictive, including a limitation of use statement. Meanwhile, embracing the role of a gracious winner after the proceeding, Altomari said his team appreciated the agency having set up the adcom to support an open dialogue. "They clearly had points of view and so did we," he said. "As much as the FDA needed the advice, we needed the advice, too," he added.