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AGRX > SEC Filings for AGRX > Form 8-K on 3-Jan-2017All Recent SEC Filings

Show all filings for AGILE THERAPEUTICS INC



Other Events, Financial Statements and Exhibits

Item 8.01. Other Events.

On January 3, 2017, Agile Therapeutics, Inc. (the "Company") issued a press release announcing top-line results from its Phase 3 SECURE clinical trial of Twirla®, its investigational low-dose combined hormonal contraceptive patch. SECURE was a multicenter, single-arm, open-label, 13-cycle trial that evaluated the safety, efficacy and tolerability of Twirla in 2032 healthy women aged 18 and over at 102 experienced investigative sites across the United States. The Company plans to resubmit its new drug application ("NDA") for Twirla in the first half of 2017 on the basis of the SECURE results and other information relating to the manufacture of Twirla.

The Company will also host a conference call to discuss the top-line results from the SECURE clinical trial on January 3, 2017. A copy of the conference call presentation materials is also attached hereto as Exhibit 99.2.

Top-line data are based on a preliminary analysis of currently available efficacy and safety data, and therefore the reported results, findings and conclusions related to SECURE are subject to change following a comprehensive review of the complete data related to SECURE.

SECURE was conducted to address issues raised by the U.S. Food and Drug Administration ("FDA") in its 2013 Complete Response Letter ("CRL") to the Company. The CRL recommended that the Company conduct a new clinical trial and focused on two key elements: improved clinical trial conduct and demonstration of efficacy as measured by an acceptable Pearl Index and related 95% confidence interval in a representative sample of U.S. women who are seeking hormonal contraception, including elements such as contraceptive user status, age, race, ethnicity, and body mass index ("BMI"). The trial was designed in consultation with the FDA, and comprised a number of stringent trial design elements, including exclusion of treatment cycles not only for use of back-up contraception but also for lack of sexual activity. SECURE had broad entry criteria, placed no limitations on BMI or other demographic factors during enrollment, and enrolled a large and diverse population from the United States in order to allow for efficacy to be assessed across different groups, as requested by the FDA. These entry criteria resulted in the inclusion of a substantial number of women with high BMI, who have frequently been under-represented in past contraceptive studies. The efficacy measure for SECURE was the Pearl Index in an intent to treat population of subjects 35 years of age and under. The FDA also requested inclusion of pre-specified efficacy analyses related to BMI and body weight.

Highlights of the top-line results include:

† Consistent with its broad entry criteria, the SECURE study population was representative of the population of women in the United States with respect to key demographic criteria, including:

† Race (66.9% of subjects were white, 24.3% black and 8.8% other);

† Ethnicity (19.7% were Hispanic, 80.3% non-Hispanic); and

† BMI (39.4% of subjects had a normal baseline weight (BMI of under 25 kg/m2), 25.3% of subjects were overweight (BMI of at least 25 kg/m2 but less than 30 kg/m2), and 35.3% were obese (BMI 30 kg/m2 or more). When classified as obese (BMI 30 kg/m2 or more) or non-obese (BMI less than 30 kg/m2), 35.3% of subjects were obese and 64.7% were non-obese).

† Both new and experienced hormonal contraceptive users were enrolled (9.4% of subjects were new users).

† 51.4% of subjects discontinued prematurely from the study and the loss to follow-up rate was 11.3%, which is in line with loss to follow-up rates observed in previous clinical trials of combined hormonal products and substantially better than the 20% loss to follow-up rate observed in the Company's previous Phase 3 trial.

† The Pearl Index for the overall intent to treat population of subjects 35 years of age and under was 4.80 with an upper-bound of the 95% confidence interval of 6.06. As with all hormonal contraceptive trials, the number of pregnancies included in the Company's calculation of the Pearl Index is subject to review by the FDA as part of its overall review of the NDA for Twirla.

† Consistent with other recent hormonal contraceptive clinical trials, including Ortho Evra® and Quartette®, and the FDA's 2015 meta-analysis on the effect of obesity on the effectiveness of hormonal contraceptives, a relationship between obesity and efficacy was observed among subjects 35 years of age and under:

BMI             BMI      % of Trial                 Upper Bound
Category      (kg/m2)    Population   Pearl Index    of 95% CI
Normal         < 25              39 %        3.03          4.62
Overweight   25 - < 30           25 %        5.36          7.98
Obese*         > 30              35 %        6.42          8.88

Non-Obese*     < 30              65 %        3.94          5.35
Obese*         > 30              35 %        6.42          8.88

*In its 2015 meta-analysis, the FDA examined the effect of obesity on two populations: non-obese (< 30 kg/m2) and obese (> 30 kg/m2). Non-obese includes subjects in the normal and overweight categories.

† The highest Pearl Index for a hormonal contraceptive product approved by the FDA was 3.19 with an upper-bound of the 95% confidence interval of 5.03. As with all products, ultimate approvability of a hormonal contraceptive is based on a risk/benefit assessment of the overall safety and efficacy profile of a product, not only a specific Pearl Index. For hormonal contraceptive trials, the FDA generally evaluates efficacy results of each individual study in the unique context of the study population and trial design.

† Twirla was generally well tolerated and had an overall favorable safety profile, consistent with publicly available information relating to other low-dose combined hormonal products. The most frequent hormone-related adverse events, none of which were experienced by more than 5% of subjects, were generally in line with those events observed in other low dose combined hormonal products and included:

Adverse Event                       (n=2032)
Headache                                 4.3 %
Nausea                                   4.1 %
Breast tenderness/pain/discomfort        2.0 %
Mood swings/changes/depression           2.7 %
Heavy/irregular vaginal bleeding         1.8 %

† The percent of subjects reporting bleeding-related adverse events was low, 1.8%, and only 1.4% of women discontinued for bleeding issues.

† Serious adverse events were observed in 1.7% of subjects. The most common serious adverse events included deep vein thrombosis, pulmonary embolism, gallbladder disease, ectopic pregnancy and depression.

† Overall, patch-related irritation and itching rates were low. Of reported patches worn, 83% had no patch site irritation and 65% had no itching. Generally, reported irritation and itching was mild. Severe itching or irritation were observed in 2.3% and 1.5% of patches worn, respectively.

† The patch adhesion profile was favorable with a low rate of detachment. Of reported patches worn, the range of detachments was 10% in cycle 1 and reduced to 2% by cycle 13.

The Company will also host a conference call to discuss the top-line results from the SECURE clinical trial on January 3, 2017.

Copies of the Company's press release and the conference call presentation materials are attached hereto as Exhibits 99.1 and 99.2, respectively, and are hereby incorporated by reference herein.

Risks Related to the Reported Results of SECURE

The reported results of SECURE are based on top-line data and may ultimately differ from actual results once additional data are received and fully evaluated.

The reported results of SECURE that we have publicly disclosed, and that are discussed herein, consist of top-line data. Top-line data are based on a preliminary analysis of currently available efficacy and safety data, and therefore the reported results, findings and conclusions related to SECURE are subject to change following a comprehensive review of the more extensive data that

we expect to receive related to SECURE. Top-line data are based on important assumptions, estimations, calculations and information currently available to us, and we have not received or had an opportunity to fully and carefully evaluate all of the data related to SECURE. As a result, the top-line results of SECURE that we have reported may differ from future results, or different conclusions or considerations may qualify such results, once additional data have been received and fully evaluated. In addition, third parties, including regulatory agencies, may not accept or agree with our assumptions, estimations, calculations or analyses or may interpret or weigh the importance of data differently, which could impact the potential for approval of Twirla, or if approved, the labeling and commercial value of Twirla and our business in general. If the top-line data that we have reported related to SECURE differ from actual results, our ability to obtain approval for, and commercialize, our products may be harmed, which could harm our business, financial condition, operating results or prospects.

The FDA may disagree with our interpretation of clinical results obtained from SECURE, our results do not guarantee support for a resubmission of our NDA or for regulatory approval, and, even if the SECURE data are deemed to be positive by the FDA, the FDA may disagree with other aspects of the SECURE study and decline to approve Twirla for the proposed indication.

We have reported positive top-line data from SECURE. However, even if we believe that the data from SECURE are positive, the FDA could determine that the data from SECURE were negative or inconclusive or could reach a different conclusion than we did on that same data. Negative or inconclusive results of a clinical trial or difference of opinion could cause the FDA to decline to approve our application or require us to repeat the trial or conduct additional clinical trials prior to obtaining approval for commercialization, and there is no guarantee that additional trials would achieve positive results to the satisfaction of the FDA or that the FDA will agree with our interpretation of the results. Any such determination by the FDA would delay the timing of our commercialization plan for Twirla or prevent its further development, or the further development of our other product candidates, and adversely affect our business operations. Additionally, the FDA may provide review commentary at any time during the resubmission and review process which could delay the review timeline, adversely affect the review process, or even prevent the approval of Twirla, any of which would adversely affect our business. We may not be able to appropriately remedy issues that the FDA may raise in its review of our NDA resubmission, and we may not have sufficient time or financial resources to conduct future activities to remediate issues raised by the FDA.

There is no guarantee that the data obtained from SECURE will be supportive of, or guarantee, an NDA resubmission, or result in our successfully obtaining FDA approval of Twirla in a timely fashion and for a commercially viable indication, if at all. For example, the FDA could determine that the trial did not meet its objectives or the FDA could still have concerns regarding the conduct of the SECURE study, including regarding discontinuance of subjects from the trial. At any future point in time, the FDA could require us to complete further clinical or preclinical trials, or take other actions which could delay or preclude any NDA resubmission or approval of the NDA and could require us to obtain significant additional funding. There is no guarantee such funding would be available to us on favorable terms, if at all, nor is there any guarantee that FDA would consider any additional information complete or sufficient to support approval. If the Twirla NDA is resubmitted, the FDA may hold an advisory committee meeting to obtain committee input on the

safety and efficacy of Twirla. Typically, advisory committees will provide responses to specific questions asked by the FDA, including the committee's view on the approvability of the product candidate under review. Advisory committee decisions are not binding but an adverse decision at the advisory committee may have a negative impact on the regulatory review of Twirla. Additionally, we may choose to engage in the dispute resolution process with the FDA if we do not receive approval, which could extend the timeline for any potential approval.

Further, if we are able to resubmit an NDA for Twirla with the clinical data from SECURE, there is no guarantee that such data will be deemed sufficient by the FDA. While we designed the protocols for SECURE to address the issues raised in the CRL, there is no guarantee that the FDA will deem such protocols or results from the study sufficient to address those issues when they are formally reviewed as a part of an NDA resubmission or to demonstrate safety and efficacy to the satisfaction of the FDA. The FDA has significant discretion in the review process, and we cannot predict whether the FDA will agree with our conclusions regarding the results of the SECURE trial, including whether our . . .

Item 9.01. Financial Statements and Exhibits.

(d)                 Exhibits.

Number                              Description

99.1 Agile Therapeutics, Inc. Press Release dated January 3, 2017.
99.2 Agile Therapeutics, Inc. Presentation on SECURE Top-Line Results

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