Masterstudiengang "Drug Regulatory Affairs"

Master-Thesis

Regulatory Strategy Considerations to Support the Development of a New Estriol Releasing Vaginal Ring Product ***

Larissa Hoffmann (Abschlußjahr: 2022)

Summary
Language: English
Symptoms of vulvovaginal atrophy (VVA) due to decreased estrogenization of vaginal tissue are common in postmenopausal women and cause a significant loss in quality of life (QoL) for the women affected. With the aging population and the modern women’s desire to maintain an active life and sexual activity beyond menopause, the target group and the need for safe and effective treatment is increasing. Still, many women remain untreated due to various reasons: lack of knowledge about VVA, reluctance to discuss symptoms with health care practitioners (HCPs), safety concerns, inconvenience, and inadequate symptom relief from available treatments.
Locally applied estriol (E3) has been widely used in the treatment of symptoms of VVA in the US for many decades through preparations supplied by compounding pharmacies. But up to now, no FDA approved product containing the natural hormone is available on the market for this indication.
This thesis draws on regulatory intelligence information, summarizes considerations and presents development scenarios to answer the following lead question: Is it possible to develop an estriol releasing vaginal ring product for the local treatment of VVA, with the aim to get FDA approval, based on an “aggressive” development strategy with a reduced clinical program?
Authorities are expected to welcome the approach of bringing an FDA registered and therefore properly monitored product to the market. In contrast to the partly outdated high strengths of active ingredient that are used in the currently approved products and the ones available from compounding pharmacies, the proper dose-finding study will ensure, that the lowest effective dose is chosen for the new E3 VR. Furthermore, following approval the E3 VR will be subject to monitoring - not only with respect to pharmacovigilance, but also regarding the manufacturing requirements.
Based on the presented information and especially on the precedent of the Imvexxy estradiol vaginal insert development, it is expected that authorities will enter in discussion with the applicant on in order to determine a streamlined clinical program. The efficacy of estriol in treating symptoms of VVA is widely known and reference can be made to literature data as it is a well-investigated compound. The planned clinical trials will bridge this information to the newly developed estriol releasing vaginal ring product, proving efficacy and safety through the data generated in randomized and controlled clinical trials. Therefore, it seems most likely that the approach is successful.
Nevertheless, close collaboration with the agency should be sought via pre-IND and End-of-Phase-2 meetings, to ensure that a strategy is pursued that in the end satisfies all requirements.
Pages: 35
Annexes: 2, Pages: 8