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# TherapeuticsMD Getting Safety Data for Estradiol Cap
- URL: https://www.fdaweb.com/therapeuticsmd-getting-safety-data-for-estradiol-cap/
- Published: 2017-08-11T12:00:00.000Z
- Updated: 2026-09-14T22:40:40.000Z
- Author: David McFarland
- Tags: Drugs, #legacy-id-D5139368

TherapeuticsMD says it will submit additional endometrial safety information to address the only approvability issue raised in a May-issued complete response letter (CRL) on an NDA for TX-004HR, the company’s investigational applicator-free estradiol vaginal softgel capsule for treating moderate-to-severe vaginal pain during sexual intercourse (dyspareunia), a symptom of vulvar and vaginal atrophy (VVA) due to menopause.

The agency’s CRL raised concern about a lack of long-term endometrial safety data beyond the 12 weeks studied in the pivotal phase 3 Rejoice Trial, the company says. “No cases of endometrial hyperplasia were observed in the Rejoice Trial at the end of week 12 for all the doses studied and included in the NDA,” it says. “The CRL did not identify any issues related to the efficacy of TX-004HR and did not identify any approvability issues related to chemistry, manufacturing, and controls.

  
TherapeuticsMD says it has received a formal general advice letter from FDA stating that an initial review of preliminary information has been completed and requesting that it submit additional endometrial safety information to the NDA on or before 9/18, including safety data from a very large, observational study of long-term, real-world users of vaginal estrogens that is pending publication. “The FDA requested approximately six weeks to perform a comprehensive review of these data and has requested a meeting with the company to discuss the outcome of this review,” it says. “A tentative meeting date of 11/3 has been set by the agency. At this meeting, the company expects to learn if this additional endometrial safety data addresses the lack of long-term safety identified in the CRL. The company currently plans to re-submit the NDA for TX-004HR shortly thereafter.”