Just a few months after telling TherapeuticsMD that its treatment for vaginal pain during sexual intercourse lacked data on safety, the FDA has changed its mind.
In May, the agency said it wanted 12-month safety data for TX-004HR before it would accept a regulatory filing for the estradiol vaginal softgel product, rather than the 12-week data submitted by the company. Now, it seems it has reconsidered its earlier position and won’t ask for a lengthy new trial to be undertaken.
The main point of concern for the FDA was endometrial safety, a perennial issue with estradiol products, but the company says it persuaded the regulator at a face-to-face meeting ahead of the weekend that it could press on with a resubmission within the next few weeks.
TherapeuticsMD was incensed by the initial rejection of TX-004HR in May, claiming that the request for the long-term study came out of left field and followed “numerous discussions with the FDA regarding the safety and efficacy design of the trial to support approval.” Now, it says the agency has agreed to waive the preapproval study, as long as the company agrees to postapproval observational study to monitor safety.
The biotech insists TX-004HR was specifically designed to be placed in the lower third of the vagina, decreasing the likelihood of stimulating endometrial tissue compared to other estrogen replacement therapy (ERT) products.
The change of heart could also reflect an elevation in female health as a priority at the FDA, which published a “roadmap” last year with the aim of speeding up the development and launch of products and technology that benefit women. It also chimes with a light touch on regulation under the regime of current Commissioner Scott Gottlieb, M.D., who has said he wants to accelerate drug approvals and do away with regulatory red tape.
The biotech has been bullish on its chances of changing the FDA’s mind, saying in an investor update last month that it was still anticipating a November 2017 resubmission and a launch in 2018.
“We appreciate the hard work and collaborative effort by the
TherapeuticsMD is trying to tap into the market for female sexual health products, which has been spearheaded in the U.S. by Sprout Pharma (now part of Valeant) with Addyi (flibanserin), approved two years ago to treat low sexual desire in premenopausal women but thus far failing to make much headway commercially.
TX-004HR is intended for use in a different and arguably less controversial population: postmenopausal women who experience pain on intercourse caused by a thinning of the cells lining the vaginal walls resulting from declining estrogen levels. It is designed to minimize systemic exposure to estradiol, which has been linked to endometrial cancer, by using a lower dose than rival ERTs such as Pfizer’s Premarin cream and Allergan’s Estrace.
A second product called TX-001HR, which combines estradiol with progesterone, is expected to be filed before the end of the year for moderate-to-severe vasomotor symptoms due to menopause after TherapeuticsMD reported a positive phase 3 trial. It could also be approved before the end of 2018, says the company.