FDA rejection sets back TherapeuticsMD

Dive Brief:

  • The Food and Drug Administration has issued a complete response letter, dashing TherapeuticsMD's hopes for approval of its estradiol vaginal softgel capsule for moderate-to-severe vaginal pain during sexual intercourse (dyspareunia).
  • The CRL has asked for 12-month endometrial safety data for TX-004HR; only 12 weeks' worth of data is available at the moment from the pivotal Phase 3 REJOICE trial. The FDA hasn't raised any concerns over efficacy or manufacturing.
  • TherapeuticsMD's stock sank yesterday, falling to $3.52 at its lowest point and closing down over 10% at $4.18.

Dive Insight:

TherapeuticsMD's lead drug TX-004HR, with the conditionally-approved trade name Yuvvexy, has just received a major knockback, with a request for long-term endometrial safety data that the company claims it hadn't been asked for in the first place. TherapeuticsMD first gave a hint that news from the FDA for the product, 17β-estradiol formulated in a VagiCap vaginal softgel, was on its way on April 19.

"While we are disappointed that the NDA for TX-004HR was not approved at this time and respectfully disagree with the FDA’s decision, we believe there are multiple paths forward to address the concerns raised by the FDA. The FDA has encouraged us to request a meeting to discuss our path forward and we intend to meet with the FDA as quickly as possible," said TherapeuticsMD CEO Robert G. Finizio.

It's not clear what the company's next step will be, as a 12-month trial will be expensive, and will delay the launch of the drug into an already crowded market that includes both generic and originator product competitors. Analysts at Jefferies note the positive point that the FDA hasn't cited any concerns for efficacy, manufacturing or 12-week safety, and suggest that the 12-month data may be able to be collected in a post-launch Phase IV trial, though this will depend on the company's meeting with the FDA.

"If [the] FDA agrees to approve [TX-004HR] with a post-approval study we expect it could obtain a class label with boxed warning. Concerns about LT endometrial safety data may be addressable through biopsy +/- transvaginal ultrasounds as part of a larger study, but FDA guidance is not entirely explicit on this topic," says Matthew J Andres, Jefferies equity analyst, in a note to investors.

TherapeuticsMD's remaining drugs are still a while off launch, and all target the same well-supplied market. The next product in the pipeline is TX-001HR, a "bio-identical" oral combination of 17ß-estradiol and progesterone to treat vasomotor systems related to menopause, which the company "believes to be the first and only combination drug product candidate designed to replace the 17ß-estradiol and progesterone hormones the ovary has nearly stopped producing." Topline data presented in early April was mixed, with statistically significant and clinically meaningful reductions in the frequency and severity of hot flashes compared to placebo at weeks four and 12, at two of the four doses tested.

"We are also continuing to prepare the NDA for TX-001HR, our investigational oral bio-identical combination of estradiol and progesterone, and anticipate that we will submit that NDA to the FDA as early as the third quarter of 2017," Finizio added.

Andrews adds that the lack of FDA CMC concerns with Catalent's Florida manufacturing facility used for TX-004HR, and the lack of other safety concerns, both bode well for TX-001HR.

Enrollment in TherapeuticsMD's Phase 3 Spry trial of its oral progesterone candidate, TX-002HR, was temporarily suspended in July 2014, and stopped in order to update the Phase 3 protocol, as confirmed in the company's 2016 annual report and Form-10k published in February 2017. Development is on hold to allow focus on other candidates. THX-006HR, a transdermal combination estradiol and progesterone, is expected to move into Phase 1 during 2017, and THX-003HR, an oral estradiol, has ceased development.

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Filed Under: Regulatory / Compliance
Top image credit: Dan Moyle