FDA provides guidance on development pathway for testosterone therapy for women

A female-specific testosterone therapy may soon be entering clinical development, according to a news release from Aviva Bio.¹

In a recent type B meeting with the FDA, the agency provided guidance to Aviva Bio regarding the requirements necessary for development of AVA-291 (d3-T), a novel testosterone formulation for women.

“For decades, testosterone therapy for women has depended on repurposed male formulations, rather than drugs designed with women’s biology and safety considerations in mind,” explained Judith A. Boice, PhD, CEO of Aviva Bio, in the news release from the company.¹ “Our FDA feedback reinforces the need for a new standard—one anchored in safety, enabled by molecular precision, and developed with regulatory clarity from the start.”

According to Aviva Bio, AVA-291 is a “next-generation testosterone designed to retain [testosterone]’s androgen activity while resisting aromatization.” The ability of AVA-291 to resist aromatization is notable, given that aromatization of testosterone locally in breast tissue has been linked to an increased risk of breast cancer. This safety concern has historically limited the development of a testosterone formulation for women, Aviva noted.

Data supporting the differentiated safety profile of AVA-291 will be presented at the American Association for Cancer Research (AACR) Annual Meeting in April 2026, showing that AVA-291 (d3-T) is associated with an approximately 1,000-fold lower potential to stimulate breast cancer cell proliferation compared with ordinary testosterone.

“The data we are presenting at AACR provides mechanistic evidence that AVA-291 (d3-T) has a reduced risk of exacerbating breast cancer compared with ordinary [testosterone],” said Bradford C. Sippy, CTO of Aviva Bio, in the news release.¹ “This builds on our prior work showing that AVA-291 is resistant to aromatization and highlights the potential clinically differentiated profile.”

Thus, the development program for AVA-291 will focus on advancing the therapy across multiple indications in both women’s and men’s health “where androgen signaling plays a clinically meaningful role,” but aromatization “limits [testosterone’s] therapeutic potential.” AVA-291’s differentiated formulation may provide a useful alternative to ordinary testosterone in these situations, which may include use as a hormone replacement therapy in menopausal women, for men on testosterone therapy who develop gynecomastia, for addressing muscle loss and/or low-libido in patients on GLP-1 therapy, and in the treatment of ER-positive breast cancer.

According to Aviva, AVA-291 shares similar physical properties to testosterone and can be substituted in any current testosterone formulation.

Boice explained in a prior news release,² “d3-T is a novel, structurally identical form of testosterone where select hydrogen molecules have been substituted with deuterium. This small change creates a significant breakthrough.”

Aviva also announced in the prior release that the company is planning to initiate a phase 1 trial of AVA-291 in early 2026.

REFERENCES

1. Aviva Bio announces FDA guidance on development pathway for women’s testosterone therapy and new evidence of a reduced risk of breast cancer cell proliferation for AVA-291. News release. Aviva Bio. January 26, 2026. Accessed January 26, 2026. https://www.businesswire.com/news/home/20260126103179/en/Aviva-Bio-Announces-FDA-Guidance-on-Development-Pathway-for-Womens-Testosterone-Therapy-and-New-Evidence-of-a-Reduced-Risk-of-Breast-Cancer-Cell-Proliferation-for-AVA-291

2. Aviva Biopharm Inc. unveils groundbreaking pre-clinical data on d3-T, a first-in-class testosterone therapy for women at ENDO 2025. News release. Aviva Bio. July 14, 2025. Accessed January 26, 2026. https://aviva-bio.com/wp-content/uploads/2025/08/Aviva-Bio-ENDO-Press-Release-7.14.25.pdf