DARE-HRT1 is an investigational intravaginal ring (IVR) designed to deliver bio-identical 17β-estradiol and bio-identical progesterone continuously over a 28-day period as part of a hormone therapy regimen. The IVR technology used in DARE-HRT1 was developed by Dr. Robert Langer from the Massachusetts Institute of Technology and Dr. William Crowley from Massachusetts General Hospital and Harvard Medical School. Unlike other vaginal ring technologies, our IVR drug delivery technology is designed to release more than one active ingredient via a solid ethylene vinyl acetate polymer matrix without the need for a membrane or reservoir to contain the active drug or to control the release, allowing for sustained drug delivery.
For some women, hormone therapy is a highly effective treatment for the symptoms associated with menopause, such as hot flashes and vaginal dryness, and may also prevent bone loss and fracture. The delivery of hormone therapy over 28 consecutive days with no daily intervention demonstrated in a Phase 1 clinical study supports DARE-HRT1’s potential to be a first-in-category option offering ease-of-use and continuous dosing to women suffering from menopausal symptoms. There are currently no FDA-approved products that continuously deliver hormone therapy with both estradiol and progesterone together over multiple consecutive weeks.
DARE-HRT1 PHASE 1 CLINICAL TRIAL STUDY DESIGN
The randomized, open-label, three-arm, parallel group Phase 1 study was designed to evaluate the pharmacokinetics (PK) of DARE-HRT1 in approximately 30 healthy, post-menopausal women with intact uteri. The primary objective of the study was to describe the PK parameters of two different dose combinations over 28 days. Secondary objectives of the study were to assess the safety and tolerability of DARE-HRT1 and to compare the systemic exposure of estradiol (the active form for therapeutic hormone therapy purposes), estrone, and progesterone of DARE-HRT1 over 28 days against a daily combination of FDA-approved oral estrogen and oral progesterone products evaluated in the Phase 1 study.
The study was conducted by the company’s wholly owned subsidiary in Australia.
POSITIVE TOPLINE RESULTS OF THE PHASE 1 CLINICAL TRIAL OF DARE-HRT1
Data from the study demonstrate that DARE-HRT1 successfully delivered estradiol and the progesterone over the 28-day evaluation period. The baseline-corrected steady state release of estradiol and progesterone from both the lower (IVR1) and higher (IVR2) dose versions of DARE-HRT1 evaluated in the study demonstrated steady state release levels over 28 days as shown in the table below:
Steady State (Standard Deviation)
|DARE-HRT1 IVR1 (n=10)|
|Estradiol||20.6 (16.8) pg/mL|
|Progesterone||1.32 (0.20) ng/mL|
|DARE-HRT1 IVR2 (n=11)|
|Estradiol||32.5 (9.3) pg/mL|
|Progesterone||2.23 (0.61) ng/mL|
The levels of estradiol released from both the lower and higher dose formulation of DARE-HRT1 evaluated in the study achieved or exceeded the levels that were targeted for hormone therapy. Target levels of estradiol for hormone treatment for either the vasomotor symptoms (VMS) or vaginal symptoms of menopause were established by reviewing PK levels published for FDA-approved products for both the treatment of VMS as well as the genitourinary symptoms of menopause. Based on the estradiol PK data in the DARE-HRT1 Phase 1 study, the results support the potential of DARE-HRT1 as an effective hormone therapy for both VMS and vaginal symptoms associated with menopause. The levels of progesterone released from both versions of DARE-HRT1 evaluated in the study met the objectives of releasing progesterone. Progesterone is used in hormone therapy to reduce the impact of estrogen on nontarget sites, such as the endometrium, to prevent estrogen-induced endometrial hyperplasia.1
In addition, the study treatment was well tolerated with the most common adverse events consistent with other vaginal products. There was only one early discontinuation due to an adverse event, which was found to be unrelated to study treatment or participation, and no serious adverse events were reported. The proportion of participants reporting adverse events was similar across all dose groups, the two DARE-HRT1 groups as well as the group receiving a daily combination of FDA-approved oral estrogen and oral progesterone products, with 89% of adverse events mild in severity and all other adverse events (11%) rated as moderate.
DARE-HRT1 had a high level of acceptability in the study, with over 80% of subjects on the lower and higher dose versions of DARE-HRT1 reporting the IVR as comfortable or very comfortable. Additionally, over 80% of subjects in each IVR dose group stated they were either somewhat or very likely to use the IVR for a women’s health condition or disease if needed.
Following clinical development, we intend to leverage the existing safety and efficacy data on the active ingredients in DARE-HRT1, estradiol and progesterone, to utilize the FDA’s 505(b)(2) pathway to obtain marketing approval of DARE-HRT1 in the U.S.
Read more about the results of the DARE-HRT1 clinical study here.
Menopause is defined as the final menstrual period and is typically confirmed after a woman has missed her period for 12 consecutive months. Most women experience menopause between ages 40 and 58.2 An estimated 45 million women in the U.S. are approaching or in menopause, which results in a decrease in estrogen and other hormones.2,3 Hot flashes, vaginal dryness and loss of bone density are frequently associated with menopause. Night sweats (hot flashes that occur during sleep) often cause sleep disturbance, and vaginal atrophy (the drying and thinning of vaginal tissues) can cause a feeling of vaginal tightness during sex along with pain, burning, or soreness.3 Hence, management of menopausal symptoms can impact quality of life, productivity and health. The North American Menopause Society (NAMS) believes that hormone therapy is the most effective treatment for VMS and the genitourinary syndrome of menopause and observes that a non-oral route may offer advantages over oral routes of administration.3
1 Kuhl, H. (2005) Pharmacology of estrogens and progestogens: influence of different routes of administration. Climacteric, 8:sup1, 3–63. DOI: 10.1080/13697130500148875
2 Menopause 101: A primer for the perimenopausal. NAMS, accessed 25 June 2021. http://www.menopause.org/for-women/menopauseflashes/menopause-symptoms-and-treatments/menopause-101-a-primer-for-the-perimenopausal.
3 The NAMS 2017 Hormone Therapy Position Statement Advisory Panel. The 2017 hormone therapy position statement of The North American Menopause Society. Menopause. 2017 Jul;24(7):728-753. DOI: 10.1097/GME.0000000000000921