Dare Bioscience, Inc, a biopharmaceutical company committed to advancing innovative products for women’s health innovation, announced positive topline results from the phase 1 study evaluating the pharmacokinetics (PK), safety, and exploratory efficacy of DARE-PDM1. DARE-PDM1 is an investigational product designed to deliver diclofenac, a nonsteroidal anti-inflammatory drug (NSAID), vaginally via the company’s proprietary hydrogel to treat primary dysmenorrhea, which is defined as painful menstruation in women with normal pelvic anatomy. DARE-PDM1 has the potential to be a first-in-category product, delivering diclofenac in a convenient vaginal format that may extend the duration of pain relief and reduce the risks associated with the oral delivery of NSAIDs.
The DARE-PDM1 phase 1 study, DARE-PDM1-001, was a multi-center, randomized, placebo-controlled, double-blind, 3-arm parallel group study among approximately 42 healthy, premenopausal women with symptomatic primary dysmenorrhea. This study was designed to assess the systemic (plasma) and local mucosal (vaginal fluid) diclofenac PK and safety after a single dose and during three daily doses of vaginally administered DARE-PDM1, given in two different strengths (1% or 3% diclofenac in 2.5 mL of hydrogel) versus placebo (vaginal hydrogel, no active ingredient). The study also assessed, as an exploratory endpoint, the preliminary dysmenorrhea treatment efficacy of DARE-PDM1, when dosed in three daily doses at the onset of dysmenorrhea symptoms, compared to a no-treatment, baseline, control cycle. The study observation period encompassed approximately three menstrual cycles. The plasma PK results are forthcoming.
“We are encouraged by these data which indicate that our candidate, DARE-PDM1, was well-tolerated and safe for premenopausal women in both treatment groups,” said Dr. Annie Thurman, Medical Director of Daré Bioscience. “The most common interventions for primary dysmenorrhea include oral NSAIDs and hormonal contraceptives, which often can produce undesirable side effects such as an increased risk of gastrointestinal adverse events, including nausea, vomiting, bloating, or ulcerations. These topline phase 1 data indicate that by leveraging a vaginal route of administration, we can provide a more convenient and accessible treatment option for women that addresses the pain-related symptoms of the condition while minimizing side effects commonly seen with the use of oral medications.”
“DARE-PDM1 utilizes a well-known and well-characterized active pharmaceutical ingredient for primary dysmenorrhea delivered by our novel hydrogel technology, which is designed to keep the product from leaking out of the vagina and may increase the vaginal residence time,” said David Friend, chief scientific officer for Daré Bioscience. “The PK findings support that the product is retained in the vagina for a prolonged period, which we believe will contribute to the efficacy of the treatment.”
DARE-PDM1 phase 1 topline results indicate that the study treatment was well-tolerated, and treatment emergent adverse events profiles were comparable between the DARE-PDM1 treatment groups and the placebo group. All adverse events were mild or moderate; most adverse events (85%) were mild. There were no early discontinuations due to an adverse event, and no serious adverse events were reported.
The vaginal fluid PK results exhibited dose proportionality for the 1% and 3% diclofenac strengths of the DARE-PDM1 study treatment. Additionally, the vaginal fluid PK results demonstrated that the product was retained in the vaginal canal through 24 hours, which is similar to the vaginal retention demonstrated in the PK study of Daré’s FDA-approved vaginal gel product, which uses the same proprietary hydrogel technology.
The exploratory endpoint that evaluated the efficacy of DARE-PDM1 versus placebo in reducing dysmenorrhea-associated pain showed a promising signal, with a statistically significant decrease in pelvic/vaginal and lower back pain scores in the 1% diclofenac DARE-PDM1 treatment group compared to the placebo group, as well as a decrease in pain scores in the 3% diclofenac DARE-PDM1 treatment group. Additionally, while most participants used at least one non-pharmacologic pain relief method (e.g., heating pad) for dysmenorrhea-associated pain during the no-treatment, baseline, control cycle, the proportion of participants who used at least one non-pharmacologic pain relief method for dysmenorrhea-associated pain decreased significantly in the DARE-PDM1 treatment groups during the dosing period, but not in the placebo group. There was no difference in the exploratory assessment of frequency of use of rescue medications in the treatment phase between the three groups.
Primary dysmenorrhea is defined as painful menstruation in women with normal pelvic anatomy, typically described as cramping pain in the lower abdomen before or during the menstrual period. Recent market research suggests that the global market for dysmenorrhea treatment was estimated to be valued at USD$13 billion in 2022 and that the size of this market is expected to increase to USD $28.5 billion by 2029. Oral NSAIDs, such as oral diclofenac products, are often recommended for temporary relief from the painful symptoms of primary dysmenorrhea. Because there are currently no FDA-approved vaginal diclofenac treatment options for primary dysmenorrhea, DARE-PDM1 has the potential to be a first-in-category product, delivering diclofenac in a convenient vaginal format that may extend the duration of pain relief and reduce the risks associated with the oral delivery of NSAIDs.