Hormonal health
FDA approves application for investigational hormone-free contraceptive
Ovaprene could become the first FDA-approved monthly, self-administered, hormone-free contraceptive product
The Food & Drug Administration has approved an Investigational Device Exemption (IDE) application to allow the US company Daré to conduct an efficacy study of its hormone-free contraceptive.
Daré Bioscience, a clinical-stage biopharmaceutical company aiming to advance innovative products for women’s health, has designed Ovaprene to prevent pregnancy by releasing a locally acting, non-hormonal agent which impedes sperm motility, and physically blocking sperm from entering the cervical canal with a knitted polymer barrier.
The IDE approval reflects that the FDA determined the company provided sufficient data to support the initiation and conduct of the study.
The IDE submission included the results of the postcoital test (PCT) clinical study of Ovaprene, in which Ovaprene prevented all sperm from entering the cervical canal across all women and all cycles evaluated. PCT clinical trials have been used as a surrogate marker for contraceptive effectiveness.
“We are driven to bring forward innovative options that support women’s health and wellness, and we are motivated to accelerate the development and introduction of differentiated product candidates, like Ovaprene, which is both hormone-free and designed to be conveniently kept in place vaginally continuously over the weeks between menstruation,” said Sabrina Martucci Johnson, president & CEO of Daré Bioscience.
“When it comes to contraception, many of the top-selling brands in the category are delivering both convenience and efficacy, suggesting that women and healthcare providers have a preference for contraceptive methods that are effective, that don’t need to be administered every day, and that don’t require action at the time of intercourse.”
In order for the planned study to serve as the primary clinical support for a future marketing approval or clearance, the FDA provided additional study design considerations with the IDE approval letter.
“The FDA communication confirms our alignment on a number of key aspects of the clinical study, including the adequacy of a 12-month (13 menstrual cycles) duration,” explained Johnson.
“The additional study design considerations provided by the FDA are considered by the administration to be recommendations that do not need to be addressed in order for us to initiate and conduct this study. However, implementing the guidance that we received will further position this pivotal study to collect safety and effectiveness data that will support the submission of a Premarket Approval (PMA) application.
“We look forward to working with our collaborators at the NIH and at Bayer to review and implement the recommendations and we are targeting mid-year 2023 study recruitment initiation.”
The single arm, non-comparative, pivotal Phase 3 contraceptive study of Ovaprene will evaluate its effectiveness as a contraceptive device along with its safety and usability. If successful, Daré expects the pivotal study to support marketing approvals of Ovaprene in the US and other countries.
In January 2020, Daré and Bayer announced an exclusive licensing agreement for US commercial rights to Ovaprene. Under the agreement, Daré received an upfront payment and access to Bayer’s extensive clinical and market capabilities while retaining control over Ovaprene’s development and regulatory approval process.
Bayer received the right to obtain exclusive rights to commercialise the product in the US following completion of the clinical trial being undertaken by Daré.
If Ovaprene is approved by the FDA, it could be the first monthly non-hormonal contraceptive product for women and a first-in-category option for women seeking a hormone-free, self-administered and monthly birth control method.
Insight
Topical HRT protects bone density in women with period loss – study
Transdermal HRT best protects bone density in women with functional hypothalamic amenorrhoea, a condition that stops periods, a review of trials has found.
The meta-analysis pooled randomised clinical trials involving 692 participants and found transdermal hormone replacement therapy and teriparatide increased bone mineral density by between 2 and 13 per cent.
Functional hypothalamic amenorrhoea can follow anorexia or intense exercise. Bone mineral density measures bone strength and the amount of mineral in bone.
Around half of women with the condition have low bone mineral density, compared with about 1 per cent of healthy women, and their fracture risk is up to seven times higher.
The research was conducted by scientists at Imperial College London and Imperial College Healthcare NHS Trust.
Professor Alexander Comninos, senior author of the study and consultant endocrinologist at the trust, said: “Bone density is lost very rapidly in FHA and so addressing bone health early is very important to reduce the lifelong risk of fractures.
“Our study provides much needed comparisons of all the available treatments from all available studies.
“Clearly the best treatment is to restore normal menstrual cycles and therefore oestrogen levels through various psychological, nutritional or exercise interventions – but that is not always possible.
“The foundation for bone health is good calcium and vitamin D intake (through diet and/or supplements) but we have additional treatments that are more effective.”
When FHA is diagnosed, clinicians first try to restore periods through lifestyle measures, including psychological and dietary support, but these can fail. Guidelines then recommend giving oestrogen, though the best form was unclear.
The team reviewed all prior randomised trials comparing therapies, including oral and transdermal oestrogen, and also assessed teriparatide, a prescription bone-building drug used for severe osteoporosis.
They found no significant benefit for oral contraceptive pills or oral hormone therapy.
A recent UK audit reported that about a quarter of women with anorexia-related FHA are prescribed the oral contraceptive pill for bone loss; the study suggests using transdermal therapy instead.
Comninos said: “Our goal is simple: to help women receive the right treatment sooner and to protect their bone health in the long-term.
“We hope this study provides clinicians with better evidence to choose transdermal oestrogen when prescribing oestrogen and so inform future practice guidelines.
“Right now, millions of women with FHA may not be receiving the best treatments for their bone health.”
Entrepreneur
US startup builds wearable hormone tracker
Wellness
IBSA UK launches non-hormonal injectable for menopause symptoms
IBSA UK has introduced Hyaluxelle, a non-hormonal menopause treatment for vulvo-vaginal atrophy, easing vaginal dryness and pain during intercourse.
Hyaluxelle is given as deep intradermal injections to the vulvar vestibule, the area at the vaginal opening, in two sessions one month apart, followed by clinical reassessment.
IBSA UK is the UK subsidiary of Swiss pharmaceutical company IBSA.
Vulvo-vaginal atrophy is a key feature of genitourinary syndrome of menopause, a long-term condition caused by low oestrogen that affects genital, urinary and sexual health.
At least half of post-menopausal women are affected, yet many do not seek help, often assuming symptoms are part of ageing.
The condition stems from thinning and drying of vaginal and vulval tissues linked to low oestrogen, leading to symptoms such as dryness, discomfort, altered pH and pain during intercourse.
Hyaluxelle combines high and low molecular weight hyaluronic acid, a moisture-retaining substance found naturally in the body.
The company says this creates a lower-viscosity injection at what it describes as the highest concentration available in the UK, supporting tissue hydration, firmness and elasticity.
The formulation is said to rehydrate the vulvar vestibule and create conditions for restoring tissue structure through collagen and elastin production.
Clinical studies indicate Hyaluxelle improves several vulvo-vaginal symptoms, including reductions in discomfort and pain during intercourse.
Studies also report gains in sexual function domains and a positive trend in some aspects of health-related quality of life.
Histological analyses suggest increased epithelial thickness, enhanced tissue regeneration and reduced inflammatory infiltration after the procedure. In studies, the treatment was well tolerated with no reported major complications.
Joanna, a 59-year-old woman living with severe symptoms, described the personal impact of delayed diagnosis.
She said: “I lived for years with pain, UTIs, cystitis and a loss of sensation, but every visit to my GP, even a female GP, was treated as a bladder issue.
“Nobody suggested it might be linked to the menopause or joined the dots, and none of the treatments I was given helped. Without the right information or support, I became desperate for answers.
“The symptoms affected everything, what I wore, how I exercised, how I slept, but the hardest part was the impact on intimacy with my husband.
“I withdrew from our relationship because I was scared sex would hurt, and the loss of closeness was devastating, and I no longer felt like myself.
“Women deserve clear explanations and real options when their symptoms are not getting better.”
IBSA says Hyaluxelle offers clinicians an option for women whose symptoms persist despite first-line therapies, or for those who cannot receive or choose not to receive hormonal treatments.
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