^{Menopause and osteoporosis pipeline; Source: IQVIA Pipeline Link, July 2023; IQVIA EMEA Thought Leadership analysis}

Menopause innovation: nonhormonal treatments for vasomotor symptoms

To assess pharmaceutical industry activity addressing the burden of disease for women’s reproductive health, we investigated the pipelines for menopause and osteoporosis.

A particular focus of these efforts has been vasomotor symptoms (VMS)  (hot flashes and night sweats; which affect approximately 70% of women during the menopause, with symptoms lasting an average of 7 years^6,7. After a decade with no new non-hormonal products being approved for menopausal VMS, this area has recently seen some much-needed innovation, with the FDA’s approval of Astellas’s Veozah earlier this year. This first-in-class neurokinin 3 receptor (NK3R) antagonist will provide an alternative to HRT for women with a history of breast cancer or blood clots, and those who prefer non-hormonal treatment. Bayer has another NKR antagonist in phase 3 trials, following its 2020 acquisition of KaNDy Therapeutics. Other innovative approaches in phase 2 trials include Daré Bioscience’s intravaginal ring that delivers estradiol and progesterone over 28 days, eliminating the need for a daily intervention like most HRT, and Vistagen’s rapid-onset nasal spray to treat VMS and migraines.

Osteoporosis: a common, under-treated, cause of death and disability in postmenopausal women

Osteoporosis is a significant cause of death and disability worldwide, particularly in postmenopausal women. It is estimated that 200 million women have osteoporosis, including 10% of women over the age of 60 and 20% of those over 70⁸. Fractures due to osteoporosis rarely result in death directly, but they often cause a downwards spiral in health and independence, with life changing consequences for elderly women and wider impacts for healthcare systems. Approximately 20% of hip fracture patients die within a year, with 40% of survivors unable to walk independently one year later⁹. In US women aged 55 and older, osteoporotic fractures have a higher hospitalisation burden and associated cost than myocardial infarction, stroke or breast cancer¹⁰.

HRT has been approved for the prevention of postmenopausal osteoporosis since 1988 and is still recommended as a first-line therapy to prevent osteoporosis-related fractures for women under 60 or within 10 years after menopause¹¹. However, as described above, HRT use has declined since the WHI. The most common treatment is bisphosphonates, more modern, once weekly, versions of which have been used since 1995. However, they can cause oesophageal ulceration so patients must remain upright for 30-60 minutes after taking them, with once weekly versions partially addressing this issue by reducing the time often frail patients must do this for. Two first-in-class injectable biologics, Prolia (denosumab), a RANKL inhibitor which blocks bone breakdown, and Evenity (romosozumab), a sclerostin inhibitor which enhances bone formation, were the highest-selling osteoporosis products in 2022, approved in 2010 and 2019 respectively. Following these, there is a lack of innovative products in development: while there are osteoporosis products in pipelines, of those for which this information is available, none have new molecular targets.

Even with current prevention and treatment options, osteoporosis is under-diagnosed and under- treated¹². only 27% of women eligible for osteoporosis medication are being treated¹³. Screening, particularly in women aged 50-60, should therefore be a priority. A 2020 meta-analysis found that population screening using bone densitometry and fracture risk assessment, followed by targeted treatment, significantly reduces osteoporotic fractures¹⁴.

Can female health technology improve menopause care?

Over the last few years, there has been a rise in mobile applications and devices aimed at improving women’s health. The global female health technology (or ‘FemTech’) market was valued at $19 billion in 2019 and is forecast to be worth $60 billion in 2027¹⁵. From January to August 2021, digital health start-ups aimed at women raised $1.3bn across 26 deals, with 31% of these being Series C or above. This is twice as much as was raised in the same period in 2020, and accounts for 7% of overall digital health funding¹⁶. The telehealth platform Maven Clinic became the first women-focused digital health start-up to achieve ‘unicorn’ status with a $1bn valuation in 2021¹⁷. Marketed primarily towards employers, it connects women with healthcare specialists across fertility, maternity and parenting, and began offering menopause care services last year.

Menopause care lags behind other sectors in terms of digital health funding, with $79m raised relative to $316m and $330m for companies targeting pregnancy, postpartum and parenthood, and fertility, respectively, in 2021¹⁸. However, with telemedicine uptake continuing to increase, particularly among women and those aged over 55, healthcare technology has a role to play in addressing unmet needs in this area¹⁹.

Conclusion

The menopause is a significant health event in the lives of billions of the world’s population. The way in which menopause affects women can be highly variable, but for some women serious health issues such as cardiovascular diseases, osteoporosis, and cancers can manifest around or following the menopause, and immediate menopausal symptoms such as hot flashes have significant quality of life impact on many more women. With rising life expectancies, women expect to be able to enter their menopausal and post-menopausal years with decades of good quality, healthy life ahead of them. Many existing pharmacotherapeutics are valuable resources but overall, too much of what is available is old, comes with significant caveats, and does not reflect the needs of the new generations of women now entering the menopause. The renaissance in valuable innovation in other high prevalence, chronic and often age-related conditions, notably cardiometabolism and CNS areas, as detailed in IQVIA’s white papers A renaissance for Cardiometabolic innovation²⁰ and Two steps forward, one step back: the long road to success in CNS²¹ outline the potential that these areas have when the right innovation is developed to address long standing unmet needs. The coming years may well see a change for the change in terms of healthcare provision.

References

¹Menon U, Burnell M, Sharma A, et al. Decline in use of hormone therapy among postmenopausal women in the United Kingdom. Menopause. 2007;14(3):462-467

²Lobo RA. Hormone-replacement therapy: current thinking. Nat Rev Endocrinol. 2017;13(4):220-231. doi:10.1038/nrendo.2016.164

³https://www.gov.uk/government/news/hundreds-of-thousands-of-women-experiencing-menopause-symptoms-to-get-cheaper-hormone-replacement-therapy

⁴Alsugeir, D., Wei, L., Adesuyan, M., Cook, S., Panay, N., & Brauer, R. (2022). Hormone replacement therapy prescribing in menopausal women in the UK: a descriptive study. BJGP open, 6(4), BJGPO.2022.0126. https://doi.org/10.3399/BJGPO.2022.0126

⁵Faubion SS, Enders F, Hedges MS, et al. Impact of Menopause Symptoms on Women in the Workplace. Mayo Clin Proc. 2023;98(6):833-845. doi:10.1016/j.mayocp.2023.02.025

⁶Thurston, R. C., Sutton-Tyrrell, K., Everson-Rose, S. A., Hess, R., & Matthews, K. A. (2008). Hot flashes and subclinical cardiovascular disease: Findings from the Study of Women’s Health Across the Nation Heart Study. Circulation, 118, 1234–1240.

⁷Avis NE, Crawford SL, Greendale G, et al. Duration of Menopausal Vasomotor Symptoms Over the Menopause Transition. JAMA Intern Med. 2015;175(4):531–539. doi:10.1001/jamainternmed.2014.8063

⁸Lorentzon M, Johansson H, Harvey NC, et al. Osteoporosis and fractures in women: the burden of disease. Climacteric. 2022;25(1):4-10. doi:10.1080/13697137.2021.1951206

⁹Leibson CL, Tosteson AN, Gabriel SE, Ransom JE, Melton LJ. Mortality, disability, and nursing home use for persons with and without hip fracture: a population-based study. J Am Geriatr Soc. 2002;50(10):1644-1650. doi:10.1046/j.1532-5415.2002.50455.x

¹⁰http://www.bonehealthandosteoporosis.org/wp-content/uploads/2016/01/1047.pdf

¹¹de Villiers TJ, Gass ML, Haines CJ, et al. Global consensus statement on menopausal hormone therapy. Climacteric. 2013;16(2):203-204. doi:10.3109/13697137.2013.771520

¹²https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4520366/

¹³https://doi.org/10.1080/13697137.2021.1951206

¹⁴https://pubmed.ncbi.nlm.nih.gov/31838551/

¹⁵https://www.emergenresearch.com/industry-report/femtech-market

¹⁶https://rockhealth.com/rock-weekly/the-new-billion-dollar-wave-in-women-digital-health/

¹⁷https://fortune.com/2021/08/17/maven-clinic-fundraise-series-d-unicorn-women-family-health/

¹⁸https://rockhealth.com/insights/building-comprehensive-women-digital-health-eight-sectors-serving-women-needs/

¹⁹https://rockhealth.com/insights/consumer-adoption-of-digital-health-in-2022-moving-at-the-speed-of-trust/

²⁰https://www.iqvia.com/library/white-papers/a-renaissance-for-cardiometabolic-innovation

²¹https://www.iqvia.com/library/white-papers/two-steps-forward-one-step-back-the-long-road-to-success-in-cns