DARE-HPV

Our Pipeline:

Potential first-in-category non-surgical treatment for HPV-related cervical disease*

About HPV-Related Diseases

Human papillomavirus (HPV) is the most common sexually transmitted infection in the United States. There are 51 different types of HPV that can affect the genitals^1,2, with the potential to cause health problems including genital warts and cervical, anal, vulvar, penile, and oropharyngeal cancers. Essentially all cervical cancers worldwide are caused by infection with one of 14 carcinogenic, or “high-risk” HPV types (hrHPV)^1,3,4. While HPV vaccination continues to be a key tool, HPV treatments will also continue to be a key pillar in cervical cancer prevention due to suboptimal vaccine uptake⁵ and because the vaccine doesn’t cover all strains of hrHPV⁶.

While some HPV infections are transient, persistent hrHPV infection can progress to cervical cancer through a series of lesions (abnormal cell growth on the cervix) called cervical intraepithelial neoplasia (CIN). Today, for women with persistent HPV infection or early-stage cervical lesions (low-grade squamous intraepithelial lesion (LSIL) or CIN 1), there is no standard-of-care medical treatment; management is a “watchful waiting” approach that recommends repeat HPV testing every 12 months⁷. For those who progress to late-stage cervical lesions (high-grade squamous intraepithelial lesion (HSIL) and CIN 2/3), the most common treatment is a surgery called a loop electrosurgical excision procedure or LEEP. This procedure uses a small wire loop that is attached to an electrical current which is used to cut away the layer of abnormal cells⁸. While the most common complication with LEEP is heavy bleeding, it is also associated with an increased risk of preterm birth and sexual dysfunction and is therefore not recommended for patients with fertility concerns^8,9.

In the U.S. about 10% of women with HPV infection on their cervix will develop long-lasting HPV infections, of which approximately 14,000 will be newly diagnosed with cervical cancer this year, and more than 4,000 will die from the disease in 2024^10,11,12. Additionally, each year in the U.S., an estimated 100,000 people are treated for cervical precancer³, of which approximately 74% are between the ages of 18–39 years¹³, during prime childbearing and childrearing years.

Our Investigational Candidate, DARE-HPV

DARE-HPV is an investigational, proprietary fixed-dose formulation of lopinavir and ritonavir in a soft gel vaginal insert with the potential to be a first-in-category treatment for HPV-related cervical diseases. Lopinavir prevents cleavage of key viral polyproteins resulting in the formation of immature non-infectious viral particles and is one of the active ingredients in the HIV treatment, Kaletra® (lopinavir and ritonavir) tablet for oral use and oral solution¹⁴. Ritonavir boosts the activity of lopinavir^15,16. Ritonavir is also one of the active ingredients in the COVID-19 treatment, Paxlovid™ (nirmatrelvir tablets; ritonavir tablets), co-packaged for oral use¹⁷. In a pilot study of vaginally-administered lopinavir and ritonavir in 23 women in Kenya with late-stage cervical lesions, approximately 78% of the women demonstrated no dysplasia or a reduction to low-grade lesions after 12 weeks of treatment, and HPV was no longer detected in approximately 52% of the women.

There currently are no FDA-approved, non-surgical pharmaceutical interventions to treat CIN 2+ and no FDA-approved treatments for HPV infection. DARE-HPV has the potential to be the first pharmaceutical intervention for the treatment of CIN and other HPV-related cervical pathologies. Daré is currently conducting key IND-enabling activities to support moving forward into a Phase 2 clinical study.

*This page includes forward-looking statements subject to qualifications described in the Terms of Service, including Section 13.4, Forward-Looking Statements; Disclaimer

DARE-HPV Footnotes:

Schmitt M, Depuydt C, Benoy I, Bogers J, Antoine J, Arbyn M, Pawlita M, VALGENT Study Group. Prevalence and viral load of 51 genital human papillomavirus types and three subtypes. Int J Cancer. 2013 May 15;132(10):2395–2403. PMID: 23034864
Bernard HU, Burk RD, Chen Z, van Doorslaer K, zur Hausen H, de Villiers EM. Classification of papillomaviruses (PVs) based on 189 PV types and proposal of taxonomic amendments. Virology. 2010 May 25;401(1):70–79. PMCID: PMC3400342
Perkins RB, Wentzensen N, Guido RS, Schiffman M. Cervical Cancer Screening: A Review. JAMA. 2023 Aug 8;330(6):547–558. PMID: 37552298
Ramakrishnan S, Partricia S, Mathan G. Overview of high-risk HPV’s 16 and 18 infected cervical cancer: pathogenesis to prevention. Biomed Pharmacother. 2015 Mar;70:103–110. PMID: 25776487
S. Department of Health and Human Services. Increase the proportion of adolescents who get recommended doses of the HPV vaccine – IID‑08. https://health.gov/healthypeople/objectives-and-data/browse-objectives/vaccination/increase-proportion-adolescents-who-get-recommended-doses-hpv-vaccine-iid-08 Accessed 2024 October 7.
National Cancer Institute at the National Institutes of Health. HPV and Cancer. Updated: October 18, 2023. https://www.cancer.gov/about-cancer/causes-prevention/risk/infectious-agents/hpv-and-cancer#hpv-vaccine-preventing-hpv-infection.
Perkins RB, Guido RS, Castle PE, Chelmow D, Einstein MH, Garcia F, Huh WK, Kim JJ, Moscicki AB, Nayar R, Saraiya M, Sawaya GF, Wentzensen N, Schiffman M; 2019 ASCCP Risk-Based Management Consensus Guidelines Committee. 2019 ASCCP Risk-Based Management Consensus Guidelines for Abnormal Cervical Cancer Screening Tests and Cancer Precursors. J Low Genit Tract Dis. 2020 Apr;24(2):102-131. doi: 10.1097/LGT.0000000000000525. Erratum in: J Low Genit Tract Dis. 2020 Oct;24(4):427. doi: 10.1097/LGT.0000000000000563. PMID: 32243307; PMCID: PMC7147428.
National Cancer Institute at the National Institutes of Health. HPV and Pap Test Results: Next Steps after an Abnormal Cervical Cancer Screening Test. Updated: 2024 June 6. https://www.cancer.gov/types/cervical/screening/abnormal-hpv-pap-test-results#_35.
Litman, E, Cigna, S. Female Sexual Dysfunction in Women After Treatment of Cervical Dysplasia. Sex Med Rev 2022;10:360–366. https://doi.org/10.1016/j.sxmr.2022.02.003.
S. Centers for Disease Control and Prevention. Basic Information about HPV and Cancer. [Internet]. https://www.cdc.gov/cancer/hpv/basic-information.html. Accessed 2024 Oct 10.
American Cancer Society. Key Statistics for Cervical Cancer [Internet]. Available at: https://www.cancer.org/cancer/types/cervical-cancer/about/key-statistics.html. Accessed 2024 Sept 16.
S. Centers for Disease Control and Prevention. Cervical Cancer Statistics. [Internet]. Available at: https://www.cdc.gov/cervical-cancer/statistics/index.html. Accessed 2024 Sept 16.
McClung NM, Gargano JW, Park IU, Whitney E, Abdullah N, Ehlers S, Bennett NM, Scahill M, Niccolai LM, Brackney M, Griffin MR, Pemmaraju M, Querec TD, Cleveland AA, Unger ER, Markowitz LE, HPV-IMPACT Working Group, HPV-IMPACT Working Group, Blankenship S, Allen S, Meek J, Higgins K, Hadler J, Sosa L, Saadeh K, Fink D, Silverberg M, Powell ME, Allain SQ, Felsen C, Bogart R, Feiler MO, Dahl RM. Estimated Number of Cases of High-Grade Cervical Lesions Diagnosed Among Women — United States, 2008 and 2016. MMWR Morb Mortal Wkly Rep. 2019 Apr 19;68(15):337–343.
KALETRA Prescribing Information. Revised: 10/2020. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/021251s059,021906s054lbl.pdf.
DrugBank Online. Ritonavir. https://go.drugbank.com/drugs/DB00503. Accessed 2024 Sept 16.
Talha B, Dhamoon AS. Ritonavir. [Updated 2023 Aug 8]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK544312/.
PAXLOVID Prescribing Information. Revised: 9/2024. https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/217188s006lbl.pdf