Human Papilloma Virus (HPV) is so common that nearly all sexually active men and women get the virus at some point in their lives. While many of these are transient infections, the infections that persist are known to drive the formation of malignancies, including cervical, anal, vulvar, penile, and oropharyngeal cancers.
The advent of the prophylactic vaccine for HPV 16/18 in 2006 and a nine-valent vaccine in 2015 were major steps forward in the fight against HPV-associated cancers by preventing infection by certain high-risk HPV subtypes. However, due to limitations in HPV subtypes covered by the vaccine, low adoption rates in the US, EU, and Japan, and limited access to the vaccines in developing countries, HPV infections and the disease states driven by such infections remain a major unmet clinical need. In the US alone, it is estimated that more than 5 million women are diagnosed with high-risk HPV (a subtype that can lead to cancer) every year.
Currently, women with persistent HPV infection and early-stage cervical disease (LSIL or CIN 1) are monitored with frequent office visits but are not treated. Women with pre-cancerous lesions and sexually transmittable infections who are told to “watch and wait” often experience anxiety and frustration over the lack of treatment options and are at risk of transmitting HPV to their partners. A safe and effective topical therapy for HPV infection would enable transform cervical care worldwide by enabling earlier disease intervention and interrupting disease transmission.
Cervical Cancer and CIN
Globally, cervical cancer is the fourth most common cancer in women and as such represents a major public health problem. In 2020, an estimated 604,000 women were diagnosed with cervical cancer worldwide and approximately 342,000 women died from the disease1. The high burden of cervical cancer in low- and middle-income countries reflects the lack of resources available in these areas for screening and treatment.
Although the incidence of cervical cancer in developed countries is significantly lower than the global prevalence, statistics show that cervical cancer disproportionately affects all underserved populations. For example, in the US, Black women have the highest incidence and mortality, followed closely by Hispanic women2; LGBT populations may also be at an increased risk due to fear of discrimination or negative experiences with the healthcare system3. In addition, for all races, both cervical cancer incidence and poorer outcomes are higher in rural populations4. These statistics reflect the barriers to screening, diagnosis, and treatment for cervical precancer due to poor access to clinics and shortage of gynecologists. A topical drug for CIN 2,3 that could be prescribed by general practitioners and self-administered by patients would improve access to treatment in the US and abroad and decrease morbidity and mortality.
Eliminating the need for surgical treatment for HSIL would have the added benefit of reducing the incidence of subsequent adverse pregnancy outcomes; this is particularly important since women treated for HSIL are usually of reproductive age. Studies have shown that women having excisional removal of HSIL are 2 to 3 times more likely to have premature delivery than untreated women, with attendant lower birth weight, higher rates of NICU admission and perinatal mortality5. A successful topical treatment for cervical precancer should provide women a treatment option that does not compromise their reproductive health.
ABI-2280 for HPV infection and CIN 2,3
ABI-2280 is a prodrug of an acyclic nucleoside phosphonate with known potent antiviral activity but poor cellular permeability and use-limiting systemic toxicity. Antiva is overcoming the challenges of the parent compound by applying our expertise in antiviral pro-drug chemistry and topical formulations to create a drug product that can be administered topically and that is rapidly taken up into epithelial cells.
The lead indication for
The intended use of topical drugs that clear HPV can potentially be extended to other pre-cancers attributed to HPV, such as vulvar (VIN 2,3) and anal (AIN 2,3) intraepithelial neoplasias. VIN 2,3 is a disease rapidly increasing in incidence, the majority of which is caused by HPV. AIN 2,3 affects both women and men, particularly men having sex with men (MSM). Current treatment of both AIN and VIN is limited primarily to surgical techniques that can result in scarring with poor overall success rates, undesirable outcomes that underscore the unmet medical need for an effective topical treatment.
“Worldwide there are more than 500,000 new cases and 300,000 deaths attributed to cervical cancer each year. This is a staggering statistic and especially tragic as there is no question that cervical cancer is a preventable disease. With a coordinated global program of vaccination, screening and treatment, cervical cancer can and should be eliminated within a generation. As a clinician, I see each case of cervical cancer as a failure on the part of the healthcare system and look forward to a time when we can claim more successes.”
- Singh, D., et al., Global estimates of incidence and mortality of cervical cancer in 2020: a baseline analysis of the WHO Global Cervical Cancer Elimination Initiative. Lancet Glob Health, 2022. https://www.sciencedirect.com/science/article/pii/S2214109X22005010
- Kaiser Family Foundation, Cervical Cancer Incidence Rate per 100,000 Women by Race/Ethnicity. KFF/State Health Facts, 2018. https://www.kff.org/4d860fe/
- American Cancer Society, Cancer Facts for Lesbian and Bisexual Women. ACS/Cancer Facts: Prevention and Screening, 2021. https://www.cancer.org/healthy/cancer-facts/cancer-facts-for-lesbian-and-bisexual-women.html
- ACOG, Committee Opinion No. 586: Health disparities in rural women. Obstet Gynecol, 2014 (Reaffirmed 2019). 123(2 Pt 1): p. 384-388. https://www.acog.org/clinical/clinical-guidance/committee-opinion/articles/2014/02/health-disparities-in-rural-women
- Kyrgiou, M., et al., Obstetric outcomes after conservative treatment for cervical intraepithelial lesions and early invasive disease. Cochrane Database Syst Rev, 2017. 11(11): p. Cd012847. https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD012847/pdf/full