Phase II Single Arm, Open Label Study of Artesunate for the Treatment of Human Papilloma Virus Positive High Grade Cervical Intraepithelial Neoplasia (CIN2/3)

Cervical cancer is the fourth most common form of cancer in women globally. It is a significant cause of morbidity and mortality, with over half a million new cases and over 300,000 deaths per year despite being preventable and curable if detected early and managed effectively. Low- and middle-income countries (LMICs) are disproportionately affected, with 80% of cases and 90% of cervical cancer-related deaths occurring in low-resource settings. There is an urgent need to develop affordable therapeutics to manage this global oncology burden. For many women, travel costs, time off work, and childcare responsibilities represent significant barriers to engaging with cervical cancer screening, treatment, and follow-up.

The World Health Organization (WHO) cervical cancer elimination strategy has set a target to eliminate cervical cancer as a public health problem (target incidence <4/100,000 population). To be on track to achieve this by the end of the century, draft targets include: 90% of girls vaccinated against HPV by the age of 15 years; 70% of all women aged 30 to 49 years receiving at least two high-precision screening tests 10 years apart; and 90% of screen-positive women, as well as 90% of women diagnosed with cervical cancer, receiving treatment by 2030. Countries are called to meet the 90-70-90 targets by 2030 in order to progress toward cervical cancer elimination. It is estimated that over 62 million deaths due to cervical cancer could be prevented in the next 100 years through implementation of this strategy alongside HPV vaccination.

While survival rates from colorectal, breast, prostate, cervical, and lung cancer are improving in high-income countries (HICs) due to a combination of early detection and more effective treatments, cancer death rates in LMICs are increasing. This is in part because many lifesaving cancer treatments remain unaffordable in LMICs, where cancer remains a neglected disease. Novel drug development takes an average of 10-15 years to go from bench to clinic at an average cost of USD 1 billion. Repurposing of established drugs for new indications can shorten this pathway substantially and reduce development costs.

In Malaysia, cervical cancer is the fourth leading cause of cancer-related morbidity and mortality among women, with an annual incidence of 1,700 cases reported in 2018. At present, only approximately 25% of women participate in regular cervical screening, and many patients present with advanced disease, with five-year overall survival around 52%. There is an urgent need for effective, safe, and affordable treatments to improve survival.

Artesunate belongs to the artemisinin family of sesquiterpene trioxane anti-malarial agents derived from Artemisia annua L. (Sweet wormwood), which has been used in traditional Chinese medicine for centuries to treat a variety of conditions including fever, inflammation, and haemorrhage. Artesunate is approved for the treatment of uncomplicated and multidrug-resistant malaria, is listed on the WHO Essential Medicines List, and is available at low cost (approximately USD 1 per daily dose).