Breakthrough in Treatment of Cervical High-Grade Squamous Intraepithelial Lesion: Release of Positive Results from Multicenter Phase III Global Clinical Study
This study is a prospective, randomized, double-blinded, placebo-controlled multicenter Phase III global clinical study designed to evaluate the efficacy and safety of APL-1702 for the treatment of cervical HSIL.
- The world's first non-surgical cervical HSIL treatment validated by an international Phase III clinical study with proven efficacy;
- The response rate increased by 89.4% compared to the placebo control group, with a low incidence of adverse events;
- The China new drug application submission is expected in Q2 2024, while ex-China product development is in active progress.
SHANGHAI, March 18, 2024 /PRNewswire/ -- Asieris Pharmaceuticals (Stock Code: 688176.SH), a global biopharmaceutical leader in the discovery, development, and commercialization of innovative drugs for genitourinary tumors and related diseases announced that the multicenter Phase III global clinical study data of its non-surgical treatment for cervical HSIL product APL-1702 demonstrated significant efficacy and good safety profile, with new advancements in clearance rate of high-risk HPV16 and/or HPV18. Key data from the study were presented in oral presentations at the 2024 European Research Organization on Genital Infection and Neoplasia (EUROGIN) Congress and the 2024 Society of Gynecologic Oncology (SGO) Annual Meeting.
APL-1702 is a pioneering cold light photodynamic drug-device combination product, used as a non-surgical therapy for treating cervical HSIL. This study is a prospective, randomized, double-blinded, placebo-controlled multicenter Phase III global clinical study designed to evaluate the efficacy and safety of APL-1702 for the treatment of cervical HSIL. Primary endpoint of the study is the proportion of responders at 6 months after the initial treatment. The study is led by Dr. Jinghe Lang, an academician at Peking Union Medical College Hospital, Chinese Academy of Medical Sciences. Response is defined as the conversion of cervical epithelial tissue pathology to normal or the conversion to low-grade squamous intraepithelial lesion (LSIL) while achieving baseline HPV clearance.
According to the study results, between November 2020 and July 2022, a total of 402 eligible patients from various countries including China, Germany, the Netherlands et al. were randomized and enrolled in this study. The response rate in the APL-1702 treatment group showed a statistically significant improvement of 89.4% (41.1% vs. 21.7%, p = 0.0001) compared to that in the placebo control group, indicating a remarkable therapeutic effect. Additionally, APL-1702 showed an improved clearance rate of high-risk HPV16 and/or HPV18, with a 103.9% increase in the APL-1702 treatment group compared to the control group (31.4% vs. 15.4%)[1]. The incidence of treatment-emergent adverse events (TEAEs) was comparable between the treatment group and the control group, with the majority being mild and self-healing without requiring intervention. The occurrence rates of treatment-related adverse events (TRAEs) and serious adverse events (SAEs) were both low in both groups[2].
According to the "Global Cancer Statistics 2020" report, there were 604,127 new cases of cervical cancer in women worldwide in 2020, with 341,831 deaths, ranking it as the fourth most common cancer among women. Cervical cancer incidence ranks second among malignant tumors in Chinese women. According to the "National Cancer Report 2024" released by the National Cancer Center, there were 150,700 new cases of cervical cancer in China in 2022, with 55,700 deaths from cervical cancer.
The main cause of cervical cancer is persistent infection with human papillomavirus (HPV), which leads to precancerous lesions of the cervix. Approximately 25% of individuals with HSIL may progress to invasive cervical cancer within 10 years[3]. According to Frost Sullivan analysis, it is projected that by 2030, the number of HSIL patients worldwide and in China will reach 16.6 million and 2.2 million, respectively. With the increasing popularity of dual-cancer screening and cervical cytology tests, more and more patients with cervical precancerous lesions are being detected at early stages before cancer develops, and it is expected that the number of patients will continue to increase.
Women with cervical precancerous lesions have unmet clinical needs for non-surgical therapies. Currently, invasive procedures such as loop electrosurgical excision procedure (LEEP) and cold knife conization remain the primary treatment options for high-grade cervical lesions. However, these surgical treatments are associated with adverse reactions including bleeding, infection, and cervical structural damage, which may lead to complications such as preterm birth and miscarriage. Furthermore, cervical precancerous lesions require long-term monitoring and management because even after surgical treatment, there is a risk of persistent disease or recurrence, with a higher risk of developing cervical cancer compared to the general population (5 times higher risk of invasive cancer within 10 years). Therefore, post-operative follow-up for at least 25 years is necessary. Importantly, if cervical precancerous lesions recur, subsequent surgical interventions become more challenging and carry higher risks, potentially resulting in total hysterectomy. Thus, early surgical intervention increases the difficulty of long-term management. Non-surgical therapies that preserve the intact cervix and avoid or delay cervical trauma are of significant importance for the long-term management of patients with cervical precancerous lesions.
Professor Chen Fei, Chief Physician of the Department of Obstetrics and Gynecology at Peking Union Medical College Hospital, expressed her delight with the research findings, stating, "I am extremely pleased with the results of this study. Treating HSIL serves as the final barrier against cervical cancer. Previous international studies on HSIL have not been successful, but this study, utilizing a multicenter trial design and strict definition of efficacy endpoints, has achieved positive results, which is no easy feat. As a clinician, I have encountered many HSIL patients who desire to preserve their intact cervix while receiving treatment. The emergence of APL-1702 will fulfill the wishes of these patients, allowing them to avoid or delay cervical trauma to the maximum extent possible."
Professor Qiao Youlin, a member of the WHO Global Expert Group for Cervical Cancer Elimination and a professor at the School of Population Medicine and Public Health at the Chinese Academy of Medical Sciences/Peking Union Medical College, believes that in addition to vaccination and screening, treatment of cervical precancerous lesions is a crucial component of secondary prevention for cervical cancer. However, progress in the field of medication for cervical precancerous lesions has been relatively slow, with high barriers to overcome, and there are currently no approved treatment drugs worldwide. "It is gratifying to see the emergence of innovative products like APL-1702, which simultaneously possess clinical value in addressing the treatment gap, public health value in cervical cancer prevention and control, and social value in promoting fertility-friendly options. This breakthrough will safeguard women's health and make a positive contribution to the acceleration of the 2030 global and Chinese action plans for cervical cancer elimination".
Dr. Linda Wu, Chief Development Officer of Asieris Pharmaceuticals, said, "We are extremely proud of the results from the international multicenter Phase III clinical study of APL-1702. The study not only demonstrates remarkable efficacy but also exhibits a favorable safety profile, offering a new powerful artillery for the national cervical cancer prevention and control system. We express our gratitude to all the patients, physicians, and researchers who participated in this study, as their support and dedication have been invaluable. We are actively preparing the new drug application for APL-1702 and plan to submit it in the second quarter of this year. Additionally, we are making significant progress in product development overseas, aiming to bring this innovative treatment to more patients as soon as possible."
References：
- EUROGIN: Photodynamic therapy with APL-1702 for high-grade squamous intraepithelial lesions (HSIL): results from a randomized phase Ⅲ global study (YHGT-CEV-1/APRICITY)
- SGO: APL-1702 long-term efficacy and safety for cervical histologic high-grade squamous intraepithelial lesions (HSIL): results from a randomized phase Ⅲ global study
- Gao Shujun, Sui Long. Standardized management and follow-up of high-grade squamous intraepithelial lesions of the cervix[J]. Chinese Journal of Practical Gynecology and Obstetrics. 2020,36(07):604-608.
About APL-1702(Cevira®)
APL-1702(Cevira®) is a breakthrough photodynamic drug-device combination product that is being developed for non-surgical treatment of high-grade precancerous lesions of the cervix. Cevira® holds the potential to serve the high unmet medical need for non-invasive treatment options for patients with HSIL in an outpatient setting, especially for young women of reproductive age. Asieris Pharmaceuticals entered into a license agreement with Photocure ASA (Photocure, PHO: OSE) to obtain the worldwide development and commercialization of Cevira® in July 2019. Cevira® is a registered trademark of Photocure ASA, based in Oslo, Norway.
About Asieris
Asieris Pharmaceuticals(688176.SH), founded in March 2010, is a global biopharma company specializing in discovering, developing and commercializing innovative drugs for the treatment of genitourinary tumors and other related diseases. We strive to improve human health to preserve patient's dignity. We aim to become a global pharma leader that integrates R&D, manufacturing and commercialization in our areas of focus, as we provide best-in-class integrated diagnosis and treatment solutions for patients in China and worldwide.
The company has been developing its proprietary R&D platform and core technologies, exploring new mechanisms of action, and efficiently screening and evaluating drug candidates. With a well-established in-house R&D system and expertise in global drug development, Asieris is committed to launching first-in-class drugs and other innovative products to address huge unmet needs in its areas of focus.
Asieris is also enhancing its pipeline for genitourinary diseases via proprietary R&D and strategic partnerships, while closely following cutting-edge technologies and therapeutics. The company strives to discover and identify unmet clinical needs, and adopts a forward-looking approach in product planning and life-cycle management. We aim to establish an outstanding portfolio that covers diagnosis and treatment in a bid to benefit more patients in China and globally.
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