Antiva Biosciences Reports Positive Phase 1b/2 Results for ABI-2280 in High-Risk HPV Treatment
核心洞察
Antiva Biosciences (搜索)' ABI-2280 achieved its primary endpoint with 46% of patients in the 3mg cohort demonstrating hrHPV negativity at Week 12 compared to 16% for placebo (p=0.0077).
The topical treatment showed durable efficacy with 87% of Week 12 responders maintaining hrHPV negativity at Week 24 based on interim data.
ABI-2280 demonstrated favorable safety and tolerability with most adverse events categorized as mild or moderate and localized to the treatment area.
Antiva Biosciences (搜索) announced positive top-line results from its Phase 1b/2 clinical trial of ABI-2280, an investigational topical treatment for oncogenic cervical high-risk human papillomavirus (hrHPV) infection. The randomized, double-blind, placebo-controlled study achieved its primary endpoint, demonstrating statistically significant improvements in hrHPV negativity rates at Week 12 compared to placebo.
Primary Efficacy Results
The study's most promising results came from the 3mg cumulative dose cohort, where patients received 1mg doses three times over two weeks. In this group, 46% of patients achieved hrHPV negativity at Week 12 for all hrHPV genotypes present at baseline, compared to only 16% of placebo patients (p=0.0077). The 3mg cohort also achieved statistically significant improvements over placebo for both secondary endpoints of complete hrHPV negativity at Week 12 and two or more consecutive hrHPV negative tests by Week 12.
A second treatment regimen involving a 5mg cumulative dose (1mg dosed five times over six weeks) showed 32% of patients achieving hrHPV negativity at Week 12, though this result did not reach statistical significance compared to placebo.
Durability of Response
Interim Week 24 data demonstrated notable durability of therapeutic activity. Among all patients in the study who reached Week 24, 87% of those who were hrHPV negative at Week 12 following ABI-2280 treatment maintained hrHPV negativity at Week 24. Both ABI-2280 treatment cohorts showed clear separation from placebo in hrHPV negativity at every observed timepoint throughout the study (Weeks 2, 4, 8, and 12).
Safety Profile
ABI-2280 demonstrated favorable safety and tolerability across all dose levels and regimens. The most frequently reported adverse events were categorized as mild or moderate and were localized to the lower genitourinary tract, consistent with the site of topical administration.
Clinical Context and Unmet Need
The results address a significant unmet medical need in women's health. Each year in the United States, over six million women become newly infected with cervical hrHPV. Currently, no approved therapeutic options exist for treating hrHPV infections, leaving patients in a "wait and see" approach while monitoring for disease progression or clearance.
"Women with persistent high-risk HPV have an approximately one-in-five chance of their infection progressing to pre-cancer or worse over four-to-six years, yet they do not have any options to treat the infection in the hopes of halting disease progression before this occurs," said Margaret Stanley, OBE, FMedSci, Hon FRCOG, FFPH, Professor Emeritus, University of Cambridge. "This reality highlights the clinical importance of the data generated in this study of ABI-2280, which demonstrated a 30 percent improvement in hrHPV negativity as compared to placebo, combined with a favorable safety and tolerability profile."
Approximately 30% of women with hrHPV fail to clear the virus within 12 months, categorizing them as having persistent cervical hrHPV infections. These patients face an estimated 20% chance of progression to pre-cancer or cancer over the following four-to-six years.
Study Design and Patient Population
The Phase 1b/2 trial enrolled 139 female patients aged 25-55 years who had documented hrHPV infection for at least one year without evidence of precancerous lesions worse than low-grade cervical intraepithelial neoplasia (CIN1). The study was conducted in two parts: Part A evaluated multiple placebo-controlled sentinel cohorts to determine safety, tolerability, and preliminary efficacy of various dose levels in two-week and six-week dosing regimens. Part B expanded the top cumulative doses from each regimen for further efficacy evaluation.
Mechanism of Action and Development
ABI-2280 works by blocking HPV replication and inducing apoptosis in HPV-infected cells. The compound is expected to have potent activity across all genotypes of HPV worldwide. Antiva has formulated ABI-2280 as a vaginal insert that enables at-home self-administration at diagnosis.
Next Steps
"We are very pleased with the top-line data readout from this trial of ABI-2280 as we believe it provides strong support for moving into a Phase 2b trial in women with high-risk HPV infections," said Elaine Chien, MD, FACOG, chief medical officer of Antiva. "We are thrilled to achieve clinically meaningful and statistically significant hrHPV negativity with the most frequently administered dose which provides a roadmap for potentially achieving even greater efficacy with optimized dosing strategies in Phase 2b."
Disease Burden
The prevalence of cervical hrHPV infection is estimated at 20% among U.S. females of reproductive age, representing approximately 19 million women. Globally, cervical cancer ranks as the fourth most common cancer in women. According to the World Health Organization, an estimated 660,000 women were diagnosed with cervical cancer worldwide and approximately 350,000 women died from the disease in 2022.