Australian antiviral drug development company Island Pharmaceuticals has completed subject dosing for the phase 2b therapeutic arm of its phase 2a/b PROTECT clinical trial of ISLA-101 for dengue fever treatment. The company successfully administered ISLA-101 to all 10 subjects in the phase 2b cohort on schedule with no delays, marking a significant milestone in the development of a potential dengue treatment.
Trial Design and Progression
The phase 2 PROTECT study is divided into two distinct cohorts: a phase 2a prophylactic (preventative) arm and a phase 2b therapeutic (treatment) arm. The phase 2b arm is specifically designed to assess whether ISLA-101 can reduce virus levels and symptoms in subjects already infected with the dengue challenge virus, which is an attenuated or weakened strain of dengue.
Subject enrollment for the phase 2b arm began in January 2025 following a positive assessment by Island's Safety Review Committee (SRC) on data from the phase 2a cohort. The SRC's review determined that key benchmarks for safety and anti-dengue activity had been met, providing a strong platform to proceed to phase 2b trials for the therapeutic application of the treatment.
Safety Review and Regulatory Approval
The SRC's recommendations were submitted to the US Food and Drug Administration (FDA) for the recommended 30-day review period prior to the start of the phase 2b cohort. The committee's review of phase 2a data confirmed that ISLA-101 was safe and exhibited antiviral activity, enabling progression to the therapeutic testing phase.
Between the two studies, Island aims to understand if ISLA-101 can be an effective prophylactic and/or therapeutic against a dengue infection. The primary endpoint of the phase 2b trial is viremia reduction - measuring the virus load in the bloodstream of subjects. Other endpoints include confirming the safety of ISLA-101 and achieving a reduction in symptoms associated with dengue infection.
Clinical Significance and Market Opportunity
Dengue fever is the most prevalent mosquito-borne viral disease, and according to the World Health Organization, its incidence has grown dramatically around the world in recent decades, with no specific treatment currently available. This represents a significant unmet medical need in global healthcare.
Island executive chairman Phil Lynch emphasized the scale of the opportunity, stating: "The most recent 2a clinical results show the potential for a preventative approach to dengue management that could aid millions of travellers who visit exposed countries, with malaria treatment a useful analogue to quantify this opportunity."
Timeline and Expected Results
High-level results from the phase 2b studies are anticipated in the next six to eight weeks. Island's managing director and CEO Dr David Foster noted that high-level results from the phase 2b study are expected around April 2025, with full results from the unblinded data of both the phase 2a and phase 2b cohorts expected in Q4 FY25.
Dr Foster described the completion of enrollment as "a significant advancement in our clinical trial and towards better understanding the potential of ISLA-101 as a treatment for dengue fever." He added that the company looks forward to "further positive results from the 2b trial, and thereafter the opportunity to progress ISLA-101 as a potential therapeutic treatment also, for what remains a significant unmet consumer healthcare need."
