Unmet Need:Human immunodeficiency virus (HIV) infection and acquired immune deficiency syndrome (AIDS) are amongst the most serious and challenging health problems in the world. There are nearly 37 million people worldwide living with HIV/AIDS and approximately 1 million AIDS-related deaths have occurred in 2017 alone - about 5,000 new infections per day (WHO website).
Antiretroviral therapy (ART) has led to substantial improvements in the life expectancy of patients infected with HIV, which is now treated as a chronic disease requiring lifelong ART treatment. Despite this advance, therapy "fatigue" or discontinuation of components of combination ART remains a serious problem both for the patient's immediate health (progression to AIDS) and for the appearance of new ART-resistant HIV strains.
There is a critical need to deliver and sustain effective levels of ART drug combinations over long periods of time which minimize the challenges in patient adherence due to pill fatigue or side-effects and the requirement of lifelong daily drug intake. A novel combination drug delivery platform that is administered periodically rather than daily and is long-lasting (slow release in physiological contexts) to provide safe and effective use would be an invaluable improvement in HIV therapy.
Technology Overview:The inventors describe a methodology of synthetic polymerization chemistry to create a novel ART polymeric prodrug composed of prodrug monomers (polymer of prodrugs, "POP"). A prodrug is an inactive form of a drug molecule that can be converted to an active compound when exposed to the intended biological context. The invention characterizes polymer-drug conjugates of water-soluble polymeric carriers, biodegradable linkages, and antiviral drug cargos. Conjugated drugs are designed to undergo release via specific linkage bonds (e.g., bio-degradation) from the polymer backbone which could effectively prolong the circulation half-life and alleviate off-target cytotoxic side-effects.
More specifically, therapeutic polymeric carriers degrade to prodrug monomers of nucleoside reverse transcriptase inhibitors (NRTIs) at rates appropriate to match long-acting cabotegravir and rilpivirine dosing frequencies and enable development of complete combination long-acting regimens. This polymeric compound has the planned capacity of carrying multiple antiviral prodrug monomers making it an effective long lasting drug delivery platform (i.e., less frequent dosing) capable of addressing patient pill fatigue while improving the standard of HIV therapy.
Stage of development:In vitro data is available.
PublicationsHobson JJ et al. Nat Commun. 2019 Mar 29;10(1):1413.
