Strong trial results and high resistance barrier for integrase inhibitor treatment put Gilead on path to new HIV drug
Drug trial results for new integrase inhibitor show promising viral suppression rates at the Conference for Retroviruses and Opportunistic Infections (CROI).
A newly-developed integrase inhibitor could form part of a powerful, safe and highly effective new combination drug to treat HIV, according to the promising results of a clinical phase II trial of 98 patients.
American biopharmaceutical group Gilead Sciences presented the results of its latest study into bictegravir, an integrase strand transfer inhibitor (INSTI) which has a high barrier to resistance, at this week’s Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle.
The study evaluated bictegravir over a 48-week period in combination with two other drugs, emtricitabine (FTC) and tenofovir alafenamide (TAF), which is the most common nucleoside reverse transcriptase inhibitor (NRTI) combination.
In results which could ramp up the rivalry between the two pharmaceutical giants, bictegravir equalled the suppression achieved by London-based GlaxoSmithKline’s widely-used dolutegravir integrase inhibitor. Bictegravir achieved viral suppression among 97% of the participants at both the halfway point and end of the trial, while dolutegravir recorded 94% suppression at 24 weeks and 91% after 48 weeks.
Bictegravir was found to produce a 100-fold reduction in viral load in people living with HIV, with none of the patients discontinuing because of kidney problems, which can be an issue in HIV treatment.
Importantly, bictegravir proved potent against both wild-type and most INSTI-resistant strains of HIV in vitro. In the trial, neither patients on bictegravir nor dolutegravir had INSTI or NRTI-resistant mutations after 48 weeks.
Bictegravir has an advantage over Gilead’s older integrase inhibitor, elvitegravir, in that it does not require a booster drug to be administered. If it reaches the market, it will be prescribed as a single-pill combination with FTC and TAF, and the trial suggests its dose could range from 5mg to 100mg in people living with HIV. Phase III trials have already begun assessing this fixed dose combination.
INSTIs are an increasingly important feature of initial antiretroviral therapy (ART), and their high potency and tolerability means they are included in most regimens for first-line treatment of HIV in Europe and the US.
The study could result in a new drug being made available in 2018 if the next phases of testing are successful.