ViiV’s new maturation inhibitor shown safe & effective in Phase IIa study

This week, at CROI 2021, ViiV Healthcare presented data from their Phase IIa ‘Proof of concept’ study into a new investigational maturation inhibitor (GSK3640254) designed to treat HIV in adults.

Maturation inhibitors are a relatively new potential class of HIV treatment, which interrupts the HIV replication life cycle causing the HIV viruses that are created to be ‘immature’ and not pose a threat. It’s this new mechanism that means that a maturation inhibitor treatment would not be affected by resistances to existing classes of HIV treatment.

The Phase IIa trial was divided into two parts to evaluate the antiviral activity, safety, and tolerability of once-daily GSK’254 among 34 treatment-naïve adults living with HIV.

In part one, participants received GSK3640254 10 mg, 200 mg, or a placebo for 10 days. A planned interim analysis showed treatment emergent resistance associated mutations in the 200 mg arm after dosing was complete.

As a result, in part two, participants received GSK3640254 40 mg, 80 mg, 140 mg, or placebo for a shortened period of seven days.

The primary endpoint was the maximum change in plasma HIV-1 RNA during parts one and two while secondary endpoints measured safety, tolerability, and pharmacokinetic (PK) parameters.

At the conclusion of the study, the largest mean changes in viral load were -1.5 log10 and -2.0 log10 copies/ml in the 140 mg and 200 mg groups, respectively.

Treatment with GSK’254 was generally well-tolerated throughout the study. There were no adverse events (AEs) leading to discontinuation and no deaths reported. AEs were reported by 22 (65%) participants, with the most common being headache (n=4).

Christoph Spinner, M.D., Department of Internal Medicine II at Technical University of Munich, Hospital Rechts der Isar, said: “Because of HIV’s tendency to develop resistance to treatment over time, there is a need to improve the number of treatment options available for people living with HIV. The antiviral, safety, and tolerability findings observed in this proof-of-concept study show the potential of this maturation inhibitor and warrant its continued study as an effective new treatment option for people living with HIV.”

ViiV Healthcare has begun the phase IIb study of GSK3640254, to evaluate the efficacy, safety, and tolerability of this maturation inhibitor as part of a combination therapy for treatment naïve adults living with HIV.