Maturation inhibitor shown to be safe and effective in Phase II HIV trial

ViiV Healthcare has presented positive data from its Phase IIa proof-of-concept study evaluating GSK3640254 (GSK’254), an investigational maturation inhibitor being developed to combat HIV. In the trial, GSK’254 was safe, well-tolerated and showed antiretroviral activity, with the highest doses (140mg and 200mg) showing the greatest reduction in plasma HIV-1 RNA. The findings were presented at the virtual 2021 Conference on Retroviruses and Opportunistic Infections (CROI).

Maturation inhibitors are a class of antiretroviral medicines that prevent HIV replication by inhibiting the protease-mediated cleavage of the HIV structural protein (Gag) in the late stage of the viral life cycle. This causes the formation of immature virus particles. As maturation inhibitors use a different mechanism of action to other antiretrovirals currently available, they have the potential to offer new treatment options for individuals who may have experienced resistance to existing treatments.

Dr Kimberly Smith, Head of Research & Development at ViiV Healthcare, commented: “It is not uncommon for individuals to experience a treatment failure over the course of their lifetime with HIV, making medicines that use new mechanisms of action to treat HIV essential in our efforts to end this epidemic. Because there are no treatments available that target this specific stage of the HIV life cycle, maturation inhibitors may help meet a critical need, particularly for individuals who are treatment experienced. These positive proof-of-concept findings show the potential of GSK’254 and underscore our commitment to researching and developing a broad range of innovative approaches to treating HIV.”

The Phase IIa study (NCT03784079) had two parts and was adaptive in design. Its primary endpoint was to evaluate the antiviral efficacy of once-daily GSK’254 by measuring maximum change from baseline in plasma HIV-1 RNA, the secondary endpoints were assessing the safety and tolerability of once-daily GSK’254 and based on adverse events and changes in haematology parameters.

The trial enrolled 34 treatment-naïve adults living with HIV. In part one, participants received GSK’254 10mg, 200mg or placebo for 10 days. A planned interim analysis showed treatment emergent resistance associated mutations in the 200mg arm after dosing was complete. As a result, in part two, participants received GSK’254 40mg, 80mg, 140mg or placebo for a shortened period of seven days.

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, with no adverse events leading to discontinuation and no deaths reported. Overall, adverse events were reported by 22 (65 percent) participants, with the most common being headache (occurring in four).

Dr Christoph Spinner, Department of Internal Medicine II at Technical University of Munich, Hospital Rechts der Isar, Germany, 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 has begun the Phase IIb study of GSK’254, to evaluate the efficacy, safety and tolerability of this maturation inhibitor as part of a combination therapy for treatment naïve adults living with HIV.

ViiV Healthcare is a is a global specialist HIV company established in November 2009 by GlaxoSmithKline and Pfizer. GSK is the majority owner and Pfizer and Shionogi Limited are stakeholders.