Proof-of-Concept Study Shows Positive Results for Novel HIV Treatment

Investigational broadly neutralizing antibody shows promise as potential as a first-in-class treatment option for HIV.

An investigational broadly neutralizing antibody (bNAB), N6LS (VH3810109; GSK), produced positive results in a phase 2a proof-of-concept study.

The experimental treatment is being studied at 2 dosing levels—a high dose and a 10-fold lower dose—in adult patients living with HIV. The study found that a single infusion of N6LS showed strong antiviral efficacy at both dose levels and was well-tolerated by study participants.

bNABs are antibodies that can recognize and inhibit different strains of HIV from entering healthy cells. N6LS acts by binding to a specific site (gp120) on the surface of HIV that stops entry into immune system cells. Preventing HIV from entering human CD4+ cells stops the virus from replicating, thereby helping to inhibit the HIV transmission process.

“Because of the rapidly changing nature of HIV and its potential to develop resistance to certain treatments, the HIV community continues to be in need of medicines with unique mechanisms of action like bNAbs, which may open up a completely new approach to treating HIV,” said Kimberly Smith, MD, MPH, head of Research and Development at ViiV Healthcare, in a press release. “ViiV Healthcare is proud to be at the forefront in advancing this innovative research. These positive proof-of-concept findings show N6LS’s potential as a first-in-class treatment option and underscore our commitment to developing ground-breaking medicines that can help change the way HIV is treated.”

The randomized, multicenter, phase 2a BANNER study evaluated the safety, pharmacokinetics, and antiviral activity of N6LS among 14 treatment-naïve adult patients with HIV. N6LS was also evaluated as monotherapy, with participants administered a single intravenous (IV) infusion of either the 40 mg/kg dose or ~4 mg/kg (280 mg) dose, followed by 48 weeks of standard-of-care antiretroviral therapy.

At the end of the monotherapy period, virologic response to the bNAB was seen in 13 of the 14 patients. The study showed a median viral count decrease from baseline of 1.72 and 1.18 log10 copies/mL for the 40 mg/kg and ~4 mg/kg treatment arms.

N6LS produced a significant drop in viral load that was consistent with antiviral activity found in studies of other bNABs when administered at 40 mg/kg, according to the BANNER trial investigators. Additionally, the reduced viral load and duration of response in the cohort administered the 10-fold-lower dose of ~4 mg/kg exceeded the efficacy found with other bNABs at similarly low doses.

A single IV infusion of N6LS was found to be well-tolerated, with few drug-related adverse events (AEs), none of which led to discontinuation. AEs were reported by 9 participants, all of which were mild or moderate in nature. Only 6 of AEs were considered drug-related and included abdominal pain, gastrointestinal pain, pruritis, asthenia, and myalgia.

“The positive proof-of-concept results presented today show that N6LS was well-tolerated by participants and demonstrated strong antiviral efficacy—even at a low dose—warranting its further study as a potential treatment option for people living with HIV,” BANNER trial investigator Pedro Cahn, MD, scientific director, Fundación Huésped, professor of Infectious Diseases, Buenos Aires University Medical School, said in a press release. “As we investigate bNAbs as an entirely new approach to HIV science, it’s particularly exciting to see that this bNAb exceeded the efficacy reported by other bNAbs at certain low-dosing levels. We look forward to studying this promising medicine further.”

Future studies will include the potential utility of the drug as a long-acting therapeutic option and in approaches for an HIV remission and cure.

REFERENCE

ViiV Healthcare presents positive proof-of-concept findings for N6LS, an investigational, broadly neutralising antibody (bNAb) offering a potential new approach for the treatment of HIV. GSK. October 25, 2022. Accessed October 26, 2022. https://www.gsk.com/en-gb/media/press-releases/viiv-healthcare-presents-positive-proof-of-concept-findings-for-n6ls/