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GLASGOW, Scotland -- Novel investigational agent fostemsavir, in combination with optimized background therapy, maintained virologic response in heavily pretreated HIV patients at week 48, a researcher said here.

Rates of virologic suppression (<40 copies/mL) were maintained from week 24 to week 48, and were 54% for a randomized cohort of patients, and 38% for a separate non-randomized cohort, reported Peter Ackerman, MD, of ViiV Healthcare in Branford, Connecticut.

Notably, the data also showed higher rates of virologic suppression among patients who were women, black, or older -- subgroups that have often been poorly represented in HIV drug trials.

In a late-breaking presentation of the ongoing phase III study at HIV Glasgow: The International Congress on Drug Therapy in HIV Infection, Ackerman described fostemsavir as a "first-in-class inhibitor prodrug" developed specifically for HIV-infected heavily treatment experienced patients, "a marginalized subpopulation of high unmet medical need," he said.

Fostemsavir also has "a unique resistance profile, with no in vitro cross-resistance to other antiretroviral classes," he said. He explained part of the mechanism of action, where "temsavir locks gp120 in a closed state, preventing the conformational change necessary for CD4 attachment." Viruses thus trapped are then cleared by the host immune system, he said.

The BRIGHTE study examined heavily treatment-experienced patients failing on their current therapies and unable to complete a viable regimen with the remaining fully active agents, Ackerman said.

There were two cohorts. One included patients on one or two fully active agents at enrollment. These were randomized 3:1 to receive the blinded drug or placebo in addition to their failing therapy. After eight days, they were started on the open label drug, plus an optimized background therapy of the investigator's choosing.

The other cohort included patients who Ackerman said served as a "compassionate use" arm and were not randomized. These were heavily treatment-experienced, but had "zero fully active and approved antiretroviral therapy [choices] remaining at the study start." They were started on the drug and optimized background therapy on day 1.

"One of the very unique features of this trial is that non-randomized patients were allowed to co-enroll in other investigational ART trials," Ackerman said.

There were 272 patients (215 patients ongoing) in the randomized cohort, with 99 (67 patients ongoing) in the non-randomized cohort. Median age of all treated participants was 49, almost 80% were men and almost 70% were white. Not surprisingly, two-thirds had HIV-1 RNA of 1,000 to <100,000 copies/mL. In the non-randomized cohort, 86% of patients had a prior history of overt AIDS. In the randomized cohort, half of patients had one "fully active and available antiretroviral agent in initial background therapy," while 43% had two of these agents. In the non-randomized cohort, about 80% of patients had zero active agents available to them, and 15 patients were co-enrolled in another investigational ART trial.

In the randomized cohort, 69% of patients had viral load <200 copies/mL, with 43% in the non-randomized cohort.

"Rates of virologic suppression were essentially identical to what we saw at week 24, which is quite remarkable in this complex, difficult-to-treat patient population," Ackerman said.

In an observed analysis, 62% of patients in the randomized cohort who remained on therapy through week 48 had a viral load of <400 copies/mL, while 85% had a viral load of <200 copies/mL.

The authors noted that CD4+ T-cell counts continued to increase, with a mean change from baseline of +139 cells/μL in the randomized cohort and +63 cells/μL in the non-randomized cohort.

In the subgroup analysis, virologic suppression in the randomized cohort was higher among adults age ≥50, women, and blacks:

• 59% age ≥50 versus 51% age <35
• 81% women versus 51% men
• 65% black versus 50% white

Examining safety, about 92% of participants had at least one adverse event, the authors said, though most were grades 1 or 2. Serious adverse events occurred in 31% of the randomized cohort, but few were considered treatment-related, and only 5% had such events leading to discontinuation. There were 11 deaths in the randomized cohort and 14 in the non-randomized cohort. The most common adverse event leading to discontinuation was infection.

Ackerman concluded that these results from the ongoing study "support further development of [fostemsavir] as a therapeutic option" for this population, with multi-drug resistance and few remaining active therapies.