MILAN — Viral suppression was induced in more than half the heavily pretreated HIV patients after 24 weeks of treatment with fostemsavir (ViiV Healthcare), which is one of the new class of entry inhibitors, results from the phase 3 BRIGHTE trial show.
“It’s a welcome change for heavily treatment-exposed patients,” said Max Lataillade, DO, from ViiV Healthcare, here at the 16th European AIDS Conference.
For those patients, “other drugs are not available anymore,” he told Medscape Medical News. “They get the last of what’s available, and those drugs aren’t well tolerated.”
After years of treatment, the virus can become resistant to one, two, or even three classes of antiretroviral drugs, making it difficult for physicians to cobble together a full combination-therapy regimen. And without such a regimen, the virus can continue to replicate, leaving these patients with detectable viral loads and, often, worse outcomes.
Entry Inhibitors
Fostemsavir joins maraviroc, enfuvirtide, and the investigational antiretroviral ibalizumab in the class of drugs known as entry inhibitors. Whereas protease inhibitors and integrase inhibitors block the ability of HIV to proliferate after a target CD4 cell is infected, entry inhibitors target different stages of HIV’s “entry” into CD4 cells.
Previous research has shown there are three steps to entry: attachment to the CD4 cell, binding to coreceptors, and fusion (Curr Opin HIV AIDS. 2009;4:82-87). Fostemsavir is unlike the other entry inhibitors because it binds to the HIV envelope and blocks its ability to access the CD4 cell in the first place.
It’s the first time I feel that we’re actually attacking the virus itself.
“It prevents attachment, which is the first step of any infection,” Dr Lataillade explained. “It’s the first time I feel that we’re actually attacking the virus itself.”
The BRIGHTE Study
First, 272 people with HIV, sensitivity to one or two classes of drug, and a viral load of at least 400 copies/mL were randomized to receive, in addition to their current regimen, twice-daily fostemsavir 600 mg or placebo.
Eight days later, 99 participants who were resistant to every class of drug were added to the study.
Thereafter, this second cohort of all 371 participants received open-label twice-daily fostemsavir 600 mg in addition to an optimized background regimen.
At baseline, CD4 counts were below 50 cells/μL in 41% of the participants, and below 200 cells/μL in 72%.
The study is ongoing, but Dr Lataillade presented 24-week data.
At day 8, the reduction in viral load in the first cohort was significantly greater in the fostemsavir group than in the placebo group (0.79 log10 vs 0.17 log10 cells/mL; P < .0001).
At week 24, 54% of patients in the second cohort had achieved viral suppression.
Also by week 24, 71 patients had withdrawn from the study — 45 from the first cohort and 26 from the second. The rate of withdrawal because of ineffectiveness was similar in the first and second cohorts (3% vs 4%). The other reasons for withdrawal were adverse events, loss to follow-up, pregnancy, and death.
In the second cohort, 91% of the patients experienced adverse events, including headache, diarrhea, and nausea. However, only one-third of the adverse events — primarily pneumonia — were severe. Of the 17 deaths that occurred during the study period, 12 were from AIDS-defining illnesses, immune reconstitution inflammation syndrome, or acute infection related to HIV.
The fostemsavir data were what Roy Gulick, MD, from the Weill Medical College of Cornell University in New York City, had been most looking forward to at the conference.
He has a patient who has become resistant to every drug he has taken. “He’s out of options,” Dr Gulick told Medscape Medical News.
He said he is concerned, however, that if treatment has previously failed because the patient was not adherent, even a drug with a new mode of action might not be effective.
“I hate to put such patients on a new drug and have them just get nonadherent again,” Dr Gulick said.
There’s still a business case to develop drugs with new modes of action, if only for the principle of innovative thinking.
It is exciting to see that “there’s still a business case to develop drugs with new modes of action, if only for the principle of innovative thinking,” said Jens Lundgren, MD, DMSc, from the University of Copenhagen.
This is not simply the reformulation of an existing drug; “this is actually something new,” he emphasized. Although he did add that reformulation can be a good strategy, as was seen with tenofovir alafenamide.
The BRIGHTE study was funded by ViiV Healthcare. Dr Lataillade is an employee of ViiV Healthcare. Dr Lundgren and Dr Gulick have disclosed no relevant financial relationships.
16th European AIDS Conference: Abstract PS8/5. Presented October 27, 2017.
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