NEW ORLEANS -- An experimental antiretroviral agent that works differently than other HIV drugs demonstrated promising safety and antiviral activity in a study of 40 patients with multidrug-resistant virus who need salvage therapy, a researcher said here.
Ibalizumab, a monoclonal antibody, lowered plasma viral load by a mean of 1.1 log when used as functional monotherapy in the first stage of a phase III clinical trial, according to , from Quest Clinical Research in San Francisco.
Action Points
- Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
If the results are confirmed, the drug could be good news for people who cannot be successfully treated using available therapies, said Lalezari, who presented the late-breaking findings at IDWeek, a joint meeting of the (IDSA), the (HIVMA), the (SHEA), and the (PIDS).
"This is not the most potent drug we've seen, but it's pretty good, and in the setting of multidrug resistance it's very good -- maybe the best we have," Lalezari told reporters earlier.
The value of the drug would be in treating patients who no longer benefit from standard antiretroviral therapy, commented , of Brigham and Women's Hospital in Boston.
"Although we have terrific therapies for initial and second-line treatment," Kuritzkes told reporters at an IDWeek press conference, "we've really come to need new treatments for that core group of patients who have resistance to all of the drugs in our armamentarium,"
Ibalizumab (TMB-355) is being developed and is the first biologic medication for HIV. It targets a human protein rather than attacking the virus directly.
The antibody binds to the CD4 protein on the surface of T cells, a molecule HIV uses to enter its target cells. But instead of blocking attachment, Lalezari said, the compound prevents a conformational change in HIV that allows the virus to enter the cell.
"This is different from all the other HIV drugs we use," according to of the University of Pennsylvania in Philadelphia, the HIVMA program chair for IDWeek. "HIV drugs tend to target enzymes of the virus ... this targets the human immune system."
Ibalizumab has been in development for more than a decade. Early studies showed that it has a unique resistance profile and works against HIV that is resistant to older antiretrovirals. It is not metabolized by the liver or kidneys and does not interact with other drugs, Lalezari said.
After the antibody demonstrated modest efficacy in a previous phase II trial, the FDA granted it orphan drug status and a breakthrough therapy designation.
The is evaluating the efficacy of ibalizumab for patients who are not able to maintain an undetectable viral load on their current HIV therapy.
The study enrolled 40 heavily treatment-experienced patients; a quarter had used more than 10 previous antiretrovirals. They had documented resistance to at least one drug from three antiretroviral classes. However, they needed to have at least one active drug available to build an optimized background regimen; for about a third this meant using another investigational agent.
Most study participants were men, more than half were white, the median age was 51, and they had been infected for more than 20 years on average. At the outset they had a median plasma viral load of 100,000 copies of HIV RNA per ml and an average CD4 count of only 160 cells/mm3, with a third having less than 10 cells/mm3.
"A CD4 count below 10 shows how perilous the health of some of these folks was," Lalezari said.
After a 6-day observation period, participants received a 2,000-mg loading dose of ibalizumab as an IV infusion while remaining on their failing regimens, meaning the antibody was essentially used as monotherapy for 7 days.
The primary study endpoint was the number of people with at least a 0.5 log drop in viral load by day 14.
At that time, they were switched to an optimized background regimen determined by resistance testing. They received a lower-dose 800-mg infusion of ibalizumab on day 21 and then every other week until week 23.
Lalezari reported the day 14 data here. Seven days after the initial ibalizumab dose, he said, viral load decreased by an average of 1.1 log. During this monotherapy period, 83% of patients had at least a 0.5 log drop and 60% had a decrease of 1 log or more.
Ibalizumab was generally well tolerated, with no treatment-related serious adverse events or early discontinuations, Lalezari said. The most commonly reported adverse events were dizziness (10%), fatigue (5%), nausea or vomiting (5%), and rash (2.5%).
Lalezari said ibalizumab is the first of what he sees as a trend toward long-acting injectable therapies for HIV. But although its biweekly dosing is appealing, it is expected to fill a niche for difficult-to-treat patients rather than playing a role in first-line therapy.
Although ibalizumab might not have a large market, Lalezari gave credit to the FDA for advancing a new treatment for the small number of people who do not benefit from existing HIV therapies.
Lalezari estimated that less that 5% of HIV patients fall into this category. The number of people who are on treatment but still viremic is somewhere in the thousands, and maybe as high as 10,000, he told 鶹ý.
"By and large the great majority of our HIV patients are doing fine -- this is about the patients who are left behind," Lalezari said. "This group is not large in number, but they are extremely vulnerable."
Disclosures
Lalezari disclosed relevant relationships with AbbVie, Bavarian Nordic, Calimmune, Genocea Biosciences, GlaxoSmithKline, Merck, Sangamo BioSciences, ViiV Healthcare, Arrowhead, Bristol-Myers Squibb, CytoDyn, Gilead Sciences, Janssen, Novira Therapeutics, and TaiMed Biologics
Primary Source
IDWeek
Lalezari J, et al "Primary efficacy endpoint and safety results of ibalizumab in a phase 3 study of heavily treatment experienced oatients with multi-drug resistant HIV-1 infection" IDWeek 2016.