Three weeks after Gilead filed its long-acting HIV drug for FDA approval, the new antiviral is padding its case.
After six months, lenacapavir, along with other antiretroviral drugs, drove HIV down to undetectable levels in 81% of 36 patients in a phase 3 study. Gilead tested the drug in patients with HIV-1 whose treatments were no longer working.
“The patients in this study are the individuals who have taken many medications. The average number of years since HIV diagnosis was 24 and the average number of prior antiretroviral therapy was 11,” said Jared Baeten, M.D., Ph.D., vice president of clinical research at Gilead. “These are individuals who have tried for many years to control their HIV successful and have probably succeeded and failed at times. Now they are at a place where they were not succeeding and nearing the end of options available to them.”
The data were presented virtually at the International AIDS Society Conference on HIV Science.
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There are many antiretroviral drugs approved for the treatment of HIV that effectively keep the virus at very low levels. However, the virus tends to mutate and can evade these drugs. If a patient’s virus becomes resistant to one type of drug, such as a protease inhibitor, it may become partially or fully resistant to other drugs in that class.
Enter lenacapavir, a capsid inhibitor that works differently than approved antiretrovirals and doesn’t have any overlapping resistance with them. It works by targeting the capsid, the protein shell that holds the virus together, weakening this shell and “busting it open,” Baeten said.
“It doesn’t allow the virus to transmit its material into a new cell,” Baeten added, which blocks replication.
The capsid is an attractive target because the RNA that encodes it is fairly stable, so disrupting the shell could attack HIV without running the risk that it will mutate and quickly become resistant to the treatment.
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No patients quit the study because of side effects, the most common of which were injection site reactions, such as swelling and redness, affecting about a quarter of patients. Four patients developed resistance to lenacapavir, but three of them later saw their HIV levels go down.
“It’s really striking that three of the individuals resuppressed, including two of those three without a change to the rest of their regimen... Because lenacapavir has a novel mechanism of action, the development of resistance to lenacapavir doesn’t inhibit the ability of individuals to take other agents,” Baeten said.
Gilead is developing lenacapavir for the treatment and prevention of HIV, and it is working on both oral and injected versions of the drug. The phase 3 study, dubbed CAPELLA, is studying the injected version given every six months.
Of the 36 trial participants, two-thirds received oral lenacapavir and one-third received a placebo for 14 days. When the two weeks were up, all patients started receiving the injectable form of lenacapavir. Another group of 36 patients received open-label lenacapavir along with other antiretroviral drugs from day 1.
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“The CAPELLA results are exciting as they demonstrate that an undetectable viral load is achievable in a patient population that has typically had challenges with viral suppression over the course of their journey living with HIV,” said Jean-Michel Molina, M.D., of the University of Paris and the Saint-Louis and Lariboisière Hospitals, who presented the data. “New, long-acting options in development, like lenacapavir, are critical to changing the clinical landscape.”
Adding a new, long-acting drug to the arsenal against HIV could make it easier for people to stick to their treatment.
“Long-acting agents offer real potential for impacting the course of the epidemic. Globally, a third of individuals—maybe even more—are not achieving viral suppression … Some of that is due to struggles with adherence to antiretroviral therapy,” Baeten said.
As it continues developing lenacapavir for different types of HIV patients, including people who have never been treated for HIV, Gilead is working with Merck to combine their long-acting treatments. The duo partnered in March to combine lenacapavir with Merck’s islatravir, as well as with another type of HIV drug called integrase inhibitors.
The companies are sharing commercialization costs 60-40. Gilead will take the lead on commercializing oral medicines in the U.S., while Merck will do so in the rest of the world. These responsibilities will be flipped for injectable drugs.