Gilead's Twice-Yearly Long-Acting HIV Therapy Lenacapavir (GS-6207) Meets Primary Endpoint in Phase 2/3 CAPELLA Trial

November 19, 2020 News /BioonBIOON/ -- Gilead Sciences recently announced the top-line results from the Phase 2/3 CAPELLA trial. The trial evaluated the efficacy and safety of lenacapavir (GS-6207) in patients with multidrug-resistant HIV-1 infection who had previously received multiple therapies. The results showed that at the end of the 14-day functional monotherapy period, 88% (n=21/24) of patients in the lenacapavir group achieved a reduction in HIV-1 viral load of at least 0.5 log10 copies/mL, compared to only 17% (n=2/12) of patients in the placebo group.

Lenacapavir is an investigational, first-in-class, novel, selective HIV-1 capsid inhibitor with potent antiviral activity. It rapidly reduces viral load after a single subcutaneous injection and is currently being developed as part of a long-acting regimen, in combination with other antiretroviral agents, for the treatment of HIV-1 infection.

If approved, lenacapavir will become the first HIV capsid inhibitor available for the treatment of HIV-1 infection.In May 2019, the United StatesFDALenacapavir was granted Breakthrough Therapy Designation (BTD), in combination with other antiretroviral agents, for the treatment of heavily treatment-experienced individuals with multidrug-resistant HIV-1 infection.

In the CAPELLA trial, 36 HIV-1–infected adults with resistance to multiple classes of HIV medications and detectable viral load while on a failing regimen were randomized in a 2:1 ratio to receive either oral lenacapavir or placebo for 14 days (functional monotherapy) in addition to continuing their failing regimen. Among the 24 patients randomized to lenacapavir, the median baseline viral load was 4.2 log10 copies/mL, and 67% had CD4 counts below 200 cells/μL. At the end of the 14-day functional monotherapy period, a statistically significantly higher proportion of patients in the lenacapavir group achieved the primary endpoint of at least a 0.5 log10 copies/mL reduction in viral load compared with the placebo group (88% vs 17%, p<0.0001). Furthermore, the mean change in viral load was statistically significantly greater in the lenacapavir group than in the placebo group (−1.93 log10 copies/mL vs −0.29 log10 copies/mL, p<0.0001).

In the study, lenacapavir was generally safe and well tolerated. No serious adverse events related to the study drug were observed during the 14-day period, and no discontinuations of the study drug occurred for any reason, including due to adverse events. The most commonly observed adverse events in this part of the study included injection site swelling (21%) and injection site nodules (17%), the majority of which were Grade 1 or Grade 2 in severity.

Other data from this study will be available in future scientificMeetingpublished above. Following a 14-day functional monotherapy period, all patients received open-label lenacapavir in combination with an optimized background regimen. The maintenance phase of the study will evaluate the efficacy and safety of subcutaneous lenacapavir administered every six months, as well as lenacapavir combined with an optimized background regimen, at Weeks 26 and 52 of treatment.

Edwin DeJesus, MD, Medical Director of the Orlando Immunology Center, stated, “There is an urgent need for innovative treatment options for people living with HIV who have limited therapeutic choices and are unable to maintain virologic suppression on their current regimens, whether due to challenges in adhering to complex therapies or resistance caused by HIV mutations. Preliminary results from the CAPELLA trial demonstrated that lenacapavir rapidly reduced viral load in individuals with multidrug-resistant HIV who had been heavily pretreated. This clinical response may have significant implications for both individual patients and public health.”

Compared with currently available antiretroviral drugs, lenacavivir works in a novel way by blocking the HIV capsid (a structure that surrounds and protects the virusHeredityactivity of proteins (substances and essential enzymes). In in vitro studies, lenacapavir can block multiple distinct stages of the viral life cycle, with the potential to prevent viral infection and contact with uninfected cells.

Currently, the safety, efficacy, and dosing regimen of lenacapavir are being evaluated in multipleClinical Trialsevaluated. In July this year, data from an ongoing Phase I study presented at the 23rd International AIDS Conference (AIDS 2020) supported the use of lenacapavir as a subcutaneous injection administered every six months for the treatment and prevention of HIV. In October, at IDWeek 2020 (the U.S. Conference on Infectious Diseases), Gilead Sciences announced the addition of a new cohort to its HIV prevention study in women, evaluating lenacapavir as an injectable pre-exposure prophylaxis (PrEP) option dosed every six months. Gilead Sciences also plans to initiate another PrEP study of lenacapavir in mid-to-late 2021 among men who have sex with men and transgender women. (Bioon.com)

Original Source: Gilead Announces Investigational Long-Acting HIV-1 Capsid Inhibitor, Lenacapavir, Achieves Primary Endpoint in Phase 2/3 Study in Heavily Treatment-Experienced People Living With HIV