Gilead Submits NDA to FDA for Lenacapavir (GS-6207), a Twice-Yearly Long-Acting Capsid Inhibitor for Multidrug-Resistant HIV-1

June 29, 2021 News /BioonBIOON/ -- Gilead recently announced that it has submitted to the U.S. Food and Drug Administration (FDA) submitted a New Drug Application (NDA) for lenacapavir (GS-6207),This drug is a long-acting HIV-1 capsid inhibitor for the treatment of heavily treatment-experienced (HTE) patients with multidrug-resistant (MDR) HIV-1 infection.Gilead also plans to submit marketing authorization applications for lenacapavir to the European Medicines Agency (EMA) and other global regulatory authorities in the coming months.If approved, lenacapavir will become the first capsid inhibitor and the only HIV-1 treatment regimen administered once every six months.

Lenacapavir is a potential first-in-class long-acting HIV-1 capsid inhibitor. Featuring potent antiviral activity, it rapidly reduces viral load with a single subcutaneous injection. 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 (HTE) patients with multidrug-resistant (MDR) HIV-1 infection. Currently, lenacapavir is being investigated as a subcutaneous injection administered once every six months. It is a potential first-in-class capsid inhibitor for HIV-1 infection, exhibiting no overlapping resistance to currently approved antiretroviral therapies (ART).

Currently, lenacapavir is being developed for use in combination with other antiretroviral drugs for the treatment of multidrug-resistant (MDR) HIV-1 infection in children and adults weighing ≥35 kg who are currently receiving a failing antiretroviral regimen due to resistance, intolerance, or safety concerns.Lenacapavir inhibits HIV-1 replication by interfering with multiple critical steps in the viral life cycle, including capsid-mediated nuclear import of HIV-1 proviral DNA, viral assembly and release, and capsid core formation.

The lenacapavir NDA was supported by data from the Phase 2/3 CAPELLA trial (NCT04150068). This trial evaluated the safety and efficacy of lenacapavir administered via subcutaneous injection every six months in combination with an optimized antiretroviral background regimen. Key data on lenacapavir will be presented at the 11th International AIDS Society (IAS) Conference on HIV Science, held from July 18 to 21, 2021.Meetingpublished on.

Dr. Merdad Parsey, Chief Medical Officer at Gilead Sciences, stated: “Lenacapavir represents a significant breakthrough innovation with transformative potential for patients living with multidrug-resistant HIV who have very limited treatment options. The submission of the NDA for this drug brings us closer to providing an innovative treatment option that helps overcome barriers to achieving viral suppression and addresses the unmet medical needs of this patient population.”

Lenacapavir (GS-6207) Chemical Structure

CAPELLA is a global, multicenter, double-blind, placebo-controlled Phase 2/3 study designed to evaluate the antiviral activity of lenacapavir administered subcutaneously once every 6 months for the treatment of patients with heavily treatment-experienced (HTE) multidrug-resistant (MDR) HIV-1 infection. The trial enrolled men and women with HIV-1 and is currently being conducted at research centers across North America, Europe, and Asia.

In this trial, 36 adults living with HIV-1 who were resistant to multiple classes of HIV-1 drugs and had a detectable viral load while receiving a failing regimen were randomized in a 2:1 ratio to receive oral lenacapavir or placebo for 14 days (functional monotherapy) while continuing their failing regimen. Of the 24 patients randomized to lenacapavir, the median baseline viral load was 4.2 log10 copies/mL, and 67% of patients had a CD4 count <200 cells/μL. The primary endpoint of the study was the proportion of patients achieving a reduction in HIV-1 RNA levels from baseline of ≥0.5 log10 copies/mL at the end of the functional monotherapy period.

Data from the 14-day functional monotherapy phase were presented in March this year at the 2021 Conference on Retroviruses and Opportunistic Infections (CRIO). The results showed that,At the end of the 14-day functional monotherapy period, a statistically significantly higher proportion of patients in the lenacapavir treatment group achieved the primary endpoint of a ≥0.5 log10 copies/mL reduction in viral load compared with the placebo group (88% vs 17%, p<0.0001). Additionally, the mean reduction in viral load was significantly greater in the lenacapavir treatment 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 study drug-related serious adverse events were observed during the 14-day period, and there were no discontinuations of the study drug for any reason, including due to adverse events. The most common adverse events observed in this part of the study included injection site swelling (21%) and injection site nodules (17%), most of which were Grade 1 or 2 in severity.

lenacapavir (GS-6207) Mechanism of Action

Following a 14-day functional monotherapy phase, all patients received open-label lenacapavir in combination with an optimized background regimen. Patients enrolled in the standalone treatment cohort initiated open-label lenacapavir plus an optimized background regimen from Day 1. The maintenance phase of this study is designed to evaluate additional trial endpoints regarding the safety and efficacy of subcutaneous lenacapavir administered every 6 months in combination with an optimized background regimen.

Data through 6 months (26 weeks) have been submitted as part of the NDA toFDA, showing that among patients receiving lenacapavir plus an optimized background regimen, a high virologic suppression rate was maintained through week 26:Among patients who reached Week 26 after the first subcutaneous injection of lenacapavir, 73% (n=19/26) achieved an undetectable viral load (<50 copies/mL).These data will be presented at the upcoming conference. (Bioon.com)

Original Source:Gilead Submits New Drug Application to U.S. Food and Drug Administration for Lenacapavir, an Investigational, Long-Acting Capsid Inhibitor for the Treatment of HIV-1 in People With Limited Therapy Options