Background Lenacapavir, a first-in-class HIV-1 capsid inhibitor, is in development as a long-acting agent for treating and preventing HIV-1. We aimed to evaluate the efficacy and safety of lenacapavir with an optimised background regimen in adults living with multidrug-resistant HIV-1 up to 52 weeks. Methods This ongoing, international, phase 2/3 trial at 42 sites included adults living with multidrug-resistant HIV-1. In cohort 1, 36 participants were randomly assigned (2:1) to add oral lenacapavir (600 mg, days 1 and 2; 300 mg, day 8) or placebo to an existing failing regimen. At day 15, those on oral lenacapavir received subcutaneous lenacapavir 927 mg every 26 weeks; those on placebo started lenacapavir (2-week oral lead-in then subcutaneous). Cohort 1 started an optimised background regimen on day 15. In cohort 2 (non-randomised), 36 participants started an optimised background regimen concurrent with lenacapavir (oral to subcutaneous). Here we report the secondary endpoints of plasma HIV-1 RNA of less than 50 copies per mL or less than 200 copies per mL at week 52 (US Food and Drug Administration snapshot algorithm) in cohort 1 along with results for cohorts 1 and 2 combined. This trial is registered with ClinicalTrials.gov, NCT04150068, and clinicaltrialregister.eu, EudraCT 2019-003814-16 and is ongoing. Findings Of 72 participants, 46 (64%) had CD4 counts of less than 200 cells per & mu;L and 38 (53%) had no more than one fully active antiretroviral drug at baseline. In cohort 1, 30 of 36 participants (83%, 95% CI 67-94) had less than 50 HIV-1 RNA copies per mL and 31 of 36 participants (86%, 71-95) had less than 200 HIV RNA copies per mL, at week 52. In all, nine participants (four in cohort 1, five in cohort 2) had emergent lenacapavir resistance; four resuppressed (HIV-1 RNA <50 copies per mL) while maintaining lenacapavir use. One participant discontinued study drug owing to injection site reaction. Interpretation In participants with multidrug-resistant HIV-1, subcutaneous lenacapavir in combination with an optimised background regimen resulted in a high rate of virological suppression up to 52 weeks. Funding Gilead Sciences. Copyright & COPY; 2023 Published by Elsevier Ltd. All rights reserved.
Efficacy and safety of the novel capsid inhibitor lenacapavir to treat multidrug-resistant HIV: week 52 results of a phase 2/3 trial / Ogbuagu, O.; Segal-Maurer, S.; Ratanasuwan, W.; Avihingsanon, A.; Brinson, C.; Workowski, K.; Antinori, A.; Yazdanpanah, Y.; Trottier, B.; Wang, H.; Margot, N.; Dvory-Sobol, H.; Rhee, M. S.; Baeten, J. M.; Molina, J. M.; Molina, J. M.; Molina, J. M.; Dejesus, E.; Richmond, G. J.; Berhe, M.; Ruane, P. J.; Sinclair, G. I.; Lichtenstein, K.; Ramgopal, M. N.; Wiznia, A.; Workowski, K.; Sanchez, W.; Brinson, C.; Mcgowan, J. P.; Creticos, C. M.; Berger, D. S.; Wheeler, D. A.; Hagins, D.; Crofoot, G. E.; Sims, J.; Osiyemi, O.; Hodge, T.; Zurawski, C.; Ogbuagu, O.; Segal-Maurer, S.; Ratanasuwan, W.; Avihingsanon, A.; Siripassorn, K.; Chetchotisakd, P.; Castagna, A.; Antinori, A.; Castelli, F.; Ronot-Bregigeon, S.; Molina, J. M.; Yazdanpanah, Y.; Trottier, B.; Brunetta, J.; Shirasaka, T.; Yokomaku, Y.; Koenig, E.; Mallolas, J.; Stellbrink, H. J.; Hung, C. C.; Rassool, M.. - In: THE LANCET. HIV. - ISSN 2352-3018. - 10:8(2023), pp. 497-505. [10.1016/S2352-3018(23)00113-3]
Efficacy and safety of the novel capsid inhibitor lenacapavir to treat multidrug-resistant HIV: week 52 results of a phase 2/3 trial
Castagna A.;
2023-01-01
Abstract
Background Lenacapavir, a first-in-class HIV-1 capsid inhibitor, is in development as a long-acting agent for treating and preventing HIV-1. We aimed to evaluate the efficacy and safety of lenacapavir with an optimised background regimen in adults living with multidrug-resistant HIV-1 up to 52 weeks. Methods This ongoing, international, phase 2/3 trial at 42 sites included adults living with multidrug-resistant HIV-1. In cohort 1, 36 participants were randomly assigned (2:1) to add oral lenacapavir (600 mg, days 1 and 2; 300 mg, day 8) or placebo to an existing failing regimen. At day 15, those on oral lenacapavir received subcutaneous lenacapavir 927 mg every 26 weeks; those on placebo started lenacapavir (2-week oral lead-in then subcutaneous). Cohort 1 started an optimised background regimen on day 15. In cohort 2 (non-randomised), 36 participants started an optimised background regimen concurrent with lenacapavir (oral to subcutaneous). Here we report the secondary endpoints of plasma HIV-1 RNA of less than 50 copies per mL or less than 200 copies per mL at week 52 (US Food and Drug Administration snapshot algorithm) in cohort 1 along with results for cohorts 1 and 2 combined. This trial is registered with ClinicalTrials.gov, NCT04150068, and clinicaltrialregister.eu, EudraCT 2019-003814-16 and is ongoing. Findings Of 72 participants, 46 (64%) had CD4 counts of less than 200 cells per & mu;L and 38 (53%) had no more than one fully active antiretroviral drug at baseline. In cohort 1, 30 of 36 participants (83%, 95% CI 67-94) had less than 50 HIV-1 RNA copies per mL and 31 of 36 participants (86%, 71-95) had less than 200 HIV RNA copies per mL, at week 52. In all, nine participants (four in cohort 1, five in cohort 2) had emergent lenacapavir resistance; four resuppressed (HIV-1 RNA <50 copies per mL) while maintaining lenacapavir use. One participant discontinued study drug owing to injection site reaction. Interpretation In participants with multidrug-resistant HIV-1, subcutaneous lenacapavir in combination with an optimised background regimen resulted in a high rate of virological suppression up to 52 weeks. Funding Gilead Sciences. Copyright & COPY; 2023 Published by Elsevier Ltd. All rights reserved.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
