Efficacy and safety of the novel capsid inhibitor lenacapavir to treat multidrug-resistant HIV: week 52 results of a phase 2/3 trial
Issued Date
2023-08-01
Resource Type
eISSN
23523018
Scopus ID
2-s2.0-85166653319
Pubmed ID
37451297
Journal Title
The lancet. HIV
Volume
10
Issue
8
Start Page
e497
End Page
e505
Rights Holder(s)
SCOPUS
Bibliographic Citation
The lancet. HIV Vol.10 No.8 (2023) , e497-e505
Suggested Citation
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., Siripassorn K., Chetchotisakd P., Castagna A., Castelli F., Ronot-Bregigeon S., Molina J.M., Trottier B., Brunetta J., Shirasaka T., Yokomaku Y., Koenig E., Mallolas J., Stellbrink H.J., Hung C.C., Rassool M. Efficacy and safety of the novel capsid inhibitor lenacapavir to treat multidrug-resistant HIV: week 52 results of a phase 2/3 trial. The lancet. HIV Vol.10 No.8 (2023) , e497-e505. e505. doi:10.1016/S2352-3018(23)00113-3 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/88313
Title
Efficacy and safety of the novel capsid inhibitor lenacapavir to treat multidrug-resistant HIV: week 52 results of a phase 2/3 trial
Author(s)
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.
Siripassorn K.
Chetchotisakd P.
Castagna A.
Castelli F.
Ronot-Bregigeon S.
Molina J.M.
Trottier B.
Brunetta J.
Shirasaka T.
Yokomaku Y.
Koenig E.
Mallolas J.
Stellbrink H.J.
Hung C.C.
Rassool M.
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.
Siripassorn K.
Chetchotisakd P.
Castagna A.
Castelli F.
Ronot-Bregigeon S.
Molina J.M.
Trottier B.
Brunetta J.
Shirasaka T.
Yokomaku Y.
Koenig E.
Mallolas J.
Stellbrink H.J.
Hung C.C.
Rassool M.
Author's Affiliation
Siriraj Hospital
Université Paris Cité
IRCCS Istituto Nazionale Malattie Infettive Lazzaro Spallanzani
Yale School of Medicine
Gilead Sciences Incorporated
Faculty of Medicine, Chulalongkorn University
Emory University
Clinique de Médecine Urbaine du Quartier Latin
NewYork-Presbyterian Queens
Central Texas Clinical Research
Université Paris Cité
IRCCS Istituto Nazionale Malattie Infettive Lazzaro Spallanzani
Yale School of Medicine
Gilead Sciences Incorporated
Faculty of Medicine, Chulalongkorn University
Emory University
Clinique de Médecine Urbaine du Quartier Latin
NewYork-Presbyterian Queens
Central Texas Clinical Research
Other Contributor(s)
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 μL 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.