Efficacy and safety of the novel capsid inhibitor lenacapavir to treat multidrug-resistant HIV: week 52 results of a phase 2/3 trial.
Journal
The lancet. HIV
ISSN: 2352-3018
Titre abrégé: Lancet HIV
Pays: Netherlands
ID NLM: 101645355
Informations de publication
Date de publication:
08 2023
08 2023
Historique:
received:
02
02
2023
revised:
03
05
2023
accepted:
04
05
2023
medline:
7
8
2023
pubmed:
15
7
2023
entrez:
14
7
2023
Statut:
ppublish
Résumé
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. 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. 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. 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. Gilead Sciences.
Sections du résumé
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.
Identifiants
pubmed: 37451297
pii: S2352-3018(23)00113-3
doi: 10.1016/S2352-3018(23)00113-3
pii:
doi:
Substances chimiques
Pyridones
0
Anti-HIV Agents
0
RNA
63231-63-0
Banques de données
ClinicalTrials.gov
['NCT04150068']
EudraCT
['2019-003814-16']
Types de publication
Randomized Controlled Trial
Clinical Trial, Phase III
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e497-e505Investigateurs
Edwin DeJesus
(E)
Gary J Richmond
(GJ)
Mezgebe Berhe
(M)
Peter J Ruane
(PJ)
Gary Ian Sinclair
(GI)
Kenneth Lichtenstein
(K)
Moti N Ramgopal
(MN)
Andrew Wiznia
(A)
Kimberly Workowski
(K)
William Sanchez
(W)
Cynthia Brinson
(C)
Joseph P McGowan
(JP)
Catherine M Creticos
(CM)
Daniel S Berger
(DS)
David A Wheeler
(DA)
Debbie Hagins
(D)
Gordon E Crofoot
(GE)
James Sims
(J)
Olayemi Osiyemi
(O)
Theo Hodge
(T)
Christine Zurawski
(C)
Onyema Ogbuagu
(O)
Sorana Segal-Maurer
(S)
Winai Ratanasuwan
(W)
Anchalee Avihingsanon
(A)
Krittaecho Siripassorn
(K)
Ploenchan Chetchotisakd
(P)
Antonella Castagna
(A)
Andrea Antinori
(A)
Francesco Castelli
(F)
Sylvie Ronot-Bregigeon
(S)
Jean-Michel Molina
(JM)
Yazdan Yazdanpanah
(Y)
Benoit Trottier
(B)
Jason Brunetta
(J)
Takuma Shirasaka
(T)
Yoshiyuki Yokomaku
(Y)
Ellen Koenig
(E)
Josep Mallolas
(J)
Hans-Jurgen Stellbrink
(HJ)
Chien-Ching Hung
(CC)
Mohammed Rassool
(M)
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2023 Elsevier Ltd. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests OO has received consulting fees from Gilead Sciences, ViiV Healthcare, and Janssen Pharmaceuticals, and speaking honoraria from Gilead Sciences. SS-M has received consulting fees and speaking honoraria from Gilead Sciences and Janssen Therapeutics and travel support from Gilead Sciences. AAv has received support for this article from Gilead Sciences; research grants from MSD, ViiV–GSK, Viatris, and Pfizer; speaking honoraria from Gilead Sciences, ViiV–GSK, and Viatris; and travel support from Gilead Sciences. KW has received research or grant support from Gilead Sciences and AbbVie. AAn has received consulting fees from Gilead Sciences, ViiV Healthcare, Janssen-Cilag, Roche, GSK, Pfizer, AstraZeneca, and Merck; grant or research support from Gilead Sciences and ViiV Healthcare; speaking honoraria from Gilead Sciences, Merck, GSK, Moderna, Pfizer, and ViiV Healthcare; and travel support from Gilead Sciences. CB has received consulting fees and speaking honoraria from Gilead Sciences and ViiV Healthcare. BT has received consulting fees and speaking honoraria from Gilead Sciences, Merck, and ViiV Healthcare and travel support from Gilead Sciences and ViiV Healthcare. J-MM has served on boards for Aelix; received consulting fees from Gilead Sciences, ViiV, and Merck; received grant or research support from Gilead Sciences; and received payment for expert testimony from Merck. HW, NM, HD-S, MSR, and JMB are employees of Gilead Sciences and hold stock interest in the company. WR and YY declare no competing interests.