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Long-acting subcutaneous lenacapavir dosed every 6 months as part of a combination regimen in treatment-naïve people with HIV: interim 16-week results of a randomized, open-label, phase 2 induction-maintenance study (CALIBRATE)

Title
Long-acting subcutaneous lenacapavir dosed every 6 months as part of a combination regimen in treatment-naïve people with HIV: interim 16-week results of a randomized, open-label, phase 2 induction-maintenance study (CALIBRATE)
Presenter
Samir Gupta
Authors
S.K. Gupta * (1), M. Berhe (2), G. Crofoot (3), J. Sims (4), P. Benson (5), M. Ramgopal (6), W.E. Sanchez (7), P. Ruane (8), C. McDonald (9), A. Scribner (10), H. Wang (11), L. VanderVeen (11), H. Dvory-Sobol (11), R.H. Hyland (11), M.S. Rhee (11), J.M. Baeten (11), D.M. Brainard (11), E. Koenig (12).
Institutions
(1) Indiana University School of Medicine, Indianapolis, United States, (2) North Texas Infectious Diseases Consultants, Dallas, United States, (3) The Crofoot Research Center, Inc., Houton, United States, (4) St. Hope Foundation, Bellaire, United States, (5) Be Well Medical Center, Berkley, United States, (6) Midway Specialty Care Center, Fort Pierce, United States, (7) Floridian Clinical Research, Hialeah, United States, (8) Ruane Clinical Research Group, Los Angeles, United States, (9) Texas Centers for Infectious Disease Associates, Fort Worth, United States, (10) Diagnostic Clinic of Longview Center for Clinical Research (DCOL), Longview, United States, (11) Gilead Sciences Inc., Foster City, United States, (12) Instituto Dominicano de Estudios Virológicos (IDEV), Santo Domingo, Dominican Republic

BACKGROUND: Lenacapavir (LEN, GS-6207), a potent first-in-class inhibitor of HIV-1 capsid function, is in development as a long-acting agent for treatment and prevention of HIV.
METHODS: CALIBRATE is an ongoing, phase 2, randomized, open-label, active-controlled, induction-maintenance study in treatment-naïve people with HIV-1 (TN-PWH) with CD4+ cell count'¥200/"µL. Participants were randomized (2:2:2:1) to treatment groups (TGs) A to D (Figure). TG-A and B received subcutaneous (SC) LEN with oral daily emtricitabine/tenofovir alafenamide (F/TAF); at W28, those achieving HIV-1 RNA (VL)<50c/mL switched F/TAF to oral daily TAF (TG1) or bictegravir (BIC) (TG2). TG-C received oral daily LEN with F/TAF. TG-D received oral daily B/F/TAF. Primary endpoint is VL<50c/mL at W54 by FDA Snapshot. We report the pre-specified W16 interim efficacy and safety analyses, for which there were no planned statistical comparisons.


RESULTS: 182 participants (7% female, 54% Black) were randomized/dosed (n=52, 53, 52, 25 in TG-A to D). Median age was 29y; 15% had VL>100,000c/mL. At W16, 92% (48/52), 94% (50/53), 94% (49/52), and 100% (25/25) had VL<50c/mL in TG-A, B, C, and D, respectively, by missing=failure, and 98% (48/49), 98% (50/51), 96% (49/51), and 100% (25/25) by missing=excluded. Four participants had VL>50 c/mL: 3 with VL<100c/mL (1 TG-A, 2 TG-C) and 1 with VL>5000c/mL (TG-B). Resistance analysis is ongoing. No participant died, experienced a study drug-related serious adverse event (AE), or discontinued study drug due to AE, and no Grade 3 or 4 AEs were considered study-drug related. Most frequent AEs were injection site erythema, injection site pain (12% each), injection site swelling (11%) and headache (10%). All injection site reactions were mild or moderate.
CONCLUSIONS: LEN, given subcutaneously or orally, in combination with F/TAF led to high rates of viral suppression in TN-PWH by W16. LEN was generally safe and well-tolerated. Results support ongoing evaluation of LEN for treatment and prevention of HIV.