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)


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.