CROI 2022: Lenacapavir: 54 week results in treatment-naive participants of CALIBRATE study
1 March 2022. Related: Conference reports, Antiretrovirals, CROI 29 (Retrovirus) 2022.
Samir Gupta from Indiana University presented 54-week results on the capsid inhibitor lenacapavir in 182 treatment-naive individuals in the randomised phase 2 CALIBRATE study. 
The study design included randomisation to one of four open-label once-daily groups (2:2:2:1), with differences in the three maintenance combinations at week 28 (Q6M LEN injections +TAF, Q6M LEN injections + bictegravir or oral LEN+F/TAF) compared to a control group of bictegravir/F/TAF (n=25); groups 1, 2, 3, and 4 respectively). 
Interim results were reported at IAS last year  and 92% of participants subsequently achieved viral suppression at week 28.
Baseline characteristics previously reported included median age 29 years (range: 19 to 72), 93% men (7% women), 52% black, 45% Hispanic/Latinx. Median viral load and CD4 count at baseline were 4.3 log copies/mL (IQR: 3.8 to 4.7) with 15% >100,000 c/mL and 437 cells/mm3 (IQR: 332 to 599), with only two participants <200 cells/mm3.
The primary endpoint of viral efficacy (<50 copies/mL) was reported for 90%, 85%, 85% and 92% for groups 1, 2, 3, and 4 respectively. Viral failure was reported for 4%, 4%, 6% and 0 of the same groups, with remaining participants having missing data.
Six participants met criteria for resistance testing (1, 1, 3 and 1 in groups 1 to 4 respectively), two with resistance to lenacapavir. One participant in group 2 developed Q57H + K70R in capsid at week 10 (20-fold resistance) and one in group 3 developed Q57H alone at week 54 (7-fold). Both were reported in the context of likely low adherence to oral ART and both resuppressed using combinations of an INSTI and two NRTIs.
Lenacapavir generated similar early rapid viral suppression as the integrase inhibitor-based control group. Minimal data was provided on CD4 count other than similar average increases of about 200 cells/mm3 in each arm.
Tolerability was generally good and similar to oral control with headache 13% vs 12%, nausea 13% vs 4% and COVID-19 10% vs 12%, all in combined LEN vs control, respectively. There were no serious AE’s related to lenacapavir, or discontinuations, other than to injection site reactions (ISRs).
ISRs were common (approximately 15% after injection 1 and 12% after injection 2, but were mainly grade 1 or 2 and caused only three participants to discontinue (all grade 1). However, nodules or hard skin persisted for over six months (median 195 and 202 days for nodules and induration respectively).
There were no clinically relevant or grade 3/4 lab abnormalities.
Other studies on lenacapavir including Week 48 results in treatment experienced participants in the CAPELLA study and use as PrEP are reported in a separate HTB report. 
Lenacapavir is currently on clinical hold related to a technical concern about glass vials used in these studies.
A press statement from Gilead outlines further details to resolve this. 
- Gupta S et al. Lenacapavir as part of a combination regimen in treatment naive PWH: week 54 results. CROI 2022. 12-16 February 2022, virtual. Oral abstract 138.
- ClinicalTrials.gov. Study to evaluate the safety and efficacy of lenacapavir in combination with other antiretroviral agents in people living with HIV (CALIBRATE).
- IAS 2021: lenacapavir studies show impressive results in naive, extensive drug resistance and potential as PrEP. IAS 2021 reports. HTB (1 August 2021).
- Lenacapavir at CROI 2022: 6-monthly dosing in treatment-experienced participants, and as PrEP in macaques. CROI 2022 reports. HTB (1 March 2022).
- Gilead press statement. Gilead receives complete response letter from US FDA for investigational lenacapavir due to vial compatability issues. (1 March 2022).
This report was first published on 19 February 2022.