People with HIV (PWH) who experience multidrug resistance (MDR) have limited or no therapy options, which can leave their disease management very challenging.
One therapy option for these patients is lenacapavir (Sunlenca). This HIV antiretroviral (ARV) was FDA approved in late 2022 for adult patients living with HIV, whose infections cannot be successfully treated with other available treatments due to resistance, intolerance, or safety considerations.
The approval was based around the data from the CAPELLA study, which was a double-blinded, placebo-controlled global multicenter trial designed to evaluate lenacapavir when administered every 6 months as a subcutaneous injection in heavily treatment-experienced (HTE) people with MDR.
Lenacapavir is the first of a new class of therapies called capsid inhibitors to be FDA-approved for treating HIV. This antiretroviral works by blocking the HIV-1 virus’ protein shell (the capsid), thereby interfering with multiple essential steps of the viral lifecycle.
For its therapy regimen, Lenacapavir’s starting protocol is for patients to be given as oral tablets and subcutaneous injections, followed by maintenance treatments administered as single injections every 6 months. Lenacapavir is part of a regimen in combination with other antiretroviral(s).
At this week’s ongoing Conference on Retroviruses and Opportunistic Infections (CROI) in Denver, CO, new data was presented as a poster on the antiviral from the CAPELLA study.
Specifically, the results demonstrated treatment benefits over a 2-year period. “In HTE PWH with MDR or an optimized background regimen (OBR) with no fully active ARVs, [lenacapavir] led to sustained virologic suppression over 104 weeks for most participants,” the investigators wrote.
Study Parameters
Specifically, for the results reported at CROI, the data was from the phase 2/3 CAPELLA study, which enrolled people with HIV with HTE. Eligible participants had resistance to ≥2 ARVs in ≥3 of the 4 main ARV classes (NRTI, NNRTI, PI, INSTI).
After initial oral loading, lenacapavir was administered subcutaneously every 6 months.
The OBR participants were selected by individual clinicians, and other investigational drugs were permitted for the study.
The investigators wrote that the OBR overall susceptibility score was the sum of susceptibility scores for each OBR ARV; 0 (no susceptibility), 0.5 (partial susceptibility) and 1 (full susceptibility) and efficacy was assessed at Weeks 26, 52, and 104. Lenacapavir and OBR ARV resistance analyses were done at virologic failure (virologic rebound ≥50 copies/mL or <1 log10 decline vs baseline).
There were 72 patients enrolled, and of them, 12 (17%) had no fully active antiretrovirals in their OBR; 6 of 12 and 1 of 12 had 1 or 2 partially active (score 0.5 each) ARVs, respectively. The investigators report the median (range) number of OBR ARVs was 4 (2–6). Overall, OBR comprised NRTI (9 participants), INSTI (8), PI (7) or NNRTI (6); 5, 2, and 2 participants were on a CD4 post-attachment inhibitor (ibalizumab), CCR5 inhibitor (maraviroc), or attachment inhibitor (fostemsavir), respectively.
“Eight participants had HIV-1 RNA <50 copies/mL at all 3 visits (W26, 52, and 104), including 1 participant with LEN resistance (R; M66I) at W10 and an OBR change at W25. One participant with missing W104 data was suppressed at a later visit; 1 participant not suppressed at W26 developed LEN-R (M66I) but was suppressed at W52 and 104 (OBR changed at W25); and 2 participants had HIV-1 RNA ≥50 copies/mL throughout, but with a stable, low level viral load (1 with <600 copies/mL, OBR changed at W30; 1 with <3000 copies/mL despite emerging LEN-R at W4 [M66M/I]),” the investigators wrote.
Of the 12 study participants, none discontinued the study’s therapy.
More data on this antiviral will be reported at CROI.
Reference
Ogbuagu O, Ratanasuwan W, Avihingsanon A, et al. Lenacapavir Efficacy IN CAPELLA Patients With No Fully Active Agents In Optimized Background Regimen. Poster #630 presented at CROI 2024. March 3-6, 2023. Denver, CO.
