Once-weekly oral ART: islatravir plus lenacapavir 48 week results in phase 2 switch study

Glasgow 2024 included additional 48-week results from a randomised placebo-controlled phase 2 switch study comparing once-weekly islatravir plus lenacapavir (ISL+LEN) to a control group who continued on bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF). [1]

This extended data from a phase 2 study out to 48 weeks: earlier 24 week results having been presented at CROI earlier this year. [2]

This study randomised 104 participants (1:1) on stable ART to either change to islatravir (2 mg) plus lenacapavir (300 mg) or remain on daily bictegravir/F/TAF with appropriate placebo in each arm.

At 24 weeks 49 (94.2%) vs 48 (92.3%) participants were undetectable, in the ISL+LEN vs control groups. No data was available for 2 vs 4 pts respectively. One VL increase to 251 copies/mL) resuppressed without changing ART. No rebounds were seen with B/F/TAF.

New data at Glasgow reported continued high levels of efficacy continued between weeks 24 and 48. Secondary endpoint results were also presented.

Baseline characteristics included median age 40 (range: 26 to 76), just over 80% were cisgender men, with almost 20% cisgender women, one transgender woman and one non-binary participant; 50% were white, 35% Black and 30% were Latinx. Mean CD4 was 786 cells/mm³ (SD+/–250) with median BMI 27.1 (IQR: 24.5 to 29.4).

Viral response <50 copies/mL remained the same at week 48 with 49 (94.2%) vs 48 (92.3%) participants remaining undetectable. Three participants in each arm discontinued the study due to reasons unrelated to the study drugs had done this when viral load was undetectable, with an additional participant in the BIC/F/TAF arm having missing data at week 48.

Adverse events were similar in each group with no serious grade 3/4 events linked to study drugs. The only lab abnormality reported as serious was an elevated ALT related to hepatitis B.

The lower dose of islatravir in this study didn’t lead to any significant differences between arms in mean change from baseline in CD4 (p=0.88) or lymphocyte counts (p=0.23) at week 48, or in any discontinuations. There were also no between group differences in changes in weight or BMI between baseline and week 48.

At week 48, all participants were given the option to switch to ISL+LEN with extended follow-up visits every 3 months.

These results supported further development in two randomised, placebo-controlled Phase 3 switch studies using a similar design but with coformulated ISL/LEN that are currently recruiting participants, but currently only in US sites. [4, 5]

3. Colson A et al. Efficacy and safety of weekly islatravir plus lenacapavir in PWH at 24 weeks: a phase ii study. CROI 2024, Denver. Oral abstract 208.
https://www.croiconference.org/abstract/efficacy-and-safety-of-weekly-islatravir-plus-lenacapavir-in-pwh-at-24-weeks-a-phase-ii-study (abstract)
https://watch.croiwebcasts.org/croi2024/ap/52354 (webcast)

ClinicalTrials.gov. Study to Compare an Oral Weekly Islatravir/Lenacapavir Regimen With Bictegravir/Emtricitabine/Tenofovir Alafenamide in Virologically Suppressed People With HIV-1 (ISLEND-1).

https://clinicaltrials.gov/study/NCT06630286

ClinicalTrials.gov. Study to Compare an Oral Weekly Islatravir/Lenacapavir Regimen With Standard of Care in Virologically Suppressed People With HIV-1 (ISLEND-2).

https://clinicaltrials.gov/study/NCT06630299

Once-weekly oral ART: islatravir plus lenacapavir 48 week results in phase 2 switch study

2. HTB. CROI 2024: Pipeline ART – new drugs and formulations. (19 March 2024).

https://i-base.info/htb/47354