Sunlenca Plus Two Antibodies Shows Promise for Twice-Yearly Treatment

[Jim Allen]

NCT04811040 & next planned phase 2: NCT05729568

Very small (white & male) group but still interesting initial results.

POZ.com article in full: https://www.poz.com/article/sunlenca-plus-broadly-neutralizing-antibodies-shows-promise-twiceyearly-hiv-treatment

In Brief:

Two studies showed that Sunlenca has the potential to be used as a component of a long-acting treatment regimen, but so far there are no other drugs that can be given at such a long interval, so it still must be taken with daily pills. The approved regimen with the longest duration, ViiV Healthcare’s Cabenuva (injectable cabotegravir and rilpivirine), is administered once monthly or every other month.

Combining Sunlenca with long-acting broadly neutralizing antibodies could be another path forward. However, they are prone to resistance as the virus mutates, so they likely will work best in combination regimens.

Eron and colleagues evaluated a regimen of Sunlenca plus two bnAbs administered every six months. This clinical trial (NCT04811040) enrolled people who were on antiretroviral therapy with an undetectable viral load for at least 18 months. The participants were tested to ensure that their HIV was sensitive to both antibodies. Among 124 people initially screened, 55 met the susceptibility criteria. Of these, 34 were not enrolled because of a temporary clinical hold on Sunlenca (due to a problem with the original glass vial) or for other reasons.

Of the remaining 21 people, all but three were men, a majority were white and one third were Latino. The median age was 44 years, and they had been diagnosed with HIV for a median of 8.2 years and on treatment for a median of 2.6 years. All had a current CD4 count above 500, with a median of approximately 900, and they had never fallen below 350.

The study was originally designed to run for 52 weeks, at which point participants would restart their prior antiretroviral regimen. However, when Sunlenca became unavailable due to the clinical hold, the study was halted at 26 weeks, after just one dose, Eron explained.

Sunlenca, teropavimab and zinlirvimab (using either dose) all remained well above therapeutic levels through 26 weeks. At that point, 90% of participants in both groups maintained an undetectable viral load. One person who received the higher dose of zinlirvimab decided he preferred pills and withdrew from the study. One person in the lower-dose group experienced viral rebound, resumed their baseline regimen and again achieved viral suppression. CD4 counts remained stable in both groups.

“This study demonstrates that a combination of the bNAbs teropavimab and zinlirvimab together with lenacapavir can sustain viral suppression for six months in selected people with HIV,” the investigators concluded.

Upcoming phase 2:
https://clinicaltrials.gov/ct2/show/NCT05729568

Related thread:

https://forums.poz.com/index.php?topic=75017.0: Lenacapavir capsid inhibitor (GS-6207) - CAPELLA trial & CALIBRATE trial