Cabotegravir is a promising new investigational integrase inhibitor, formulated as a pill or a long-acting injection. One of the early studies of its oral formulation -- the Phase 2b LATTE study -- began more than six years ago.
Now, the final analysis of the LATTE study finds that a combination of oral cabotegravir and rilpivirine offers durable viral suppression as maintenance therapy over six years, and continued to be generally safe and well-tolerated.
David Margolis, M.D., M.P.H., director of HIV drug development at ViiV Healthcare, presented these final LATTE findings at the annual IDWeek conference in Washington, D.C. in early October.
Overall, Margolis said, updated LATTE data support previously published findings that support oral cabotegravir's use as maintainance therapy in previously treatment-naive patients who are virally suppressed.
Because cabotegravir is formulated as both an oral pill and as a long-acting injectable, the LATTE study design included several phases. In the first phase, 243 treatment-naive patients were randomly assigned to either receive daily doses of oral cabotegravir or efavirenz. Each regimen was paired with either emtricitabine/tenofovir disoproxil fumarate (TDF/FTC, Truvada) or abacavir/lamivudine (ABC/3TC, Epzicom).
After about six months, patients in the cabotegravir arm with suppressed viral load (<50 copies/mL) discontinued their NRTI regimen, swapping it out for oral rilpivirine (RPV, Edurant). The efavirenz arm remained on their existing therapy.
At about the two-year mark, the study switched into an open-label phase. All the patients in the cabotegravir arm were allowed to continue on their regimen -- albeit at the selected dose of 30 mg. They continued on this therapy for another four years, at which point the LATTE study concluded, and successful cabotegravir/rilpivirine patients transitioned to the POLAR study, a phase 2b study of long-acting injectable cabotegravir and rilpivirine.
Among the 160 patients who started treatment with cabotegravir and rilpivirine at six months, about two-thirds maintained suppressed viral load, one in ten had a viral load of greater than 50 copies/mL, and a quarter were categorized as "no virologic data" at the six-year timepoint.
Eleven patients failed treatment, as defined by the protocol. Six developed treatment-emergent resistance to one or both agents during the study. Of those, four developed major integrase inhibitor resistance. The typical patient in the cabotegravir/rilpivirine arm saw an increased CD4 count of 393 cells/mm3 (-174–1,118).
Serious adverse events occurred in 9% of cabotegravir patients who entered the open-label and maintenance phase of the study, although none of those were drug-related. During the open-label phase, 3% withdrew due to adverse events.
As well, a large portion of patients -- just under half -- reported treatment-emergent laboratory abnormalities. In particular, 16% developed creatine kinase abnormalities and 10% developed lipase abnormalities. However, Margolis said these were "transient and resolved in spite of continued treatment."
ViiV requested Food and Drug Administration approval for injectable and oral cabotegravir + rilpivirine in April 2019. The drugs are being studied for HIV treatment and prevention.