ViiV Healthcare, a global specialist HIV company with GSK, Pfizer Inc. and Shionogi Limited as shareholders, announced that the phase IIb study LATTE 2 (NCT02120352) met its primary endpoint at 32 weeks. These results show that the investigational, long acting, injectable formulations of cabotegravir (ViiV Healthcare) and rilpivirine (Janssen) were comparable in maintaining viral suppression rates to a three drug oral regimen of investigational cabotegravir and two nucleoside reverse transcriptase inhibitors (NRTIs). The 32-week results of LATTE 2 will be presented at a forthcoming scientific conference. ViiV Healthcare and Janssen Sciences Ireland UC (Janssen) are collaborating to conduct LATTE 2.
Viral suppression rates (plasma HIV-1 RNA <50 c/ml by FDA snapshot analysis) for patients at 32 weeks receiving two drug maintenance therapy with investigational long acting cabotegravir (CAB LA) and long acting rilpivirine (RPV LA) dosed every 8 weeks (Q8W, 95 per cent) or every 4 weeks (Q4W, 94 per cent) were comparable to the rate observed in patients continuing with a three drug oral regimen of investigational CAB + NRTIs (91 per cent).
Patients switching to CAB LA and RPV LA administered Q4W reported more adverse events (AEs) leading to withdrawal (5 per cent; n=6) compared with those receiving an injection Q8W (2 per cent; n=2) or who continued on oral CAB + NRTIs (2 per cent, n=1). The most common adverse event (AE) reported by patients was injection site pain (93 per cent of injection recipients). Two patients in the Q8W arm (none in the Q4W arm) withdrew for injection intolerance. Two patients met protocol defined virologic failure criteria, Q8W (n=1), oral (n=1); neither patient had evidence of resistance at failure.
“ViiV Healthcare is committed to identifying new therapeutic options for physicians and people living with HIV. These initial phase IIb data investigating long-acting cabotegravir and rilpivirine are promising and build on the results we have seen to date. We look forward to seeing further results as we move into phase III,” said John C Pottage, Jr, MD, chief scientific and medical officer, ViiV Healthcare.
Following the results of the proof of concept two-drug oral dose-ranging study LATTE1, LATTE 2 was initiated as a phase IIb, multicentre, open label 96-week study investigating CAB LA with RPV LA as a two-drug antiretroviral (ART) regimen for suppressive maintenance therapy in ART-naïve, HIV infected adults. LATTE 2 included adults (n=309) who, after reaching virologic suppression on oral therapy with once-daily investigational oral cabotegravir 30mg + 2 NRTIs (n=286, 93 per cent), were subsequently randomised to one of three study arms to receive either CAB LA + RPV LA injections every 4 weeks (n=115, Q4W), 8 weeks (n=115 Q8W) or continued on oral CAB + NRTIs (n=56).
Cabotegravir is an investigational integrase strand transfer inhibitor (INSTI) and analogue of dolutegravir (Tivicay). Cabotegravir is being developed by ViiV Healthcare for the treatment and prevention of HIV and is currently being evaluated as a once-daily oral tablet formulation and as a LA nanosuspension formulation for intramuscular (IM) injection.
Rilpivirine is a once daily non-nucleoside reverse transcriptase inhibitor (NNRTI) used for the treatment of human immunodeficiency virus (HIV-1) infection in combination with other antiretroviral agents in antiretroviral treatment-naïve adult patients with a viral load = 100,000 HIV RNA copies/ml.
Rilpivirine was developed by Janssen. Rilpivirine is approved in US and EU as Edurant as a single agent tablet dosed at 25mg taken once a day. The overall safety profile of rilpivirine is based on phase III clinical studies. Rilpivirine is also available in the United States (US) and the European Union as part of a once daily fixed dose antiretroviral combination with Gilead Sciences Inc’s tenofovir and emtricitabine. This combination, known as Complera (US) or Eviplera.
Rilpivirine is currently being developed as a long-acting nanosuspension formulation for intramuscular (IM) injection.