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LONG-TERM SAFETY AND EFFICACY OF CAB AND RPV AS 2-DRUG ORAL MAINTENANCE THERAPY
David A. Margolis1, Cynthia Brinson2, Graham H. Smith3, Joseph J. Eron4, Gary J. Richmond5, Roger P. LeBlanc6, Peter E. Williams7, William Spreen1, Kenneth Sutton8, Britt S. Stancil9
1ViiV Hlthcare, Rsr Triangle Park, NC, USA,2Central Texas Clinical Rsr, Austin, TX, USA,3Maple Leaf Med Clinic, Toronto, Ontario, Canada,4Univ of North Carolina at Chapel Hill, Chapel Hill, NC, USA,5Gary J Richmond MD PA, Ft Lauderdale, FL, USA,6Clinique OPUS, Montréal, Québec, Canada,7Janssen Rsr and Development, Beerse, Belgium,8ViiV Hlthcare, Raleigh, NC, USA,9PAREXEL Intl, Durham, NC, USA
Cabotegravir (CAB), an HIV INSTI is under development in both oral and long-acting (LA) injectable formulations. LATTE was designed to select a daily oral dose of CAB and to evaluate a two drug ART regimen with rilpivirine (RPV), as suppressive maintenance therapy. Results enabled the LATTE-2 study to evaluate CAB LA + RPV LA dosed once every 1 or 2 months.
Phase 2b, multicentre, partially-blinded dose-ranging study in ART-naïve HIV infected adults, randomized 1:1:1:1 to the induction regimen of once daily oral CAB 10, 30, or 60 mg or efavirenz (EFV) 600 mg with TDF/FTC or ABC/3TC through W24. CAB patients (Pts) with VL <50 c/mL immediately prior to W24 discontinued NRTIs and began RPV 25 mg as a two drug oral maintenance regimen through W96. No change was made to the EFV arm. After W96, at the start of the open-label (OL) phase, all Pts randomized to CAB were given the option to continue on the sponsor selected dose (30 mg) of CAB. EFV arm Pts completed the study at W96. The OL phase is ongoing and CAB Pts have completed W144, 120 weeks on a two-drug ART regimen as of this analysis.
243 Pts were randomized and initiated treatment (ITT-E). Of those randomized to CAB (n=181), 160 Pts began the maintenance regimen (W24) and138 continued into OL phase (W96). Amongst Pts who began CAB + RPV at W24, 76% maintained <50 c/mL, and 8% were virologic non-responders by Snapshot at W144 (ITT-ME). There were 9 protocol defined virologic failures (PDVF) on CAB, 3 occurred after W96. One Pt developed treatment emergent (TE) NNRTI resistance mutations at W132. No Pts developed TE major INI resistance mutations since W96. In total, 5 Pts developed TE resistance to one or both agents during the study. During the maintenance and OL phases, 7 (4%) reported drug-related AEs ≥ Grade 2. SAEs occurred in 15 (9%) CAB Pts (none drug related) and 4 (3%) withdrew due to AEs. Maintenance TE maximum lab abnormalities ≥ Grade 3 occurred in 25% of CAB Pts, with lipase and creatine kinase only having ≥5% of Pts (5% and 9% respectively). 17% of CAB Pts had a maintenance TE graded ALT, <1% were ≥ Grade 3.
As maintenance therapy in virologically suppressed Pts, the two drug regimen CAB + RPV provided durable viral suppression through W144. CAB + RPV continues to be generally safe and well tolerated; these data support progression to phase 3 studies.