Presentation Transcript

1. Dolutegravir (DTG) is Superior to Raltegravir (RAL) in ART-Experienced, Integrase-Naive Subjects: Week 48 Results From SAILING (ING111762)

   Pedro Cahn,1 Anton Pozniak,2 Horacio Mingrone,3 Carlos Brites,4 Jaime FedericoAndrade-Villanueva,5 Jan Fourie,6 Moti Ramgopal,7 Debbie Hagins,8 Jose Madruga,9Tamara Newman,10 John Lombaard,11 David Dorey,12 Mark Underwood,13 Sandy Griffith,13 Sherene Min,13 on behalf of the extended SAILING study team 1Fundación Huésped, Buenos Aires, Argentina; 2Chelsea and Westminster Hospital NHS Foundation Trust, London, UK; 3Fundación IDEAA, Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina; 4Complexo Hospitalar Prof. Edgard Santos, Universidade Federal da Bahia, Salvador, Brazil; 5Hospital Civil de Guadalajara “Fray Antonio Alcalde,” CUCS, Universidad de Guadalajara, Guadalajara, Mexico; 6Fourie Medical Centre, Dundee, South Africa; 7Midway Immunology and Research Center, Fort Pierce, FL, USA; 8Chatham CARE Center, Savannah, GA, USA; 9Centro de Referencia e Treinamento DST/AIDS, São Paulo, Brazil; 10Instituto de Infectologia Emílio Ribas, São Paulo, Brazil; 11JOSHA Research, Bloemfontein, South Africa; 12-13GlaxoSmithKline, 12Mississauga, ON, Canada; 13Research Triangle Park, NC, USA
2. Study Rationale Dolutegravir has been shown to be effective in antiretroviral (ART)-naive (SPRING-2 and SINGLE) and integrase inhibitor (INI)-resistant subjects (VIKING-3). SAILING was designed to test the efficacy and safety of DTG versus RAL when used with a background regimen of 2 antiretrovirals (1 of which must have been fully active) in ART-experienced, INI-naive subjects with at least 2-class drug resistance.
3. SAILING (ING111762) Study Design DTG 50 mg QD + RAL PBO + BR HIV ART-experienced, INI-naive HIV-1 RNA >400 c/mLa 1:1 Randomization stratified by HIV-1 RNA (≤ or >50,000), DRV/r use and # of fully active drugs RAL 400 mg BID + DTG PBO + BR Week 24 Randomization Week 48primary analysis planned interim a At Screening and a second consecutive test >400 c/mL within 4 months prior to Screening (if Screening HIV-1 RNA >1000 c/mL, no additional HIV-1 RNA assessment was needed). PBO, placebo; BR, background regimen comprising at least 1 and no more than 2 active agents.
4. Baseline Characteristics
5. Subject Accountability Patients screenedN=1441 Not randomizedN=717 Randomized phase Patients randomizedN=724 Patients randomizedto DTG 50 mg QDN=360 Patients randomizedto RAL 400 mg BIDN=364 Not treatedN=3 Treated (ITT-E)N=357 Treated (ITT-E)N=362 Not treatedN=2 Patients excluded at site 083523N=3 mITT-EN=354 mITT-EN=361 Patients excluded at site 083523N=1 Completion status at Week 48 299 (84%) completed 55 (16%) withdrew 4 adverse event 20 lack of efficacy 9 protocol deviation 5 stopping criteria 5 lost to follow-up 1 investigator discretion 11 withdrew consent Completion status at Week 48 283 (78%) completed 78 (22%) withdrew 11 adverse event 42 lack of efficacy 6 protocol deviation 3 stopping criteria 10 lost to follow-up 1 investigator discretion 5 withdrew consent
6. Proportion (95% CI) With HIV-1 RNA <50 c/mL (Snapshot, mITT-E) DTG 50 mg QD was statistically superior to RAL 400 mg BID at Week 48. 100 90 80 71% 70 64% 60 Proportion (%) 50 40 *Adjusted treatment difference (95% CI): 7.4% (0.7%, 14.2%); P=0.03 30 20 10 0 BL 4 8 12 16 24 32 40 48 Week Mean CD4+ change from Baseline was similar between arms: DTG: +162.4 cells/mm3 (n=294); RAL: +153.2 cells/mm3 (n=283). *Adjusted difference based on stratified analysis adjusting for Baseline HIV-1 RNA (≤50,000 c/mL vs >50,000 c/mL), DRV/r use without primary PI mutations and Baseline PSS (2 vs <2).
7. Primary Endpoint: HIV-1 RNA <50 c/mL at Week 48 95% CI for difference FavorsRAL FavorsDTG 0.7 7.4 14.2 -20% -12% 0 20%
8. Percentage of Subjects With HIV-1 RNA <50 c/mL by Subgroup Difference (DTG-RAL) and 95% CI Subgroup Response rates In favor of RAL In favor of DTG -30 -20 -10 0 10 20 30
9. Sensitivity Analyses
10. Protocol-Defined Virologic Failure Non-response HIV-1 RNA <1 log10 c/mL decrease by Week 16, unless <400 c/mL HIV-1 RNA ≥400 c/mL on or after Week 24, through Week 48 Rebound HIV-1 RNA ≥400 c/mL after confirmed <400 c/mL HIV-1 RNA >1 log10 c/mL above nadir (lowest prior value ≥400 c/mL)
11. Protocol-Defined Virologic Failure Fewer PDVFs for DTG versus RAL by Week 48
12. Treatment-Emergent Resistance to INI and to Background Regimen Key Secondary Endpoint Supportive Analysis Treatment-emergent resistance to background regimen was also statistically significant.** DTG 1% vs RAL 3%, adjusted difference (95% CI) of -2.2% (-4.3%, -0.1%) *DTG was superior vs RAL at Week 48 (P=0.003), pre-specified and adjusted for multiple testing. **This analysis was pre-specified but was unadjusted for multiple testing.
13. Adverse Events
14. Select Laboratory Abnormalities
15. Conclusions DTG once daily has higher virologic efficacy when compared with RAL twice daily in a treatment-experienced, INI-naive population. 71% on DTG versus 64% on RAL had HIV-1 RNA <50 c/mL at Week 48. DTG 50 mg once daily had a similar tolerability and safety profile to RAL twice daily with a wide variety of background regimens in treatment-experienced subjects. DTG statistical superiority was driven by fewer withdrawals due to lack of efficacy, lower number of protocol defined virologic failures and lower treatment emergent resistance.
16. Acknowledgments We thank everyone who has contributed to the success of this study, including All study participants and their families The SAILING clinical investigators and their staff The GSK and ViiV Healthcare study team This study was funded by ViiV Healthcare