CL Vavro, 1 J Huang, 2 C Avatapally, 1 S Min, 1 and M Ait-Khaled 3. GlaxoSmithKline: 1 Research Triangle Park,NC, USA; 2 Toronto, ON, Canada; 3

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1 Durable Efficacy and Limited Integrase Resistance Evolution in Subjects Receiving Dolutegravir After Failing Prior Integrase Inhibitor (INI) Regimens: Week 48 Results from VIKING-3 CL Vavro, 1 J Huang, 2 C Avatapally, 1 S Min, 1 and M Ait-Khaled 3 GlaxoSmithKline: 1 Research Triangle Park,NC, USA; 2 Toronto, ON, Canada; 3 Stockley Park, London, UK

2 Study Design HIV-1 RNA 500 copies/ml *Resistance to RAL and/or EVG *Resistance to 2 ART classes other than INIs Screening period up to a maximum of 42 days Functional monotherapy phase DTG 50 mg BID and continue failing regimen Optimised phase DTG 50 mg BID + optimised background regimen with OSS 1 Screening visit ~Day -35 *Screening or documented historical evidence. Day 1 Day 8 Week 24 analysis *OSS (overall susceptibility score) determined by Monogram Biosciences Week 48 analysis Endpoints Day 8: Change from BL in HIV-1 RNA with DTG 50 mg BID functional monotherapy Week 24: Proportion with <50 copies/ml with DTG 50 mg BID plus optimised background This presentation examines efficacy and resistance at Week 48 Castagna et al. JID

3 Baseline Characteristics (ITT-E, N=183) Advanced disease and ARV treatment history at baseline Extensive ARV resistance across all drug classes DTG 50 mg BID* (N=176) Q Q148+1 N155H Y143 2 Primary No Primary Detected Subjects N (%) 21 (11) 31 (17) 30 (18) 28 (15) 7 (4) 59 (32) Median DTG FC Q Q Min Max *By Baseline IN mutation category 7 subjects with no DTG FC data Castagna et al. JID

4 Day 8, Week 24, and Week 48 Efficacy Results (ITT-E, N=183) Percentage of subjects with HIV-1 RNA <50 copies/ml Day 8 change from BL: log 10 copies/ml, P<0.001 Good response at Week 24 (69%) by Snapshot (MSDF) despite extensive resistance 135/183 (74%) <400c/mL Response maintained at Week 48 (63%) by Snapshot (MSDF) 125/183 (68%) <400 c/ml Castagna et al. JID /183 (69%) 116/183 (63%) 0 BL D8 W4 W8 W12 W16 W24 W32 W40 W48 Time

5 Week 24 and Week 48 Response by Baseline IN Mutations (ITT-E, Snapshot algorithm) % With <50 c/ml HIV-1 RNA at Week 24 % With <50 c/ml HIV-1 RNA at Week 48 Derived IN Mutation Group at BL N Total % 63% No Q % 71% Q secondary mutation* 36 58% 56% Q secondary mutations* 21 24% 29% *Key secondary mutations were G140A/C/S, L74I and E138A/K/T Antiviral response was sustained through Week 48 Difference in response rates between Week 24 and Week 48 was primarily for non-virological reasons. Castagna et al. JID. 2014

6 Week Safety No new safety signals since Week 24 analysis Most common drug related AEs were nausea (6%) and diarrhea (5%) Few AEs leading to withdrawal, n=8 (4%) No new drug related SAE s since Week 24. Lab abnormalities: Through Week 48, Grade 3 or 4 ALT elevations in 7 subjects (4%) Median changes in creatinine noted by Week 4, stable to Week 48 Castagna et al. JID. 2014

7 Number (%) of Subjects who Met Protocol Defined Virologic Failure (PDVF) DTG 50 mg BID ITT-E, N=183 Cumulative Number of PDVF * PDVF At Week 24 PDVF At Week 48 All PDVF 36 (20%) 41 (22%) Virologic non-response 21 (11%) 21 (11%) Rebound 15 (8%) 20 (11%) *PDVF was defined as any HIV-1 RNA value >400 c/ml and meeting following criteria: <0.5 log 10 decrease at Day 8, confirmed decrease of < 1 log 10 c/ml by Week 16, confirmed 400 c/ml on or after Week 24, confirmed 400 c/ml after prior confirmed <400 c/ml or confirmed >1 log 10 c/ml above a nadir of 400 c/ml 5 (2%) subjects experienced PDVF between Week 24 and Week 48. Four additional subjects met PDVF post Week 48 at Week 60 (N=2), 72 and 84. A total of 45 subjects were evaluated for treatmentemergent resistance.

8 Distribution of Baseline IN Mutation Category ITT-E (N=183) Subjects with PDVF (N=45) IN Mutation Category Baseline PDVF Q (11%) 13 (29%) Q (17%) 9 (20%) 2 Primary mutations 8 (4%)* 2 (4%)** Y (15%) 4 (9%) N (18%) 4 (9%) T66 1 (<1) - Primary Not Detected 60 (33%) 13 (29%)*** * 4 subjects with Q148 with T66 or Y143 mutations ** 2 subjects with Q148 with Y143 or T66 mutations ***6 subjects with only screening or historic evidence of Q148 mutations but not present at baseline 67% (30/45) who met PDVF had Q148 mutations at baseline or historically

9 Emergent IN Resistance Detected at the Time of PDVF Codon in Integrase DTG 50mg BID (PDVF Genotypic Pop) (n=39)* Genotype at PDVF ANY 22 (56%) 97 T97T/A, T97A 10 (26%) 138 E138A, E138E/K, E138K 9 (23%) 148 Q148H, Q148Q/H, Q148Q/R/K 6 (15%)** 140 G140G/S, G140S 4 (10%) 155 N155H 4 (10%) 74 L74L/M/V, L74L/M, L74I 3 (8%) 92 E92E/Q 2 (5%) 157 E157E/Q 1 (3%) 147 S147G 1 (3%) 143 Y143Y/H 1 (3%) *Only 39/45 subjects with paired baseline and PDVF samples ** 3 subjects with historic Q148H; 2 with Q148H at screen but not Baseline; one with Q148R at Baseline and Q148Q/R/K at PDVF Emergent mutations were at well characterized IN resistance-associated mutations 18/22 (82%) subjects harbor Q148 pathway virus at Baseline or historic

10 Emergent IN Resistance Detected at the Time of PDVF DTG Fold change ratio PDVF/Baseline DTG 50 mg BID (PDVF Phenotypic pop) n 39 <1 6 (15%) 1-<2 15 (38%) 2-<4 4 (10%) 4-<8 4 (10%) 8 10 (26%) 18 subjects, with >2 DTG fold change ratio, had treatment-emergent genotypic resistance No single mutation conferred high DTG FC

11 Emergent mutations in 18 Subjects with Q148 Virus Pathway at Baseline or Historic* (emergent mutations shown in bold) Q N=7 Q148H + G140S Q148H + G140S+ T97T/A (n=3) Q148H + G140S+ E138K Q148H + G140S+ E138K +E92E/Q Q148H + G140S+ E138E/A +T97A Q148H + G140S+ E138K +T97A Q N=6 Q148H+G140S+E138T/K/A Q148H+G140S+E157Q Q148H+G140S+E138T/A+ G193E DTG Treatment Q148H + G140S+ E138T/K/A +E157E/Q Q148H + G140S+ E138T +T97A Q148H + G140S+ E138T +N155H Q148H + G140S +E157Q +N155H Q148Q/R/K + G140A +E138A + G193E Q148Q/H + G140G/S+ E138T/A +G193E+ L74L/M+T97T/A Historic* Q148 N=5 Q148H Q148H + G140G/S+ E138E/K + T97T/A+E92E/Q Q148H + G140S+ E138A + T97T/A Q148H + G140S+ E138A + T97T/A Q148Q/H + G140S+ E138E/K Q148Q/H + G140S+N155H *Historic includes subjects with screening Q148 but not at baseline

12 Conclusions for Efficacy and Resistance DTG 50 mg BID showed a good and durable efficacy in INI resistant patients 69% and 63% with HIV-1 RNA <50 copies/ml at Week 24 and Week 48 Week 24 responses maintained through Week 48 in Q and Q virus Safety profile on DTG 50mg BID similar to that with DTG 50 mg once daily For individuals with Protocol-defined Virologic Failure Few new cases of PDVF from Week 24 to Week 48 Limited IN resistance evolution with only previously identified INI-associated mutations detected Majority with treatment-emergent resistance harboured Q148 mutations at baseline or historic.

13 Acknowledgements With thanks to all who participated in and supported VIKING-3: All subjects and their families VIKING-3 investigators and site staff Contributors from GSK, and ViiV Healthcare This study was sponsored by ViiV Healthcare