Prescribing Information can be found at the end of the presentation

Transcription

1 Switching to Dolutegravir /Abacavir/Lamivudine Fixed Dose Combination ( FDC) from a PI, INI or NNRTI Based Regimen Maintains HIV Suppression at 48 Weeks Prescribing Information can be found at the end of the presentation 1

2 Introduction (Triumeq) is a complete regimen built around DTG, an unboosted INSTI with a high barrier to resistance First approval of : August 2014 in North America The study enrolled April 2014 to Oct 2014 STRIIVING was conducted to evaluate the efficacy, safety, tolerability, and treatment satisfaction of switching to in subjects stable and suppressed on a variety of regimens

3 STRIIVING Study Design Countries: US, Canada, Puerto Rico Open-label, randomized 2 NRTIs + 1:1 PI/r Current ART a Screening 0 Week 24 Week 48 Inclusion criteria Virologically suppressed (confirmed HIV-1 RNA <50 c/ml) HLA-B*5701 negative a Stable suppressive current ART with 2 NRTIs plus either a PI, an NNRTI, or an INI. 40% PIs, at least 25% INIs. Primary endpoint at 24 weeks: VL <50 c/ml (Snapshot) 90% power based on 10% non-inferiority margin (estimated response rate = 85%). Assessments CD4 cell count changes Clinical and laboratory safety Lipids, renal, bone, and cardiovascular changes Development of resistance Treatment satisfaction

4 Study Populations Subjects randomized to on Day 1 who received at least 1 dose of Early-switch Subjects randomized to continue current ART on Day 1, completed Early Switch Phase at W24, and received at least 1 dose of upon switching at Week 24 Late-switch Treatment arm Data included Early-switch Early-switch Day 1 to Week 24 Day 1 to Week 48 Late-switch Week 24 to Week 48

5 Study Disposition: Week 48 Randomized and treated (n=275) Completed Wk 24 (N=239, 87%) Completed Wk 48 (N=230, 84%) Screened (N=841) Randomized and treated cart (n=278) Completed Wk 24 (N=245, 88%) Late switch to (N=244) Completed Wk 48 (N=230, 94%) Early Switch group Discontinuations: Day 1- Week 24 Day 1- Week 48 Adverse event 10 (4%) 10 (4%) Lack of efficacy (virologic failure) 0 0 Protocol deviation 15 (5%) 15 (5%) Stopping criteria met 0 0 Lost to follow-up 3 (1%) 8 (3%) Investigator discretion 3 (1%) 5 (2%) Withdrew consent 4 (1%) 6(2%) Per sponsor request 1 (<1%) 0 Late Switch group Discontinuations: Week Adverse event 4 (2%) Lack of efficacy (virologic failure) Protocol deviation 1 (<1%) Stopping criteria met 1 (<1%) Lost to follow-up 3 (1%) Investigator discretion 0 Withdrew consent 5 (2%) 0

6 STRIIVING 48 Week Early Switch Arm Week 24 HIV-1 RNA <50 copies/ml, % a ITT-E analysis Virologic success 92 1, Day 1 Week 24 (n=275) a cart, Day 1 Week 24 (n=278) a, Day 1 Week 48 (n=275) b Switch to, Week 24 Week 48 (n=244) b 1 <1 <1 Virologic non-response No virologic data 7

7 STRIIVING 48 Week Early Switch Arm Week 24 and 48 HIV-1 RNA <50 copies/ml, % a ITT-E analysis Virologic success 92 1, Day 1 Week 24 (n=275) a cart, Day 1 Week 24 (n=278) a, Day 1 Week 48 (n=275) Switch to, Week 24 Week 48 (n=244) b 1 <1 <1 Virologic non-response No virologic data 7

8 STRIIVING 48 Week Late Switch Arm 24 Weeks Post Switch Switch to, Week 24 Week 48 (n=244) HIV-1 RNA <50 copies/ml, % Virologic success <1 Virologic non-response 7 No virologic data

9 Week 24 and 48 Snapshot Outcomes Early Switch Day 1 to Wk 24 Virologic Success 233 (85) Virologic Non-response 3 (1) Data in window not below threshold 3 (1) Discontinued while VL not <50* 0 No Virologic Data 39 (14) Discontinued due to AE or death 10 (4) Discontinued for other reasons a 25 (9) Missing data during window but 4 (1) on study 4% of the Early Switch group discontinued treatment due to AEs at Week 24, with none between Weeks 24 and 48; 2% of the Late Switch group discontinued treatment due to AEs between Weeks 24 and 48 *Includes categories: Discontinued for lack of efficacy and Discontinued for other reason while not below threshold

10 Week 24 and 48 Snapshot Outcomes Day 1 to Wk 24 Early Switch Day 1 to Wk 48 Virologic Success 233 (85) 227 (83) Virologic Non-response 3 (1) 1 (<1) Data in window not below threshold 3 (1) 1 (<1) Discontinued while VL not <50* 0 0 No Virologic Data 39 (14) 47 (17) Discontinued due to AE or death 10 (4) 10 (4) Discontinued for other reasons a 25 (9) 32 (12) Missing data during window but on study 4 (1) 5 (2) 4% of the Early Switch group discontinued treatment due to AEs at Week 24, with none between Weeks 24 and 48; 2% of the Late Switch group discontinued treatment due to AEs between Weeks 24 and 48 *Includes categories: Discontinued for lack of efficacy and Discontinued for other reason while not below threshold

11 Week 24 and 48 Snapshot Outcomes Early Switch Late Switch Day 1 to Wk 24 Day 1 to Wk 48 N=244 Wk 24 to Wk 48 Virologic Success 233 (85) 227 (83) 224 (92) Virologic Non-response 3 (1) 1 (<1) 3 (<1) Data in window not below threshold 3 (1) 1 (<1) 3 (<1) Discontinued while VL not <50* No Virologic Data 39 (14) 47 (17) 17 (7) Discontinued due to AE or death 10 (4) 10 (4) 4 (2) Discontinued for other reasons 25 (9) 32 (12) 7 (3) Missing data during window but on study 4 (1) 5 (2) 6 (2) 4% of the Early Switch group discontinued treatment due to AEs at Week 24, with none between Weeks 24 and 48; 2% of the Late Switch group discontinued treatment due to AEs between Weeks 24 and 48 *Includes categories: Discontinued for lack of efficacy and Discontinued for other reason while not below threshold

12 Virologic Endpoints: No subjects met protocol-defined virologic failure in either study arm Early Switch Late Switch Day 1 to Wk 24 Day 1 to Wk 48 N=244 Wk 24 to Wk 48 PDVF a Viral load 50 c/ml (snapshot) 3 (1%) 1 (<1) 3 (1%) 4 subjects >50 at Week 48 window: ES (51), LS (54, 53, 156); All 4 resuppressed < 50 c/ml a Subjects with HIV-1 RNA 400 c/ml on 2 consecutive assessments any time after randomization are withdrawn = meets protocol defined virologic failure.

13 Adverse Events: Overall Summary Early Switch Day 1 to Wk 24 Any adverse event, 180 (65) Any drug-related event 57 (21) (occurring 2% of subjects in either arm) Nausea 20 (7) Diarrhea 9 (3) Fatigue 9 (3) Headache 7 (3) Insomnia 5 (2) Dizziness 5 (2) Abnormal dreams 5 (2) Any serious event a 6 (2) Any fatal event a 1 (<1) Discontinuations due to AE or death 10 (4) a None were considered drug-related events.

14 Adverse Events: Overall Summary Day 1 to Wk 24 Early Switch Day 1 to Wk 48 Any adverse event, 180 (65) 206 (75) Any drug-related event 57 (21) 60 (22) (occurring 2% of subjects in either arm) Nausea 20 (7) 20 (7) Diarrhea 9 (3) 9 (3) Fatigue 9 (3) 9 (3) Headache 7 (3) 7 (3) Insomnia 5 (2) 5 (2) Dizziness 5 (2) 5 (2) Abnormal dreams 5 (2) 4 (1) Any serious event a 6 (2) 9 (3) Any fatal event a 1 (<1) 1 (<1) Discontinuations due to AE or death 10 (4) 10 (4) a None were considered drug-related events.

15 Adverse Events: Overall Summary Day 1 to Wk 24 Early Switch Day 1 to Wk 48 Late Switch N=244 Wk 24 to Wk 48 Any adverse event, 180 (65) 206 (75) 146 (60) Any drug-related event 57 (21) 60 (22) 32 (13) (occurring 2% of subjects in either arm) Nausea 20 (7) 20 (7) 9 (4) Diarrhea 9 (3) 9 (3) 3 (1) Fatigue 9 (3) 9 (3) 3 (1) Headache 7 (3) 7 (3) 6 (2) Insomnia 5 (2) 5 (2) 6 (2) Dizziness 5 (2) 5 (2) 2 (<1) Abnormal dreams 5 (2) 4 (1) 3 (1) Any serious event a 6 (2) 9 (3) 6 (2) Any fatal event a 1 (<1) 1 (<1) 1 (<1) Discontinuations due to AE or death 10 (4) 10 (4) 4 (2) a None were considered drug-related events.

16 Common Adverse Events: ( 5% in Any Treatment) Early Switch Day 1 to Wk 24 Nausea 27 (10) Upper respiratory tract infection 20 (7) Diarrhea 20 (7) Fatigue 19 (7) Headache 13 (5) Cough 14 (5) Insomnia 10 (4) Nasopharyngitis 10 (4)

17 Common Adverse Events: ( 5% in Any Treatment) Early Switch Day 1 to Wk 24 Day 1 to Wk 48 Nausea 27 (10) 28 (10) Upper respiratory tract infection 20 (7) 35 (13) Diarrhea 20 (7) 20 (7) Fatigue 19 (7) 22 (8) Headache 13 (5) 17 (6) Cough 14 (5) 17 (6) Insomnia 10 (4) 14 (5) Nasopharyngitis 10 (4) 13 (5)

18 Common Adverse Events: ( 5% in Any Treatment) Early Switch Late Switch Day 1 to Wk 24 Day 1 to Wk 48 N=244 Wk 24 to Wk 48 Nausea 27 (10) 28 (10) 15 (6) Upper respiratory tract infection 20 (7) 35 (13) 22 (9) Diarrhea 20 (7) 20 (7) 9 (4) Fatigue 19 (7) 22 (8) 6 (2) Headache 13 (5) 17 (6) 10 (4) Cough 14 (5) 17 (6) 6 (2) Insomnia 10 (4) 14 (5) 9 (4) Nasopharyngitis 10 (4) 13 (5) 6 (2)

19 Conclusions Efficacy The virologic response rate was maintained through 48 weeks in the Early Switch group In the Late Switch group, virologic suppression was observed in 92% of subjects on (24 weeks post-switch) There were no PDVFs in the study Tolerability There were no further discontinuations due to AEs in the Early Switch arm post-week 24 Low rates of discontinuations in the Late Switch arm (2%) Summary Data through 48 weeks support switching to once daily for HIV-1 subjects on stable suppressive cart

20 Acknowledgments We thank everyone who has contributed to the success of this study, including All study participants and their families The GlaxoSmithKline and ViiV Healthcare study teams PPD The clinical investigators and their staff Canada United States Baril LeBlanc Baxter Dretler Hite Martorell Rashbaum Shikuma Hoffman- Conway Logue Benson Dube Terry McDonald Rhame Shon de Wet Loutfy Bhatti Edelstein Hsiao Meier Richmond Simon Fraser Rachlis Blick Evans/Martin Huhn Mills Riddell Sloan Kasper Trottier Bolan Feinberg Jain Mounzer Ruane Small/Khoury Walmsley Bredeek Felizarta Jayaweera Nahass Salazar/ Rodriguez Stefanic Brennan Fife L. Johnson Newman Scarsella Van Dam Puerto Rico Brinson Flamm M. Johnson Nguyen Schneider Vanig Marquez Calvo Gallant Kinder Novak Schrader Wade Chang/P. Melendez- Rivera Johnson Garcia-Diaz Klein Osiyemi Scott Ward Santiago Colon Cunningham Grossberg Kumar Parks Scribner Wheeler Zorrilla Cutro Hagins Lake Pierone Sha DeJesus Hare Lalezari Prelutsky Shalit Dietz Henry Lewis Ramgopal Shamblaw

21 Prescribing Information Triumeq dolutegravir 50mg/abacavir 600mg/lamivudine 300mg tablets See Summary of Product Characteristics before prescribing. Indication: HIV in over 12 years and > 40kg. Screen for HLA-B*5701 prior to use. Do not use if HLA-B*5701 positive. Dose: one tablet once daily with or without food. Elderly: Limited data in 65+ yrs. Creatinine clearance <50ml/min or moderate/severe hepatic impairment: Not recommended. Monitor closely in mild hepatic impairment. Contraindications: Hypersensitivity to any ingredient. Co-administration with dofetilide. Warnings/precautions: Both abacavir and dolutegravir are associated with risk of hypersensitivity reactions (HSR). Do not initiate in HLA-B*5701+ or previous suspected abacavir HSR. Stop Triumeq without delay if HSR suspected. Never reintroduce any dolutegravir- or abacavir-containing product after suspected HSR. Risks of immune reactivation syndrome, osteonecrosis, increased weight, lipids, glucose. Monitor LFTs in Hepatitis B/C co-infection. Inconclusive data on relationship between abacavir and MI; minimise all modifiable CV risk factors (e.g. smoking, hypertension, hyperlipidaemia). Not recommended if dolutegravir required b.d. (with etravirine [without boosted PI], efavirenz, nevirapine, rifampicin, boosted tipranavir, carbamazepine, oxcarbazepine, phenytoin, phenobarbital and St John s Wort). Use with cladribine not recommended. Use with Mg/Alcontaining antacids, calcium, multivitamins or iron requires dosage separation. Caution with metformin: monitor renal function and consider metformin dose adjustment. Pregnancy/lactation: Not recommended. Avoid breast-feeding. Side effects: See SPC for details. Headache, insomnia, sleep/dream disorders, GI disturbance, fatigue, hypersensitivity, anorexia, depression, dizziness, somnolence, lethargy, malaise, cough, nasal symptoms, rash, pruritus, alopecia, arthralgia, myalgia, asthenia, fever, elevations of ALT, AST and CPK, blood dyscrasias, suicidal ideation or suicide attempt, rhabdomyolysis, lactic acidosis, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis. Basic NHS costs: 30 tablets: EU/1/14/940/001. MA holder: ViiV Healthcare UK Ltd, 980 Great West Road, Brentford, Middlesex TW8 9GS. Further information is available from Customer Contact Centre, GlaxoSmithKline UK Ltd, Stockley Park West, Uxbridge, Middlesex UB11 1BT. POM S1A Triumeq is a registered trademark of the ViiV Healthcare Group of Companies Date of approval: January 2017 Zinc code: UK/TRIM/0037/14(7) Adverse events should be reported. For the UK, reporting forms and information can be found at Adverse events should also be reported to GlaxoSmithKline on Adverse events should be reported. For Ireland, adverse events should be reported directly to the HPRA; Freepost, Pharmacovigilance Section, Health Products Regulatory Authority, Earlsfort Terrace, Dublin 2, Tel: , medsafety@hpra.ie. Adverse events should also be reported to GlaxoSmithKline on