ALLY-2  Design  Objective –SVR 12 (HCV RNA < 25 IU/ml), with 95% CI, in treatment-naïve genotype 1 treated for 12 weeks DCV + SOF 400 mg QD DCV + SOF.

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Presentation transcript:

ALLY-2  Design  Objective –SVR 12 (HCV RNA < 25 IU/ml), with 95% CI, in treatment-naïve genotype 1 treated for 12 weeks DCV + SOF 400 mg QD DCV + SOF 400 mg QD Randomisation* 2 : 1 Open-label ALLY-2 Study: DCV + SOF for HCV in HIV co-infection W8 N = 52 ≥ 18 years Chronic HCV infection Genotypes 1 to 6 Treatment-naïve or experienced, NS5A inhibitor-naïve HCV RNA ≥ 10,000 IU/ml Compensated cirrhosis** allowed HIV infection on ART** and HIV RNA < 50 c/ml and CD4 ≥ 100/mm 3, or no ART and CD4 ≥ 350/mm 3 Wyles DL. NEJM 2015, July 21, Epub ahead of print Treatment-experienced N = 101 Treatment naïve * Metavir F4 on biopsy, or Fibroscan > 14.6 kPa, or Fibrotest ® > APRI > 2 *** Permitted ARV : PI/r, NRTI, NNRTI, INSTI, MVC W12 DCV + SOF 400 mg QD N = 50 No randomisation Open-label –DCV QD : 60 mg, 30 mg with PI/r, 90 mg with NNRTI other than RPV * Randomisation was stratified on cirrhosis (yer or no) and genotype

Naïve 12W N = 101 Naïve 8W N = 50 Experienced 12W N = 52 Median age, years Female9%16%17% Genotype 1a 1b % 12% 11% 6% 1% 70% 12% 12% 6% 0 63% 21% 4% 8% 4% HCV RNA, log 10 IU/ml, median Cirrhosis9%10%29% HIV RNA < 50 c/ml94% 96% CD4/mm 3, median PI/r : DRV/r / ATV/r / LPV/r19% / 19% / 9%44% / 10% / 6%22% / 24% / 0 NNRTI : EFV / NVP / RPV18% / 5% / 5%17% / 2% / 2%16% / 6% / 2% Other : RAL / DTG / NRTI only22% / 3% / 017% / 2% / 020% / 8% / 4% Post-treatment W12 missing (LTFU)110 Baseline characteristics and patient disposition ALLY-2 ALLY-2 Study: DCV + SOF for HCV in HIV co-infection Wyles DL. NEJM 2015, July 21, Epub ahead of print

SVR 12 (HCV RNA < 25 IU/ml) Naïve 12W Naïve 8W Experienced 12W * All other genotypes : SVR 12 = 100% in naïve 12W and experienced 12W  SVR 12 : 100% with 12 weeks of DCV + SOF, with all NNRTI and PI/r, except DRV/r (95% in naïve 12W, 91% in experienced) ALLY-2 ALLY-2 Study: DCV + SOF for HCV in HIV co-infection % ( ) 76 (62-87) 98.1 ( ) Baseline HCV RNA log 10 IU/ml YesNo< 6 M All (N = 203)Genotype 1 (N = 168) ≥ 6 M Cirrhosis Genotype 1a* N Wyles DL. NEJM 2015, July 21, Epub ahead of print

SVR 12 (HCV RNA < 25 IU/ml) with 8 weeks of DCV + SOF ALLY-2 ALLY-2 Study: DCV + SOF for HCV in HIV co-infection % N Baseline HCV RNA log 10 IU/ml YesNo< 6 M AllGenotype 1 ≥ 6 M Cirrhosis ARV regimen DRVOther PI NNRTIOther Wyles DL. NEJM 2015, July 21, Epub ahead of print

 NS5B RAVs at baseline in 1/39 tested patients (C316H + V321I)  17% (33/198) of baseline sequences had NS5A polymorphisms at positions 28, 30, 31 or 93 Resistance data SVR 12 (n/N)*With baseline NS5A RAVsWithout baseline NS5A RAVs 12-week groups96% (22/23)98% (122/125) 8-week group67% (6/9)78% (31/40) Similar SVR 12 rates in patients with or without baseline NS5A RAVs  12 patients with relapse  10 in 8-week arm, 9/10 with concomitant DRV/r –2/10 relapses had baseline NS5A RAVs, 1 of which had also NS5B-V321I RAV –1/10 relapses in 8-week arm had an emergent NS5A RAV at time of failure (Q30E) –No other RAVs emergence at failure in the remaining 6 cases  2 in 12-week arm –1 had a NS5A RAV at baseline and failure (Y93N), and NS5B-L159F variant at failure –1 had emergence of NS5A-Q30R at failure ALLY-2 ALLY-2 Study: DCV + SOF for HCV in HIV co-infection Wyles DL. NEJM 2015, July 21, Epub ahead of print

12-Week Groups N = Week Group N = 50 Death01 (2%), unrelated Serious adverse event4 (3%), unrelated0 AEs leading to discontinuation00 Grade 3-4 laboratory abnormalities INR > 2 x ULN2 (1%)0 ALT > 5 x ULN00 AST > 5 x ULN01 (2%) Total bilirubin > 2.5 x ULN (all on ATV/r)7 (5%)1(2%) Lipase > 3.0 x ULN6 (4%)1 (2%) Adverse events and Grade 3-4 laboratory abnormalities, N (%) ALLY-2 ALLY-2 Study: DCV + SOF for HCV in HIV co-infection  2 HIV virologic failure, 1 unconfirmed with treatment discontinuation,  1 with HIV resuppressed with no ART adjustment Wyles DL. NEJM 2015, July 21, Epub ahead of print

12-Week Naïve N = Week Experienced N = 52 8-Week Naïve N = 50 Fatigue19% 8% Nausea14%15%8% Headache12%15%6% Diarrhea11%6%2% Vomiting6% 2% Rash6% 0 Insomnia5%6%0 Abdominal pain5%2% Cough3%2%6% Dizziness1%6%4% Constipation3%6%0 Clinical adverse events reported in ≥ 5% of patients in any group (%) ALLY-2 ALLY-2 Study: DCV + SOF for HCV in HIV co-infection Wyles DL. NEJM 2015, July 21, Epub ahead of print

ALLY-2 Study: DCV + SOF for HCV in HIV co-infection  Summary –After 12 weeks of DCV + SOF in HIV/HCV coinfected patients, the overall SVR 12 was 97% 97% in GT 1 ; 100% in GT 2, 3, and 4 97% in treatment-naive and 98% in treatment-experienced patients No significant effect of race, baseline HCV RNA levels, cirrhosis or ARV regimen –In patients treated for 8 weeks with DCV + SOF, SVR 12 was 76% –Increased relapse in coinfected patients with shorter therapy, higher baseline HCV RNA (≥ 2M IU/ml), and DRV/r-based cART with DCV 30 mg QD –No compromise of HIV suppression and no modification of on- treatment ARV regimens due to DCV + SOF –DCV + SOF was safe and well tolerated, offers a predictable drug-drug interaction profile with flexibility to dose adjust, and is compatible with a wide range of antiretrovirals ALLY-2 Wyles DL. NEJM 2015, July 21, Epub ahead of print