1. Study 337-1119: LDV/SOF in genotype 5
Design
Open-label
W12
≥ 18 years
Chronic HCV infection
Genotype 5
HCV RNA ≥ 10,000 IU/ml
Treatment-naïve or experienced
Compensated cirrhosis allowed
Creatinine clearance ≥ 60 ml/min
No HBV or HIV co-infection
N = 41
LDV/SOF
SVR12
Co-formulated ledipasvir-sofosbuvir (LDV 90 mg/SOF 400 mg): 1 pill QD
Objective
Primary endpoint: SVR12 (HCV RNA < 15 IU/ml), with 2-sided 95% CI
Abergel A. Lancet Infect Dis. 2016;16:459-64

2. Study 337-1119: LDV/SOF in genotype 5
Baseline characteristics, patient disposition and outcome
Treatment- naïve
N = 21
Treatment-experienced
N = 20
Mean age, years 61 64
Female
48%
50%
Body mass index < 30 kg/m2
100%
85%
HCV RNA log10 IU/ml, mean
6.2
6.6
Cirrhosis
14%
30%
IL28B CC genotype
62%
Previous HCV treatment response
Relapse/breakthrough
Non-response
Intolerance to IFN -
70%
25% 5%
Creatinine clearance (Cockroft-Gault), ml/min, mean
85.4
85.1
Discontinuation, N
SVR12 (95% CI)
Relapse, N
95% (76-100) 1
95% (75-100)
Abergel A. Lancet Infect Dis. 2016;16:459-64

3. Study 337-1119: LDV/SOF in genotype 5
Adverse events, N (%)
N = 41
Any adverse events
33 (80)
Serious adverse events
1 (2) : depression
Treatment discontinuation due to adverse event
Adverse events in ≥ 5% of patients
Asthenia
39%
Headache
27%
Fatigue
10%
Upper abdominal pain 7%
Arthralgia
Diarrhea
Dizziness
Musculoskeletal pain
Myalgia
Nasopharyngitis
Urinary tract infection
Cough 5%
Abergel A. Lancet Infect Dis. 2016;16:459-64

4. Study 337-1119: LDV/SOF in genotype 5
Additional outcome
No grade 3 or 4 laboratory abnormalities
Emergent laboratory abnormalities: total bilirubin < 1.5 ULN: 10% ; hemoglobin g/dl: 2% ; lipase > ULN: 2% ; platelets to /mm3: 2%
Successful deep sequencing in 39/41 patients
NS5A: 8/39 (21%) had RAVs at baseline (SVR12 in 7/8 patients)
Q30R/L (N = 2 ; 2.5% and 3.9% of viral population)
L31M/F (N = 4 ; 29.5% to > 99% of viral population)
P58S (N = 2 ; 9.9% and 94.6% of viral population)
NS5B: 9/39 (23%) had RAVs at baseline (SVR12 in 9/9 patients)
N142T (N = 7 ; 1.1% to 19.2% of viral population)
M289I (N = 2 ; 7.6% and 98.3% of viral population)
Abergel A. Lancet Infect Dis. 2016;16:459-64

5. Study 337-1119: LDV/SOF in genotype 5
Viral relapse (n = 2)
Man, 72-year old, treatment-experienced (partial response), IL28B TT genotype, cirrhosis, HCV RNA IU/ml. At baseline: NS5A RAV L31M (> 99% of viral population). HCV RNA < limit of quantification at W1 and undetectable from W2 to the end of treatment. Relapse at post-treatment W4
At relapse
NS5A: L31M, no additional RAV
NS5B: emergence of S282T (2% viral population) and M289I (16% viral population)
Woman, 56-year old, naïve, no cirrhosis, IL28B TT genotype, HCV RNA UI/ml. HCV RNA < limit of quantification at W1 and undetectable from W2 to the end of treatment. Relapse at post-treatment W4. Failure to baseline and post-treatment NS5A and NS5B amplification
Abergel A. Lancet Infect Dis. 2016;16:459-64

6. Study 337-1119: LDV/SOF in genotype 5
Summary
This prospective, open-label study is the first to assess a regimen consisting of only directly acting antivirals in patients with HCV genotype 5 infection
A fixed-dose combination regimen with ledipasvir-sofosbuvir once per day for 12 weeks resulted in SVR12 in 39 (95%) of 41 patients
The 2 relapses had the IL28B TT genotype, one was naïve with no cirrhosis, one was treatment-experienced with cirrhosis and NS5A RAV L31M at baseline
Overall, the presence of NS5A RAVs and NS5B N142T and M289I had no meaningful effect on the SVR12 for LDV/SOF in genotype 5
No patients discontinued treatment because of an adverse event. Only one serious adverse event, worsening depression, was reported, and was deemed to be unrelated to study treatment
Abergel A. Lancet Infect Dis. 2016;16:459-64