studies

262A AASLD ABSTRACTS HEPATOLOGY, October, 2015
idly. Our objective was to project the number of HCV patients
needing treatment in 2015 and beyond, and the long-term
health outcomes under different treatment penetration rates.
Method: We used our previously published Hepatitis C Disease
Burden Simulation model (HEP-SIM), which projected the
changing prevalence of HCV in the United States. The HEP-SIM
model was validated with NHANES studies and other published
data. We simulated the current clinical management of
HCV from 2001 onwards, which included risk-based screening
until 2013 and addition of birth-cohort screening afterwards.
We modeled antiviral treatment in different waves starting with
peginterferon-ribavirin (PEG-RBV) until 2011, followed by the
launch of boceprevir/telaprevir in 2012, sofosbuvir/simeprevir
in 2014, and finally oral DAAs in 2015. We also implemented
changes in insurance status because of the Affordable Care
Act. We projected the number of patients needing treatment
in 2015 and beyond under varying treatment capacity/penetration
scenarios. We also projected patients’ fibrosis score,
HCV awareness status, and access to insurance. Results: We
estimated that in 2015, 2 million noninstitutionalized patients
would be chronically infected and viremic. Among these
patients, 1.1 million would be potential DAA candidates, i.e.,
aware of their HCV status and insured. At the current annual
treatment capacity of 200,000 patients, it will take at least 10
years to treat the majority of the patients. By 2025, the number
of treatment candidates would decline to fewer than 50,000
patients. Even in the DAA era, 320,000 patients would die
because of HCV, 32,000 patients would get liver transplants,
202,000 would develop decompensated cirrhosis (DC) and
156,000 would progress to hepatocellular carcinoma (HCC)
by 2050. Doubling the annual treatment capacity could avoid
8,000 deaths, 700 transplants, 7,000 DC and 4,000 HCC
cases by 2050. Conclusions: Though the majority of patients
aware of their HCV will be treated in the next 10 years, the
HCV burden would still remain substantial unless aggressive
screening and treatment policies are implemented. Increasing
HCV treatment capacity is essential to decrease disease burden
and improve health outcomes of HCV patients in the US, and
decrease health resource utilization.
Disclosures:
Jagpreet Chhatwal - Consulting: Merck & Co., Inc., Gilead, Complete HEOR
Solutions; Grant/Research Support: NIH/National Center for Advancing Translational
Sciences
The following authors have nothing to disclose: Xiaojie Wang, Fasiha Kanwal,
Mina Kabiri, Turgay Ayer, Julie M. Donohue, Mark S. Roberts
105
An international, phase 2 randomized controlled trial of
the dual PPAR α-δ agonist GFT505 in adult patients with
NASH
Vlad Ratziu 1 , Stephen A. Harrison 2 , Sven M. Francque 3 , Pierre
Bedossa 4 , Lawrence Serfaty 5 , Manuel Romero-Gomez 6 , Paul
Cales 7 , Manal F. Abdelmalek 8 , Stephen H. Caldwell 9 , Joost
Drenth 10 , Quentin M. Anstee 11 , Dean W. Hum 12 , Rémy Hanf 12 ,
Alice Roudot 12 , Sophie Megnien 12 , Bart Staels 13 , Arun J. Sanyal 14 ;
1 Hepatology, Hopital Pitie Salpetriere, Paris, France; 2 Department
of Medicine, Gastroenterology & Hepatology Service,, Brooke
Army Medical Center, Fort Sam Houston, TX; 3 Department of Gastroenterology
& Hepatology, Antwerp University Hospital, University
of Antwerp, Antwerp, Belgium; 4 Department of Pathology,
Hôpital Beaujon, University Paris-Denis Diderot, Clichy, France;
5 Service d’Hépatologie,, Hôpital Saint-Antoine, APHP, UPMC Paris
6, Paris, France; 6 Hospital Universitario de Valme, Unit for the
Clinical Management of Digestive Diseases and CIBERehd, Sevilla,
Spain; 7 Hepatology Department, University Hospital & LUNAM
University, Angers, France., Angers, France; 8 Duke University,
Duke university, Durham, NC; 9 University of Virginia, Gastroenterology
& hepatology Division, Charlottesville, VA; 10 Radboud
University Medical Center, Department of Gastroenterology and
Hepatology, Nijmegen, Netherlands; 11 Institute of Cellular Medicine,,
Faculty of Medical Sciences, Newcastle University, Newcastle
upon Tyne, United Kingdom; 12 Genfit SA, Loos, France;
13 Université Lille 2, INSERM U1011, European Genomic Institute
for Diabetes (EGID), Institut Pasteur de Lille, Lille, France, Lille,
France; 14 Virginia Commonwealth University, Richmond, VA
Peroxisome proliferator-activated receptor α-δ dual agonists,
such as GFT505, are a promising therapy for NASH as they
improve hepatic insulin sensitivity, glucose homeostasis, lipid
metabolism, and inflammation. Methods. In this randomized
controlled trial (56 European and US centers) 274 patients (pts)
(full analysis set, FAS) with histologically-defined non-cirrhotic
NASH received GFT505 80 mg or 120 mg QD vs placebo (PLB)
for one year. The primary outcome was resolution of NASH
without worsening of fibrosis. Data were analyzed according
to baseline severity (histological NAS score) and center effect.
Biopsies were read by a single pathologist. Results. 237 pts
had entry and end-of-treatment biopsies (ITT population). While
the a priori primary endpoint did not meet significance, after
controlling for baseline severity and center effect, pts in the
120 mg arm had a 1.94 (CI 1.08-3.48, p=0.027) higher relative
risk (RR) of achieving the primary end-point compared to
PLB, while the RR was 1.68 (0.92-3.05, p=0.091) for the 80
mg arm. Results were similar in the FAS where pts missing the
second biopsy were counted as failures. In pts with moderate
activity (NAS 4 or 5) the response rate was 27.5% in the 120
mg arm vs. 19.5% for the PLB arm. In those with severe activity
(NAS>5) it was 14.8% vs. 0%, respectively. In the 120 pts
with NAS>4 from centers that recruited >1 patient/arm, the
response rate was 29% and 5% in the 120 mg and PLB arms,
respectively, p=0.01. A >2 point NAS reduction was obtained
in 48% and 21% of patients respectively, p=0.01. Compared
to PLB, the 120 mg arm improved ballooning (45% vs. 23%,
p=0.02), inflammation (55% vs. 33%, p=0.05) and steatosis
(35.5% vs. 18%, NS). In the 120 mg arm, resolution of NASH,
resulted in a significant improvement in fibrosis (mean change
-0.67 vs. +0.09 in non-responders, p