studies

HEPATOLOGY, VOLUME 62, NUMBER 1 (SUPPL) AASLD ABSTRACTS 557A
+ RBV (PR) ± first-generation PI. TE pts were further classified
as those who had relapsed after completing prior treatment
and those who experienced virologic failure (VF) on prior
treatment (eg, null or partial responders, or virologic breakthrough).
Results: With a 12-week regimen of GZR/EBR (no
RBV), SVR was achieved in 94% of TN pts (5% VF), 96% of
prior relapsers (0% VF) and 89% of prior on-treatment failures
(10% VF). With a 16- or 18-week (+ RBV) regimen, 95% of
prior on-treatment failures achieved SVR12 (0% VF). In each
group, efficacy was similar in noncirrhotic and cirrhotic pts
(Table 1). Baseline NS5A RAVs were uncommon (10%); however,
efficacy was lower in pts with baseline NS5A RAVs conferring
>5-fold shift in the potency of EBR in vitro, particularly
in TN pts with high viral load and in prior on-treatment failures
treated for 12 weeks. Conclusion: A 12-week regimen of GZR/
EBR (no RBV) is highly effective among GT1a-infected TN pts
and prior relapsers. A 16-week regimen of GZR/EBR (+ RBV) is
highly effective among TE GT1a-infected pts who experienced
virologic failure on prior treatment. Efficacy is similar in noncirrhotic
and cirrhotic pts.
Table 1
a Lost to follow-up, withdrew consent, discontinued due to adverse
event
b Excludes nonvirologic failures
Disclosures:
Alex J. Thompson - Advisory Committees or Review Panels: Gilead, Abbvie,
BMS, Merck, Spring Bank Pharmaceuticals, Arrowhead, Roche; Grant/Research
Support: Gilead, Abbvie, BMS, Merck; Speaking and Teaching: Roche, Gilead,
Abbvie, BMS
Stefan Zeuzem - Consulting: Abbvie, Bristol-Myers Squibb Co., Gilead, Merck
& Co., Janssen
Jürgen K. Rockstroh - Advisory Committees or Review Panels: Abbvie, BI, BMS,
Merck, Roche, Tibotec, Abbvie, Bionor, Tobira, ViiV, Gilead, Janssen; Consulting:
Novartis; Grant/Research Support: Merck; Speaking and Teaching: Abbott,
BI, BMS, Merck, Roche, Tibotec, Gilead, Janssen, ViiV
Paul Y. Kwo - Advisory Committees or Review Panels: Abbvie, Abbott, Novartis,
Merck, Gilead, BMS, Janssen; Consulting: BMS; Grant/Research Support:
Roche, Abbvie, Merck, BMS, Abbott, Idenix, Vital Therapeutics, Gilead, Vertex,
Merck, Idenix; Speaking and Teaching: Merck, Merck
David Roth - Advisory Committees or Review Panels: Merck, Sharp and Dome;
Consulting: Merck, Sharp and Dome
Eric Lawitz - Advisory Committees or Review Panels: AbbVie, Achillion Pharmaceuticals,
Regulus, Theravance, Enanta, Idenix Pharmaceuticals, Janssen, Merck
& Co, Novartis, Gilead; Grant/Research Support: AbbVie, Achillion Pharmaceuticals,
Boehringer Ingelheim, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmith-
Kline, Idenix Pharmaceuticals, Intercept Pharmaceuticals, Janssen, Merck & Co,
Novartis, Nitto Denko, Theravance, Salix, Enanta; Speaking and Teaching: Gilead,
Janssen, AbbVie, Bristol Meyers Squibb
Mark S. Sulkowski - Advisory Committees or Review Panels: Merck, AbbVie,
Janssen, Gilead, BMS; Grant/Research Support: Merck, AbbVie, Janssen, Gilead,
BMS
Xavier Forns - Consulting: Jansen, Abbvie; Grant/Research Support: Jansen,
Gilead
Janice Wahl - Employment: Merck & Co,
Bach-Yen T. Nguyen - Employment: Merck
Eliav Barr - Employment: Merck
Anita Y. Howe - Employment: Merck Research Laboratory
Michael D. Miller - Employment: Merck & Co., Inc.; Stock Shareholder: Merck
& Co., Inc.
Peggy Hwang - Employment: Merck, Merck
Michael Robertson - Employment: Merck; Stock Shareholder: Merck
704
Prevention of allograft HCV reinfection with peri-transplant
MBL-HCV1 monoclonal antibody in combination
with oral direct-acting antiviral
Parvez S. Mantry 1 , Heidi L. Smith 2 , Raymond T. Chung 3 , William
C. Chapman 4 , Michael P. Curry 5 , Thomas D. Schiano 6 , Yang
Wang 2 , Deborah C. Molrine 2 ; 1 The Liver Institute, Methodist Dallas
Medical Center, Dallas, TX; 2 MassBiologics of the University
of Massachusetts Medical School, Boston, MA; 3 Department of
Gastroenterology, Massachusetts General Hospital, Boston, MA;
4 Department of Surgery, Washington University, St. Louis, MA;
5 Division of Gastroenterology, Beth Israel Deaconess Medical Center,
Boston, MA; 6 Recanati-Miller Transplantation Institute, Mount
Sinai Medical Center, New York, NY
Background Patients with hepatitis C viremia at the time of
liver transplantation experience rapid infection of the donor
allograft, increased risk of graft failure, and accelerated rates
of fibrosis. To evaluate a peri-transplant treatment strategy to
prevent allograft hepatitis C virus (HCV) infection, MBL-HCV1,
a neutralizing human monoclonal antibody (mAb) targeting a
conserved linear epitope of the HCV envelope, was combined
with licensed direct-acting antivirals (DAA) in an open-label
exploratory efficacy trial. Methods All subjects had HCV RNA
titers > 10 4 IU/mL at the time of transplantation. MBL-HCV1
was dosed intravenously at 50 mg/kg, beginning just prior to
the anhepatic phase of the transplantation procedure. Subjects
received three mAb infusions on the day of transplant and
daily infusions on days 1-7 post-transplantation. Oral DAA therapy
was initiated between days 3 and 7 with documentation
of adequate graft function and administered in combination
with weekly mAb infusions through day 28. During the second
post-transplant month, MBL-HCV1 was administered bi-weekly
while continuing oral DAA therapy; study treatment could be
extended until day 84 (12 weeks) post-transplant in subjects
whose HCV RNA remained undetectable. In Part 1 of the study,
eight subjects received MBL-HCV1 in combination with telaprevir
for up to 12 weeks. In Part 2 of the study, two subjects
have received MBL-HCV1 in combination with sofosbuvir for
12 weeks. Results In Part 1 of the study, prolonged aviremia
was observed in 5 of 8 subjects and one subject (12.5%) had
a sustained virologic response (SVR24). There were 11 serious
adverse events assessed as unrelated to study treatment. In Part
2 of the study, both subjects (100%) achieved SVR12 and the
first subject has completed the 24 week visit with an SVR. One
subject had a history of prior virologic breakthrough on interferon
therapy, while the other previously experienced virologic
relapse following a 12 week pre-transplant course of sofosbuvir/simeprevir.
With MBL-HCV1 plus sofosbuvir treatment,
both subjects were aviremic by day 21 post-transplantation.
Two serious adverse events were reported > 2 months after
completion of study treatment and assessed as unrelated to
study treatment. Conclusions Peri-transplant therapy with MBL-
HCV1 in combination with an oral DAA is capable of preventing
post-transplant HCV recurrence and the combination
of MBL-HCV1 with sofosbuvir appears promising. Given the
observed viral kinetics, this treatment approach has the potential
to achieve viral eradication in the immediate post-transplant
period, thereby mitigating the risks of severe allograft HCV
infection.