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AASLD2017[930]
Safety and Efficacy of Vesatolimod (GS-9620)
in Patients with Chronic Hepatitis B (CHB) Who
Are Not Currently on Antiviral Treatment
Kosh Agarwal1, Sang Hoon Ahn3, Magdy Elkhashab2, Kyungpil
Kim4, Audrey H. Lau4, Anuj Gaggar4, Mani Subramanian4,
John G. McHutchison4, Pietro Andreone5, Hyung J. Kim6, Wan-
Long Chuang7, Mindie H. Nguyen8; 1Institute of Liver Studies,
King’s College Hospital, London, United Kingdom; 2Toronto
Liver Centre, Toronto, ON, Canada; 3Yonsei University Health
System, Seoul, Korea (the Republic of); 4Gilead Sciences, Inc.,
Foster City, CA; 5Dipartimento di Scienze Mediche e Chirurgiche,
Centro di Ricerca per lo Studio delle Epatiti, University
of Bologna, Bologna, Italy; 6Chung-Ang University Hospital,
Seoul, Korea (the Republic of); 7Kaohsiung Medical University
Chung-Ho Memorial Hospital, Kaohsiung, Taiwan; 8Stanford
University, Palo Alto, CA
Background: Vesatolimod is an oral agonist of Toll-like
receptor 7 designed for presystemic activation to minimize
systemic exposure and side effects from Vesatolimod treatment.
We evaluated Vesatolimod in CHB patients who are
not currently on antiviral treatment (OAV). Methods: In
this multicenter phase 2 study, 192 patients were randomized
2:2:2:1 to receive Vesatolimod (at doses of 1 [n=53],
2 [n=56], and 4 [n=55] mg) or placebo once weekly for
12 weeks; all subjects also received TDF 300 mg daily for
48 weeks. At screening, patients had HBV DNA ≥2000 IU/
mL, were non-cirrhotic and not on OAV; patients were
stratified by HBeAg status and ALT level. Quantitative
serum HBsAg (Abbott Architect Assay) decline at Week 24
from baseline was estimated using mixed effect model for
repeated measures. Periodic peripheral blood evaluation
of cytokines and ISG transcripts were performed in addition
to safety assessments (e.g. adverse events [AEs] and
laboratory abnormalities). Results: Baseline demographics
were similar across all dosing groups (table). Among Vesatolimod-
treated patients receiving 1, 2, or 4 mg: Grade 3
AEs (no Grade 4) and any AE leading to discontinuation
were observed in 0%, 4%, and 7% of patients respectively
while serious AEs were observed in 2%, 0%, and 2% respectively.
Patients with any AEs were dose-dependent and
higher in the Vesatolimod groups compared to placebo
(table). ISG15 induction was dose-dependent (table) and
did not correlate with HBsAg changes. No dose-dependent
induction of interferon-alpha was observed. HBV DNA
suppression rates were similar across all treatment arms
by Week 24, and 1 subject had HBeAg loss (2mg group).
No significant differences in mean HBsAg changes from
baseline were observed between Vesatolimod-treated and
placebo groups; no patients experienced HBsAg loss. At
Week 24, HBsAg declines of ≥0.5 log10 were observed in
11% (placebo) and 4% (1 mg), 11% (2 mg), and 4% (4
mg) in Vesatolimod-treated patients. Conclusions: Overall,
Vesatolimod is safe and well-tolerated in CHB patients.
While consistent dose-dependent pharmacodynamic
induction of ISGs was demonstrated it did not result in
significant HBsAg decline. Longer term evaluation in these
patients through Week 48 is currently ongoing.
Disclosures:
Kosh Agarwal - Advisory Committees or Review Panels: Merck, AbbVie,
Gilead; Grant/Research Support: BMS, Gilead; Speaking and Teaching:
Gilead, Merck, Abbvie
Magdy Elkhashab - Advisory Committees or Review Panels: Abbvie Inc,
Gilead Sciences, Merck; Grant/Research Support: Gilead Sciences, Abbvie
Inc, Intercept, EISAI, Roche, Celgene, Genfit, Shire, Spring Bank, Janssen
Audrey H. Lau - Employment: Gilead Sciences, Inc; Stock Shareholder:
Gilead Sciences, Inc.
Anuj Gaggar - Employment: Gilead Sciences, Inc.
Mani Subramanian - Employment: Gilead Sciences; Stock Shareholder:
Gilead Sciences
John G. McHutchison - Employment: Gilead; Stock Shareholder: Gilead
Pietro Andreone - Advisory Committees or Review Panels: Intercept,
Gilead, MSD/Schering-Plough, Abbvie; Grant/Research Support: BMS, MSD/
Schering-Plough, Abbvie
Wan-Long Chuang - Advisory Committees or Review Panels: Gilead, BMS,
Abbvie, MSD, PharmaEssentia; Speaking and Teaching: BMS, Gilead, MSD,
Abbvie, PharmaEssentia, Roche
Mindie H. Nguyen - Advisory Committees or Review Panels: Dynavax
Laboratories, Gilead Sciences, Inc., Alynam Pharmaceuticals, Intercept
Pharmaceuticals; Grant/Research Support: Gilead Sciences, Inc., Bristol-
Myers Squibb, Janssen Pharmaceuticals
The following people have nothing to disclose: Sang Hoon Ahn
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发表于 2017-10-19 17:26