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# 9
Andrew Vaillant
Replicor Inc.
6100 Royalmount Avenue
Montreal, QC H4P 2
Canada
FUNCTIONAL REMISSION OF HBEAG NEGATIVE CHRONIC HBV INFECTION AFTER WITHDRAWAL OF COMBINED THERAPY WITH REP 2139 OR REP 2165, TENOFOVIR DISOPROXIL FUMARATE AND PEGYLATED INTERFERON Α-2A
Authors:
M. Bazinet4; V. Pantea5; G. Placinta5; I. Moscalu3; V. Cebotarescu; L. Cojuhari5; P. Jimbei2; L. Iarovoi2; V. Smesnoi2; T. Musteata2; A. Jucov3; A. Krawczyk1
Institution(s):
Universitätsklinikum Essen, Institute for Virology1;
Toma Ciorbǎ InfectiousClinical Hospital2;
ARENSIA Exploratory Medicine, Republican Clinical Hospital3;
Replicor Inc.4;
N.Testemitanu State University of Medicine andPharmacy5
Background:
The REP 401 protocol (NCT02565719) is a randomized, controlled trial
assessing the safety and efficacy of the nucleic acid polymers REP 2139 (lead clinical candidate) or REP 2165 combined with tenofovir disoproxil fumarate (TDF) and pegylated interferon α-2a (peg-IFN) in treatment naïve Caucasian patients with chronic HBeAg negative HBV infection.
Methods:
TDF monotherapy (24 weeks, 300mg PO qD) was followed by randomization into
experimental and control groups. Experimental patients received 48 weeks of TDF, peg-IFN (180ug SC qW) and REP 2139 or REP 2165 (250 mg IV infusion qW). Control patients receive 48 weeks of TDF + peg-IFN but crossover to 48 weeks of experimental therapy in the absence of a 3 log drop in HBsAg after 24 weeks of peg-
IFN. Viremia is monitored on the Abbott Architect and Realtime platforms.
Results:
Currently, 19/20 control patients have been crossed over and have completed ≥ 24
weeks of experimental therapy and 19/20 experimental patients have completed treatment and 4-12 weeks of follow-up. Therapy is well tolerated in all except in one crossover patient (REP 2165) who withdrew from therapy due to pegIFN-related depression.Following crossover in the control group, 10/10 patients (REP 2139) and 9/10 patients (REP 2165) have HBsAg reductions > 1 log from baseline. From these 19 responder patients, 14 have achieved HBsAg < 1IU/mL and 11 have achieved HBsAg ≤ 0.01 IU/mL. In the experimental group, 9/10 patients (REP 2139) and 8/10 patients (REP 2165) had HBsAg reductions > 1 log from baseline. From these 17 responder patients, 14 achieved HBsAg <1 IU/mL and 13 achieved HBsAg ≤ 0.01 IU/mL. HBsAg < 1 IU/mL in experimental patients was accompanied by profound increases in anti-HBs (93 to 223,055 mIU/mL) in 9/14 patients and strong therapeutic liver flares (ALT/AST> 5x ULN with normal synthetic liver function) in
12/14 patients. In control patients following crossover to NAP therapy, anti-HBs response is similar (69-68468 mIU/mL), however the strength of liver flares with similar HBsAg reductions were markedly attenuated.
Functional remission of HBV infection (HBsAg ≤ LLOQ, HBV DNA < LLOQ) is persisting 12-24 weeks after removal of therapy in 12 of 13 experimental patients achieving HBsAg <1 IU/mL (REP 2139: 8/10, REP 2165: 5/10). Control of HBV infection is stable in the 13th (REP 2139) patient (HBsAg 1.91 IU/mL, HBV DNA 93 IU/mL) at 24 weeks follow-up. Serum ALT/AST has normalized in all these patients. Rebound of infection has occurred in all other experimental patients during follow-up, however clinical benefit (reversal of HBV DNA rebound and normal ALT/AST) is apparent in two additional patients.
Conclusion:
NAPs are effective and well tolerated in combination with peg-IFN and TDF in HBeAg negative chronic HBV infection. REP 2139-based combination therapy elicits the
establishment of functional control of HBV infection persisting after removal of therapy (functional remission) in 80% of patients.
Disclosure:
Stock/Stock Options: Replicor Inc.
Management Position: Replicor Inc |
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楼主: 阳光醉人
发表于 2018-3-20 23:55
