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Update on the safety and efficacy of REP 2139 monotherapy
and subsequent combination therapy with
pegylated interferon alpha-2a in chronic HBV / HDV
co-infection in Caucasian patients
Michel Bazinet1, Victor Pantea2, Valentin Cebotarescu2, Lilia
Cojuhari3, Paulina Jimbei3, Jeffrey Albrecht4, Peter Schmid4, Hadi
Karimzadeh5, Michael Roggendorf5, Andrew Vaillant1; 1Replicor
Inc., Montreal, QC, Canada; 2N. Testemitanu State University of
Medicine and Pharmacy, Chisinau, Moldova (the Republic of);
3Toma Ciorba Infectious Clinical Hospital, Chisinau, Moldova
(the Republic of); 4National Genetics Institute, Los Angeles, CA;
5Institure of Virololgy, Technische Universität München, Munich,
Germany
Introduction: HBV / HDV co-infection causes rapid progression
of liver disease and with no approved therapy, presents a
significant unmet medical need. Nucleic acid polymers (NAPs)
block HBV subviral particle assembly and release from infected
hepatocytes and can eliminate serum HBsAg. As the NAP REP
2139 was previously been shown to clear serum HBsAg and
improve the ability of immunotherapy to elicit SVR in Asian
patients with HBV, its activity in combination with Pegasys® in
HBV / HDV co-infected Caucasian patients is currently being
examined. Methods: In a phase II proof of concept trial (REP
301; NCT02233075), patients with chronic HBV / HDV co-infection
received once weekly dosing of 500mg REP 2139-Ca
(calcium chelate complex) by 2h IV infusion for 15 weeks,
followed by 15 weeks of combined therapy with 250mg REP
2139-Ca and 180ug Pegasys® and then 33 weeks with
Pegasys® monotherapy. Viremia (HDV RNA and HBV DNA),
HBsAg and anti-HBs are followed every two weeks (Robogene
RT-PCR, Abbott RealTime HBV, Abbott Architect) performed at
the Institute of Virology, University of Duisburg-Essen (Essen,
Germany). HDV RNA is validated on separate test platforms
at the National Genetics Institute (Los Angeles, USA) and the
Institute of Virology, Technische Universität München (Munich,
Germany). Results: REP 2139-Ca treatment is well tolerated
with mild and quickly resolving IV infusion reactions. Serum
HBsAg is currently reduced 1-6 log in 11/12 patients (5 with
serum HBsAg < 1 IU / ml) and HDV RNA is currently reduced
1.5-7 log in 12 /12 patients (undetectable in 6 patients). Anti-
HBs is detected in 10/12 patients, with 6 patients < 10mIU /
ml and after combined exposure to Pegasys®, 5 patients have
substantially increased anti-HBs titers from 50 to > 800 mIU /
ml. In all patients with pre-treatment HBV DNA < 10 IU / ml,
de-repression of serum HBV DNA is observed. Conclusions:
Updated interim data from the REP 301 protocol assessing the
safety and antiviral efficacy of REP 2139 (first in monotherapy
and then with add on Pegasys® at week 16) in 12 Caucasian
patients with chronic HBV / HDV co-infection demonstrated
substantial reductions in serum HBsAg and HDV RNA as well
as appearance of anti-HBs. HDV RNA reductions appear stronger
than HBsAg reductions, suggesting an additional antiviral
mechanism other than the inhibition of subviral particle assembly
may affect HDV directly. REP 2139-Ca may become an
important new therapeutic option for patients with chronic HBV
/ HDV infection.
Disclosures:
Michel Bazinet - Board Membership: REPLICor Inc.; Employment: REPLICor Inc.;
Management Position: REPLICor Inc.; Patent Held/Filed: REPLICor Inc.; Stock
Shareholder: REPLICor Inc.
Andrew Vaillant - Employment: REPLICor; Stock Shareholder: REPLICor
The following authors have nothing to disclose: Victor Pantea, Valentin
Cebotarescu, Lilia Cojuhari, Paulina Jimbei, Jeffrey Albrecht, Peter Schmid, Hadi
Karimzadeh, Michael Roggendorf
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楼主: disan
发表于 2015-10-5 12:18
