HepeX-B和拉米混合治疗慢性乙肝有一定疗效

moonshadow

54th Annual Meeting of the American Association
for the Study of Liver Diseases
  October 24 - 28, 2003, Boston, MA  

Combined Therapy of HepeX-B and Epivir-HBV Is Effective in Chronic Hepatitis B


HepeX-B is a mixture of two human monoclonal antibodies directed against different epitopes of HBsAg that bind to all major HBV subtypes. In phase 1 clinical studies, HepeX-B was evaluated for safety, tolerability, and efficacy in 27 chronic HBV patients.

This phase II clinical study in Israel was designed to evaluate the safety and efficacy of a combined therapy of HepeX-B and lamivudine (Epivir-HBV) in chronic HBV patients. The rational behind this design was to use lamivudine to reduce the rate of replication within the infected cells together with antibodies that could clear viruses from blood circulation and prevent infection of new cells.

In addition, the combination of lamivudine with two monoclonal antibodies that bind different epitopes could potentially reduce the probability of developing escape mutants.



Sixty-two patients were randomized into five cohorts with different regimens of induction and maintenance doses of HepeX-B given in combination with lamivudine (100 mg daily) and compared to a placebo group given lamivudine alone.

Safety, results, and efficacy data were obtained from 48 patients who completed 3 months of dosing in a planned interim analysis.

Study Results

HepeX-B administration was not associated with any clinically significant adverse events (AEs) and was well tolerated in all dose groups.


A 50-80% decrease in concentrations of HBsAg was observed in patients from all dose groups following each infusion during the induction phase of the study when HepeX-B was administered one to three times weekly for 1 month.

No change in HBsAg was observed in placebo recipients. Serum HBsAg levels returned towards baseline during the interval preceding the next scheduled infusion. This pattern of suppression and rebound was observed around each infusion.



After the 30-day induction phase, in which HepeX-B was dosed more frequently, a maintenance regimen of 10 or 40 mg was administered monthly. In the maintenance phase, a similar pattern of response was observed for HBsAg.

While in the induction period, the frequent infusion maintained a sustained response; less frequent administration in the maintenance period was not sufficient to suppress HBsAg between infusions. Such a result suggests that more frequent dosing at the levels used in this study would prolong suppression of antigenemia in chronic patients who have active replication.


There was an inverse correlation between the increase in antibody levels post infusion and the decrease in HBsAg levels. Antibody excess result in sustained HBsAg response. Rebound in HBsAg was accompanied with a decrease in anti-HBs levels in all cases.



HBV DNA levels decreased during the induction phase. Overall, 59% of all subjects who received HepeX-B with lamivudine (23/39) had undetectable HBV DNA levels (below 50 copies/mL) at some time during the study compared to 50% of subjects who received lamivudine only (4/8).

In HBeAg-negative subjects, the response rate for undetectable HBV DNA was 75% among HepeX-B recipients (21/28) and 57% in lamivudine-only recipients (4/7).


Conclusions

Antibodies could be used to treat chronic HBV patients in combination with other antiviral therapies. Dose regimens and frequencies of administration should be optimized. Moreover, antibodies could serve as a stand-alone therapy in preventing re-infection of liver transplant patients associated with HBV. Such a study is being planned.

11/14/03

Reference
E Galun and others. A PHASE 2 CLINICAL STUDY EVALUATING SAFETY AND EFFICACY OF HEPEX-B, A MIXTURE OF TWO HUMAN MONOCLONAL ANTIBODIES TO HBSAG IN COMBINATION WITH LAMIVUDINE IN CHRONIC HBV PATIENTS. Abstract 1144 (poster). 54th Annual Meeting of the American Association for the Study of Liver Diseases. October 24-28, 2003. Boston, MA.  

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IC

Phase 2b study

IC

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