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New Drug HepeX-B To Prevent HBV Post-Transplant Reinfection
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Cubist Pharmaceuticals Reports Results From Phase 2 Study Hepex-B(TM), Which Was Licensed From XTLbio
REHOVOT, Israel, December 22 /PRNewswire-FirstCall/ -- XTL
Biopharmaceuticals Ltd. ("XTLbio") (LSE: XTL; NASDAQ: XTLB; TASE: XTL) announces that Cubist Pharmaceuticals, Inc. (Nasdaq: CBST) today provided data from a recently concluded Phase 2 study of HepeX-B(TM) which was licensed to Cubist by XTLbio in 2004. In the Phase 2 study, HepeX-B was studied as maintenance therapy to prevent reinfection with hepatitis B in patients with liver transplants. Data from liver transplant patients who were
treated with monthly infusions of 20 or 40 mg HepeX-B versus 5000 IU of HBIg showed that patients with either dose of HepeX-B experienced no evidence of viral reinfection. The data also showed fewer and less serious adverse experiences reported in both HepeX-B groups as compared to the HBIg group,
although the differences were not statistically significant given the number of patients in the trial. Patients who were treated with HepeX-B as well as HBIg also received concurrent HBV polymerase inhibitor. Cubist will be reviewing Phase 2 results with the U.S. Food and Drug Administration (FDA) early in 2006.
The data released today is derived from patients who have completed at least 6 months of therapy, which was the treatment duration at which the primary endpoint was measured. Eleven patients received monthly 20 mg infusions of HepeX-B; ten received monthly infusions of 40 mg HepeX-B; and nine received monthly infusions of 5000 IU HBIg (current standard of care).
Cubist recently met with the FDA to discuss proposed changes to the method of manufacture and formulation of HepeX-B. Specifically, Cubist plans to shift from the use of hybridoma cells to Chinese Hamster Ovary (CHO) cells and to switch to subcutaneous delivery prior to Phase 3. The objective of the manufacturing change is to provide a stable platform for commercialization.
The switch to subcutaneous administration is meant to increase patient convenience and compliance with chronic therapy. Cubist will meet again with the FDA in early 2006 to discuss the implications of these changes on the next stage of the clinical program.
Michael S. Weiss, Chairman of XTLbio, commented: "We are very pleased with the results of this Phase 2 trial and the fact that reinfection was not observed in any of the patients treated with HepeX-B. We are proud of being responsible for HepeX-B's discovery and early clinical development, and we
are pleased with the progress of this product towards commercialization in the hands of our partner Cubist."
About Hepatitis B (HBV)
The hepatitis B virus, according to Datamonitor, has infected more than 2 billion people around the world. Although a vaccine against HBV was introduced in 1982, globally, 350 million people are infected chronically with the disease and approximately 1 million people die each year as a result of complications from HBV infection. Current treatment regimens for chronic HBV often include use of interferon alpha or an antiviral drug. Despite these
treatment options, chronic HBV can lead to severe liver damage and patients may require liver transplantation. To prevent re-infection of the new liver with HBV, patients are currently treated with hepatitis B immune globulin (HBIg) combined with an antiviral compound, such as Lamivudine. The global market for HBIg is estimated to be about $100 million annually.
About HepeX-B(TM)
HepeX-B is a combination of two fully human monoclonal antibodies that target HBV surface antigens. It is currently in evaluation for the prevention of infection by HBV in liver transplant patients who have been maintained on HBIg. HepeX-B already has been granted Orphan Drug Status in both the U.S. and the European Union.
About XTLbio
XTL Biopharmaceuticals Ltd (XTLbio) is engaged in the research,
development and commercialization of therapeutics for the treatment of infectious diseases, with a particular focus on hepatitis C. XTLbio's most advanced therapeutic in Hepatitis C is XTL-6865 - a combination of two monoclonal antibodies against the hepatitis C virus - presently in Phase 1 clinical trials in patients with chronic hepatitis C. XTLbio's second Hepatitis C therapeutic is XTL-2125 - a small molecule inhibitor of the hepatitis C Virus polymerase - expected to enter Phase 1 clinical trials in 1H2006. XTLbio hepatitis C pipeline also includes several families of pre-clinical hepatitis C small molecule inhibitors. In 2004, XTLbio licensed HepeX-B - an antibody therapeutic against hepatitis B - to Cubist Pharmaceuticals. XTLbio is publicly traded on the London, NASDAQ, and Tel-Aviv Stock Exchanges (LSE: XTL; NASDAQ: XTLB; TASE: XTL).
XTL-6865 To prevent Hepatitis C Reinfection Following Liver Transplant
Preventing Re-infection following Liver Transplant
Hepatitis C is the leading cause of liver transplants in the U.S. It is estimated that in 2004, over 2,000 liver transplants were performed in the U.S. in HCV positive patients. Although the HCV infected liver is removed during the transplant procedure, the newly transplanted healthy liver is re-infected with HCV from the patient's serum. Re-infection occurs in all patients within days following the transplant. Recurrent HCV infection is the leading cause of graft failure: 10% of patients will die (or be re-transplanted) by year five due to recurrent HCV disease. A further 30% of patients will have cirrhosis at the end of year five.
There is no therapy available to prevent re-infection following a liver transplant. Once the liver has been re-infected, clinicians attempt to treat the recurrent disease. Response rate to this treatment is low (~20%). Therefore, re-infection following a liver transplant represents a significant unmet medical need.
One of the potential indications of XTL-6865 is preventing re-infection following a liver transplant. We estimate that a successful therapy for preventing re-infection with HCV following liver transplantation could reach annual worldwide sales of approximately $400 million.
XTL-6865 is being developed by XTLbio to prevent hepatitis C re-infection following a liver transplant and for the treatment of chronic HCV. XTL-6865 is a combination of two fully human monoclonal antibodies (Ab68 and Ab65) against the hepatitis C virus E2 envelope protein. A single antibody version of this product, then referred to as HepeX-C, was tested in a pilot clinical program that included both Phase I and Phase II clinical trials. In April 2005, we submitted an IND to the FDA in order to commence a Phase Ia/Ib clinical trial later this year for XTL-6865, the dual-MAb product.
The two antibodies comprising XTL-6865 were selected by screening a large panel of candidates based on their high level of activity against the virus in our proprietary HCV models. We believe that a combination of two antibodies that bind to different epitopes is essential to provide broad coverage of virus quasispecies, and to minimize the probability for escape from therapy. We have shown that the two antibodies chosen (Ab68 and Ab65) specifically bind and immunoprecipitate viral particles from infected patients' sera with different HCV genotypes. In addition, both antibodies reduced mean viral load in HCV-Trimera mice. We have also shown that incubation of an infectious human serum with Ab68 or Ab65 prevented the serum's ability to infect human liver cells and human liver tissue.
The single antibody HepeX-C product candidate (Ab68) was tested in a pilot clinical program, which included:
* A Phase Ia/Ib Clinical Program in Patients with Chronic HCV, which demonstrated the safety and tolerability of using single and multi-doses of Ab 68 up to 120mg for a 28 day dosing period. In terms of efficacy, eight out of 25 patients had at least a 90% reduction in HCV-RNA levels from pre-treatment levels following administration of Ab68. These trials provided safety data, as well as a preliminary indication of anti-viral activity in humans.
* A Phase IIa Clinical Trial with Ab68 Following Liver Transplant, which demonstrated the safety and tolerability of Ab68 up to 240mg dosed for 12 weeks. Higher doses were not tested due to a clinical hold as a result of an intraoperative death of the first patient tested at the 480mg dose level (later determined by the medical examiner to be related to pulmonary emboli (blood clots in the lung)). The FDA later cleared the clinical hold, but we decided to discontinue the study and focus further development efforts on the dual anti-body product, XTL-6865. No other drug-related serious adverse events were reported during this study. The 120mg and 240mg dose groups had a significantly greater reduction in viral load than the placebo group during the first week when dosed daily. This effect was less evident when dosed less frequently than daily. This data provided additional evidence of anti-viral activity in immunosuppressed patients.
Based on this information, we had a pre-IND meeting with the FDA in October 2004 regarding XTL-6865, at which we presented data on Ab68 and Ab65, which had just successfully completed pre-clinical development. In April 2005, we submitted an IND to the FDA in order to commence a Phase Ia/Ib clinical trial later this year for XTL-6865, the dual-MAb product.
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