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AASLD 2011: Recombinant Hepatitis C Vaccine TG404 Shows Promise in Phase 2 Trial

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Transgene's recombinant poxvirus therapeutic hepatitis C virus (HCV) vaccine, TG4040, demonstrated good tolerability and increased the likelihood of viral suppression at 12 weeks when administered with pegylated interferon plus ribavirin, according to data from an international Phase 2 clinical trial reported at the American Association for the Study of Liver Diseases (AASLD) Liver Meeting last month in San Francisco.

Below is an edited excerpt from a Transgene press release summarizing the findings.

Transgene's Therapeutic HCV Vaccine TG4040 Combined with Commonly Used Treatment Achieves Substantial Viral Suppression in Randomized Phase II Trial

  • 64% cEVR in one experimental arm vs. 30% in the control arm
  • Multiple options for further clinical development

Strasbourg, France -- November 7, 2011 -- Transgene S.A. (Euronext Paris: FR0005175080) announces today the publication, during the AASLD congress (American Association for the Study of Liver Diseases), of interim data showing a substantial viral suppression at 12 weeks by using the combination of its therapeutic vaccine TG4040 with the commonly used treatment regimen in patients with chronic hepatitis C. These data were observed in a randomized Phase II trial that has included 153 patients (the "HCVac" study).

"The magnitude of improvement in early viral suppression observed in the HCVac trial is unheard of in the immunotherapy of this pathology" said Philippe Archinard, Chairman and CEO of Transgene. He added: "We will immediately start discussing with possible partners so as to envisage the future development of TG4040. Among the options, there is a strong rationale to go to treatment regimens without interferon".

The HCVac study is a three-arm (one control and two experimental arms with different schemes of administration) randomized Phase II trial evaluating the safety and efficacy of TG4040, a therapeutic vaccine, in combination with ribavirin ("RBV") and pegylated alpha interferon ("PegIFN"), the commonly used treatment regimen in the indication.

The study evidenced activity of the therapeutic vaccine in the two experimental arms with a substantial early viral suppression in arm C, with 64% of patients who achieved complete Early Virologic Response ("cEVR"), the primary endpoint of the study, compared to 30% in the control arm. The cEVR patients had no detectable viral load 12 weeks after the beginning of the treatment with PegIFN and RBV. The detection limit of the blood hepatitis C virus in the study was set at 10 IU/ml (using the Roche COBAS HCV TaqMan assay). The table below summarizes these findings:

 

Arm

Number of evaluable patients

cEVR (% of patients)

A (control)

30

30%

B (experimental)

61

46%

C (experimental)

53

64%*

*p=0.003

The experimental arms tested the same dosage of the therapeutic vaccine (107 pfu) injected subcutaneously under two different schemes of administration: in the arm B, the TG4040 dosage was administered 6 times and PegIFN and RBV were given 4 weeks prior to the initiation of TG4040 while in arm C the TG4040 dosage was administered 13 times and the PegIFN and RBV were introduced 12 weeks after the initiation of treatment with TG4040.

Two of the three adverse events reported on October 11, 2011 occurred in the experimental arm B, while one occurred in the experimental arm C. These adverse events are still under investigation. However, it could already be noted that: (i) TG4040 was administered at ten times higher dosage in the previous clinical trial (Phase I) without any of such adverse events reported, (ii) the 56 patients treated in the experimental arm C have received TG4040 in monotherapy (7 injections over 12 weeks) before PegIFN and RBV introduction and no such adverse events were observed during this monotherapy phase of the treatment and, finally, (iii) the three adverse events occurred in patients who received co-medications which could possibly have induced hematological toxicities independently of those usually documented with the usage of PegIFN and RBV.

Data were reported in a poster presented at AASLD that can be consulted at www.transgene.fr.

About TG4040:

Transgene's TG4040 vaccine candidate is a recombinant vector based on the MVA virus carrying and expressing three of the major non-structural proteins (NS3, NS4 and NS5B) of the hepatitis C virus ("HCV"). The MVA vector is a highly attenuated strain of vaccinia virus, which has been tested extensively in humans as a vaccine against smallpox and is known to strongly stimulate innate and adaptive immune responses to antigens.

About TG4040 clinical development program:

Phase I

Phase I clinical results in 39 treatment naive genotype 1 HCV patients showed that the product is safe and well tolerated at all dose levels tested. Immunological analyses on 15 treatment naive patients were encouraging and supported the expected mechanism of action of TG4040 which aims at inducing an effective HCV-specific T cell based immune response, able to control viral replication. Phase I data were published in the journal Gastroenterologyand reported in Nature Reviewsin 2011.

Phase II

The 153 patients in the HCVac study were recruited in five countries in Europe, in the United States and in Israel, and were randomized in the three arms of the study (one control arm without TG4040 and two experimental arms). HCVac investigates the efficacy and safety of two different schedules of administration of TG4040 administered in subcutaneous injections at the dose of 107 pfu in combination with PegIFN and RBV.

About Transgene:

Transgene, a member of the Institut Mérieux Group, is a publicly traded French biopharmaceutical company dedicated to the development of therapeutic vaccines and immunotherapeutic products in oncology and infectious diseases and has four compounds in Phase II clinical development: TG4010 and JX594/TG6006 having already completed initial Phase II trials, TG4001 and TG4040. Transgene has concluded strategic agreements for the development of two of its immunotherapy products: an option agreement with Novartis for the development of TG4010 to treat various cancers and an in-licensing agreement with US-based Jennerex, Inc. to develop and market JX594/TG6006, an oncolytic virus. Transgene has bio-manufacturing capacities for viral-based products. Additional information about Transgene is available at www.transgene.fr.

Investigator affiliations: Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany; Department of Infectious Diseases, Medical University of Silesia, Chorzow, Poland; Department of Internal Medicine, Medical University of Silesia, Katowice, Poland; Gr. T. Popa University of Medicine and Pharmacy, Institute of Gastroenterology and Hepatology, Iasi, Romania; Hepato-Digestive Unit, Strasbourg University Hospitals, Strasbourg, France; Foundation for the Study of Viral Hepatitis, Madrid, Spain; Division of Gastroenterology and Hepatology, Saint Louis University School of Medicine, Saint Louis, MO; Internal Medicine Clinic, Colentina Clinical Hospital, Bucharest, Romania; Department of Infectious Diseases and Hepatology, Medical University of Bialystok, Poland; Unit for the Clinical Management of Digestive Diseases and Ciberehd, Valme University Hospital, Sevilla, Spain; Department of Gastroenterlogy, Soroka Medical Center, Beersheba, Israel; Transgene, Illkirch, France; Transgene, Lyon, France; Transgene, Rockville, MD.

12/20/11

Reference

H Wedemeyer, E Janczewska-Kazek, WW Mazur, et al. HCVac study: Antiviral activity of TG4040 therapeutic vaccine in genotype-1 chronic HCV patients. 62nd Annual Meeting of the American Association for the Study of Liver Disease (AASLD 2011). San Francisco, November 4-8. 2011. Abstract 1336.

Other Source

Transgene S.A. Transgene's Therapeutic HCV Vaccine TG4040 Combined with Commonly Used Treatment Achieves Substantial Viral Suppression in Randomized Phase II Trial. Press release. November 7, 2011.