Transgene’s Therapeutic Vaccine TG4010 Meets Primary Endpoint in Non-small Cell Lung Cancer Phase IIb TrialSTRASBOURG, France, June 2, 2008 - Transgene today announced the successful results of the Phase IIb trial evaluating its therapeutic vaccine TG4010 (MVA-MUC1-IL2) as an adjunct to first line chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). These results will be presented today at the 2008 annual meeting of the American Society of Clinical Oncology in Chicago.
"We are very pleased that the data accumulated from the Phase IIb trial of our therapeutic vaccine TG4010 confirm the results we have previously observed in this indication and establish that the trial has met its primary endpoint”, said Philippe Archinard, Chief Executive Officer of Transgene. "These results clearly warrant pursuing development into a Phase III program and we will be seeking to establish a partnership in order to complete the last stages of clinical development and bring TG4010 to the market.”
The Phase IIb trial is a randomized, open label and controlled study designed to assess the efficacy of TG4010 in combination with cisplatin and gemcitabine compared to the chemotherapy regimen alone. The trial completed the enrolment of 148 patients at the end of May 2007 and was conducted in 27 centres located in France, Poland, Germany, and Hungary. The patients had NSCLC of all histology types including squamous cell carcinoma expressing MUC1, either stage IIIB with effusion (8%) or stage IV (92%), and had not received prior systemic treatment for their advanced disease. Half of the patients were randomized to receive the combination regimen of TG4010 vaccine plus chemotherapy (experimental arm). The other half of the patients received chemotherapy alone (control arm). The statistical primary endpoint is to observe at least 40% of patients free of progression six months after randomization in the experimental arm. Secondary endpoints are response rate, time to progression, overall survival, safety, immunological responses, proteomics, transcriptomics and genomics.The trial met its primary endpoint, with a progression-free survival (PFS) at six months of 44% (33 / 74 patients) in the experimental arm. In the control arm, PFS at six months is 35% (26 / 74 patients).Additionally, the response rate is substantially higher for the combination of TG4010 with chemotherapy compared to the chemotherapy alone. The response rates are 43% (32 / 74 patients) in the experimental arm and 27% (20 / 74 patients) in the control arm. The difference in favour of the experimental arm is statistically significant (p=0.03). Tumour responses were evaluated by an independent central review committee.
Time to progression is 5.8 months in the experimental arm and 5.2 months in the control arm. Median survival is 10.7 months for the experimental arm and 10.3 months for the control arm. Overall survival data is not yet mature. However, a trend for long-term survival is being observed in the experimental arm: after a follow-up of 13 months, 43% of the patients are still alive in the TG4010 plus chemotherapy arm compared to 33% in the control arm. Extended overall survival data will be available by the the end of the year.
A large biomarker exploratory program (immunology, proteomics, transcriptomics and genomics) is in progress to further characterize TG4010’s mode of action and contribute to the design of Phase III trials. Preliminary results show that in patients without elevated blood level of activated NK cells (“Natural Killers”, a group of cytotoxic lymphocytes) at baseline, i.e. 101 out of 138 evaluable patients, the median survival is 15.6 months in the experimental arm and 10.7 months in the control arm. Complete biomarker results should be available by the fourth quarter of 2008.
The trial confirmed the favourable safety profile of TG4010 when associated with chemotherapy: most adverse events observed so far were considered related to chemotherapy as well as to the underlying disease. Hematological toxicity was equivalent in both treatment groups. Most frequent adverse events related to TG4010 were injection site reactions and fever, which are classic vaccine-associated reactions. About TG4010 cancer vaccine TG4010 (MVA-MUC1-IL2) uses the Modified Vaccinia Ankara virus vector, a poxvirus that combines distinguishing advantages for an optimized systemic vaccination:
MVA is a highly attenuated strain which has been tested extensively in humans as a smallpox vaccine and is known to strongly stimulate innate and adaptive immune responses to antigens.
MUC1 is a major tumor-associated antigen that provides a viable target for vaccination.
TG4010 expresses the entire MUC1 gene sequence and has the potential to generate an immune response to all antigenic epitopes of MUC1.
The sequence coding for the cytokine Interleukin 2 (IL2) is included to help stimulate specific T-cell response. About the Phase IIb results presentation at ASCO 2008
The poster presentation and discussion will take on June 2nd, 2008 at the annual meeting of the American Society of Clinical Oncology, in Chicago (Abstract Nr. 8023, First author: Rodryg Ramlau, MD, PhD, Regional Lung Disease Hospital, Poznan, Poland).
The poster is available on Transgene’s website (http://www.transgene.fr>).About previous TG4010 clinical data in NSCLC
Transgene is a France-based biopharmaceutical company dedicated to the development of therapeutic vaccines and immunotherapeutic products in oncology and infectious diseases. The company has one product which has completed Phase II trials (TG4001/R3484), two compounds in Phase II trials (TG4010 and TG1042) and one compound in Phase I studies (TG4040). Transgene has concluded a strategic partnership agreement with Roche for the development of its TG4001/R3484 therapeutic vaccine to treat HPV-mediated diseases. Transgene has bio-manufacturing capacities for viral-based vectors and technologies available for out-licensing. Additional information about Transgene is available on the Internet at www.transgene.fr.
Cautionary note regarding forward-looking statements This press release contains forward-looking statements referring to seeking a partnership for and further developing one of Transgene’s therapeutic vaccine candidates. However, establishing a partnership and successfully pursuing product testing and development depend on a variety of factors, including identifying an appropriate partner, agreeing on financial and other partnership terms, and the technical performance of the product candidate in further testing. Results from future studies with more data may show less favourable outcomes than prior studies, and there is no certainty that product candidates will ever demonstrate adequate therapeutic efficacy or achieve regulatory approval or commercial use. For further information on the risks and uncertainties involved in the testing and development of Transgene’s product candidates, see Trangene’s Document de référence on file with the French Autorité des marchés financiers on its website and Transgene’s website. Investor contacts: Press contacts:
Transgene Capital MS&L
Philippe Poncet, Chief Financial Officer
Elisabetta Castelli, Head of Investor relations Mary Clark
Phone: + 33 3 88 27 91 21 Anna Mitchell
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t. +44 (0) 20 7307 5337 f. +44 (0) 20 7307 5331
Posted: June 2008