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Trabedersen shows good safety, tolerability and promising survival in patients with pancreatic carcinoma, malignant melanoma and colorectoral carcinoma

Antisense Pharma announces new data on its lead compound at ASCO 2009, including the design of the Phase III SAPPHIRE study currently ongoing in high-grade glioma 

ORLANDO - June 2nd 2009 - Trabedersen (AP 12009), a first in class investigational therapy for the treatment of aggressive tumors, showed a good safety and tolerability profile and encouraging survival data in patients with pancreatic carcinoma, malignant melanoma and colorectal carcinoma. Data from a Phase I/II study, announced at the American Society of Clinical Oncology (ASCO) 2009, will lead to further clinical studies. Currently an additional 24 patients with pancreatic carcinoma or malignant melanoma are being recruited to confirm the promising efficacy and safety results with trabedersen. (Abstract 4619)
Additional details concerning the design of the ongoing SAPPHIRE Phase III study were also announced at the meeting. SAPPHIRE is a randomized, active-controlled, clinical Phase III trial to confirm the efficacy and safety of trabedersen in recurrent or refractory anaplastic astrocytoma (AA, brain tumor, WHO grade III).
Trabedersen has already shown a clear survival benefit in a randomized, active-controlled clinical Phase IIb study in high-grade glioma (HGG) patients, compared to standard chemotherapy. (Abstract 2037)

Interim results of Phase I/II study
In the trial, 33 patients with advanced pancreatic carcinoma, malignant melanoma or colorectal carcinoma were treated intravenously with trabedersen in two different treatment schedules. The primary objective of the study was to determine the maximum tolerated dose (MTD) and the secondary objectives were to investigate the safety and tolerability of trabedersen, its pharmacokinetics and antitumor activity.

Very good safety and tolerability of trabedersen was observed in the study, with moderate self-limiting thrombocytopenia the main adverse event seen. The MTD was established as 160 mg/m²/d in the first treatment schedule; MTD has not yet been reached in the second treatment schedule.

Survival data were encouraging. Of the five malignant melanoma patients treated with trabedersen, one from the first schedule showed stable disease and lived for 13.8 months, three patients from the second schedule are still alive.

Median overall survival (mOS) for advanced pancreatic carcinoma patients in the first schedule was 6.8 months; one patient showed a complete response and is still alive 41 months (as of Jan 2009) after receiving trabedersen therapy. The current mOS for pancreatic carcinoma patients in the first cohort of five patients in the second schedule is 13.4 months (as of Feb 2009); one patient is still alive with stable disease 15.6 months (as of Feb 2009) after start of study treatment.

Need for new therapies in oncology
“Despite some big leaps forward in oncology therapy, many cancers remain difficult to treat with a very poor prognosis. New therapeutic approaches are desperately needed and trabedersen shows huge potential to treat a wide range of aggressive cancers. The results of the Phase I/II study announced show that trabedersen has a good safety and tolerability profile and potential survival benefits. Trabedersen could make a real difference to patients‘ lives,“ said Dr. Helmut Oettle, Coordinating Investigator, Campus Virchow-Klinikum, Charité Medical Faculty of the Humboldt University of Berlin.

Study design of Phase III SAPPHIRE trial
The SAPPHIRE study, in which the first patients with recurrent or refractory anaplastic astrocytoma have now been recruited, has a primary efficacy endpoint of survival rate at 24 months. Further efficacy endpoints include the overall survival and time to death. The 14-month progression rate is the surrogate endpoint for an interim analysis. Safety parameters will include adverse events, serious adverse events, electrocardiogram (ECG) parameters, neurological examination and vital signs. Patient quality of life is an additional important parameter of the study.

The design of the Phase III SAPPHIRE study is based on results from clinical Phase IIb study AP 12009-G004, a randomized and active-controlled dose-finding study. In this Phase IIb trial, 134 patients with HGG were randomized and trabedersen was administered intratumorally by convection-enhanced delivery. A survival benefit of 17.4 months was seen for patients receiving trabedersen vs. standard chemotherapy (patients suffering from recurrent or refractory anaplastic astrocytoma, WHO grade III). In recurrent or refractory anaplastic astrocytoma, twice as many patients (83.3%) treated with trabedersen 10 μM survived two years or more, compared to the control arm with standard chemotherapy (41.7%).

Role of TGF-β2 in tumor progression
Trabedersen is a first-in-class gene silencing antisense compound - a phosphorothioate oligodeoxynucleotide - designed to selectively downregulate the production of transforming growth factor-beta 2 (TGF-β2) at the translational level. TGF-β2 plays a pivotal role as a multimodal cytokine by regulating key mechanisms of tumor progression. Immunosuppression, invasion and metastasis, proliferation and angiogenesis are simultaneously promoted by TGF-β2 in a variety of malignant tumors. Trabedersen is a targeted multimodal therapy.

Targeted therapies drive market growth
Unlike non-specific therapies, e.g. chemotherapy or radiotherapy, targeted therapies act specifically at the molecular roots of the disease. Commanding up to 80% of the growing oncology market, the targeted therapies like trabedersen substantially drive the growth of the pharmaceutical market (Source: IMS Health). A successful marketing authorization would make trabedersen the first TGF-beta targeting drug for the treatment of cancer.

Antisense Pharma: committed to developing new therapies that make
a real difference to patients
“This additional data relating to the use of trabedersen in a wide range of difficult-to-treat cancers shows the potential broad applicability of our lead compound. This news, combined with successful initiation and patient enrollment in the Phase III SAPPHIRE study, means that the development of trabedersen is accelerating. We hope to build on this success and that trabedersen will ultimately be able to deliver clinical benefits to a broad range of patients,“ commented Dr. Karl-Hermann Schlingensiepen, Chief Executive Officer of Antisense Pharma.


Additional information

For more information on the clinical Phase I/II study in advanced pancreatic carcinoma or malignant melanoma please visit the website (in German). For more information on the SAPPHIRE trial in recurrent or refractory anaplastic astrocytoma please visit the website

This news announcement is based on two poster presentations at ASCO 2009. Further details on the poster presentations are given below:

POSTER 1 (abstract #2037)
Title: Randomized, Active-Controlled Phase IIb Study with trabedersen (AP 12009) in Recurrent or Refractory High-Grade Glioma: Basis for the Phase III SAPPHIRE study Design
Presented by: Prof. Dr. Ulrich Bogdahn
Date: Sunday, May 31st, 2009, 8:00 AM -12:00 AM
Location: Level 2, West Hall C

POSTER 2 (abstract #4619)
Title: Interim Results of the Phase I/II Study of trabedersen (AP 12009) in Patients with Pancreatic Carcinoma, Malignant Melanoma or Colorectoral Carcinoma
Presented by: PD Dr. Helmut Oettle
Date: Sunday, May 31st, 2009, 8:00 AM - 12:00 AM
Location: Level 2, West Hall C

About Antisense Pharma GmbH
Antisense Pharma is a biopharmaceutical company located in Regensburg, Germany. The company focuses on targeted gene-silencing therapies for malignant tumors and is dedicated to discovering and developing drugs based on antisense technology for worldwide commercialization. The medications specifically block the synthesis of key cancer proteins. Antisense Pharma has currently clinical trials running that involve patients with brain tumors, advanced pancreatic carcinoma, malignant melanoma and colorectal carcinoma. Therapies for other indications are under preclinical development. The company has been honored with the Bavarian Innovation Award and the German Founder‘s Award.

Antisense Pharma GmbH

Dr. Alexis Katechakis
Public Relations

Josef-Engert-Straße 9
93053 Regensburg

Telefon: +49 (0) 941 920 13 - 0
Telefax: +49 (0) 941 920 13 - 29


Posted: June 2009