Health Canada approves Antisense Pharma's clinical Phase III study SAPPHIRE
in aggressive brain tumors

    
    Study to examine trabedersen vs. current standard chemotherapy in
    patients with recurrent or refractory anaplastic astrocytoma
    

REGENSBURG, Germany, Oct. 19 /CNW/ - The biopharmaceutical company Antisense Pharma GmbH has announced today that it has received the approval by Health Canada for its pivotal Phase III clinical trial SAPPHIRE in patients with recurrent or refractory anaplastic astrocytoma.

The SAPPHIRE study is a randomized, active-controlled, clinical trial designed to confirm the efficacy and safety of the investigational drug trabedersen (AP 12009), observed in previous clinical studies. Trabedersen is being investigated as monotherapy compared to current standard therapy with temozolomide (alternatively BCNU (carmustine)). The results of a previous randomized, active-controlled Phase IIb study show that the novel, targeted therapy holds significant promise. Currently recruiting study centers will be published on www.anticancer.de.

International Phase III study design

The SAPPHIRE study is being carried out in Europe, North, Middle and South America along with Asia. Up to 100 hospital centers will participate. The Phase III study is designed as a randomized, active-controlled, open-label clinical trial with two treatment arms: Trabedersen in a dose of 10 umol will be compared to current standard therapy with temozolomide (alternatively BCNU (carmustine)). Clinical centers conducting the SAPPHIRE study aim to enroll a total of approximately 130 adult patients with recurrent or refractory anaplastic astrocytoma. Trabedersen will be administered intratumorally via one single catheter using convection-enhanced delivery (CED) on an outpatient treatment basis. The treatment period lasts up to 6 months consisting of 7-day cycles every other week.

Study objectives

The primary efficacy endpoint is the survival rate at 24 months. Further efficacy endpoints include 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, ECG parameters, neurological examination and vital signs. Also the patient's quality of life is an important parameter of the study.

Great need for new approaches in cancer therapy

"The diagnosis of recurrent or refractory anaplastic astrocytoma is devastating since the therapeutic possibilities available to treat such patients are inadequate. The life expectancy of such patients is unfortunately very limited. Hospitals worldwide are committed to improve this situation in the framework of the SAPPHIRE study. The results of the previous studies show that this new, targeted therapy holds significant promise", remarked Dr. Rolando Del Maestro, Director of Brain Tumor Research at the Montreal Neurological Institute and Hospital, McGill University. Dr. Del Maestro is the World Coordinating Investigator of the SAPPHIRE study.

Targeted therapies drive market growth

Trabedersen is a first-in-class targeted therapy. This novel compound acts multimodally via inhibition of transforming growth factor-beta 2 (TGF-beta-2). Unlike non-specific therapies, e.g. chemotherapy or radiotherapy, targeted therapies act much more specifically at the molecular basis of the disease. Commanding up to 80% of the growing oncology market, the targeted therapies like trabedersen are substantially driving the growth of the pharmaceutical market.(1) A successful marketing authorization would make trabedersen the first TGF-beta targeting drug for the treatment of cancer.

Combating cancer at its roots

"We have taken trabedersen all the way from drug discovery to the pivotal Phase III clinical trial. The approval of the SAPPHIRE study by Health Canada is an important step in our efforts to make trabedersen available to those who need it as quickly as possible. Trabedersen is also in Phase I/II clinical development for advanced pancreatic carcinoma, malignant melanoma and colorectal carcinoma. With its unique mode of action, we believe that trabedersen has the potential to lead to a paradigm shift towards tackling malignant tumors at their roots while providing a longer life and a better quality of life for patients," commented Dr Karl-Hermann Schlingensiepen, Chief Executive Officer of Antisense Pharma.

For more information on the SAPPHIRE trial please visit the website www.anticancer.de.

Additional information

Original title Phase III SAPPHIRE study

Efficacy and Safety of AP 12009 in Adult Patients with Recurrent or Refractory Anaplastic Astrocytoma (WHO grade III) as Compared to Standard Treatment with Temozolomide or BCNU: A Randomized, Actively Controlled, Open-label Clinical Phase III Study.

Principal Investigator: Dr. Rolando Del Maestro, MD, PhD, Director Brain Tumour Research Centre, Montreal Neurological Institute and Hospital, Canada.

How trabedersen works

Trabedersen is a first-in-class, targeted, antisense compound (a phosphorothioate oligodeoxynucleotide) designed to selectively downregulate the production of a protein known as transforming growth factor-beta 2 (TGF-beta-2) at the translational level.(2),(3) Various aggressive tumors such as high-grade gliomas, advanced pancreatic cancer, malignant melanoma and advanced colorectal cancer cells produce an excessive amount of TGF-beta-2, which plays a critical role in tumor progression (proliferation, angiogenesis and metastasis) and acts as a shield that protects the tumor from the body's immune system.(2),(3),(4) By inhibiting TGF-beta-2, trabedersen has multiple antitumoral effects: it hinders tumor progression, angiogenesis and metastasis.(2),(5) In addition, trabedersen restores the body's immune system, by breaking down the protective shield so that the immune system can recognize and destroy the tumor cells.

Results of the Phase IIb study with trabedersen

The completed clinical Phase IIb study AP 12009-G004 was an open-label, randomized, active-controlled, parallel-group dose-finding study to evaluate the efficacy and safety of two doses of trabedersen (AP 12009) in adult patients with recurrent or refractory high-grade glioma. At 29 international clinical centers, 134 evaluable patients (39 with recurrent or refractory anaplastic astrocytoma, AA, WHO grade III and 95 with recurrent or refractory glioblastoma, GBM, WHO grade IV) were randomized to three arms: 10 umol trabedersen, 80 umol trabedersen or standard chemotherapy (temozolomide or PCV) as active control. Analysis of the core phase revealed long-lasting tumor responses and life extension in AA and GBM patients, by far exceeding the active treatment period with trabedersen. For recurrent or refractory anaplastic astrocytoma patients, median survival times in the 10 umol trabedersen group were 39.1 months compared to 21.7 months in the standard chemotherapy control arm, translating to a survival benefit of 17.4 months for patients receiving the antisense treatment over standard chemotherapy. 83.3% of the patients with recurrent anaplastic astrocytoma who received 10 umol trabedersen survived two years or more, whereas only 41.7% survived two years in the control arm with standard chemotherapy. Both efficacy and safety results have demonstrated, that the 10 umol concentration of trabedersen is the recommended dose for future clinical development in high-grade glioma.

High-Grade Glioma

Anaplastic astrocytoma (AA) and glioblastoma multiforma (GBM) are the two most common forms of primary brain tumors and are diseases with high unmet medical need. Adults as well as children may be affected, although the peak age is 45-65 years. Current therapies comprise surgery, radiation and/or chemotherapy. Despite recent advances, the prognosis for these patients is still poor, with a high proportion dying within two years after initial diagnosis. Antisense Pharma is the sponsor of the SAPPHIRE clinical Phase III study, investigating the efficacy and safety of trabedersen (AP 12009) in adult patients with recurrent or refractory anaplastic astrocytoma. A further clinical trial with trabedersen to treat glioblastoma patients is in preparation.

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 and was awarded one of the 100 most innovative medium-sized companies in Germany in 2009.

    
    References

    1. IMS Health
    2. Schlingensiepen KH et al. (2006) Cytokine Growth Factor
       Rev 17(1-2):129-139
    3. Tsamandas, AC, Kardamakis, D et al. (2004) The potential role of
       TGFbeta1, TGFbeta2 and TGFbeta3 protein expression in colorectal
       carcinomas. Correlation with classic histopathologic factors and
       patient survival. Strahlenther Onkol 180(4):201-8
    4. Kouvidou, C, Latoufis, C et al. (2006) Expression of Smad4 and
       TGF-beta2 in colorectal carcinoma. Anticancer Res 26(4B):2901-7
    5. Schlingensiepen R et al. (2005) Oligonucleotides 15(2):94-104
    

SOURCE ANTISENSE PHARMA GMBH

For further information: For further information: Antisense Pharma GmbH, Dr. Alexis Katechakis, Public Relations; Josef-Engert-Str. 9, D-93053 Regensburg, Phone: +49-941-92013-0, Fax: -29, E-mail: pr@antisense-pharma.com, Web: www.antisense-pharma.com; Liv Communications, Sandra Vlaar Ingram, Office: (905) 309-4115, Mobile: (905) 741-7640, E-Mail: sandra@livcomm.com

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