Wednesday, 2 February 2011

Clinical studies in South Korea and Taiwan in malignant brain tumours

The biopharmaceutical company Antisense Pharma today announced that the South Korean health agency KFDA as well as the Taiwanese health agency TFDA have granted their approvals for the implementation of clinical studies using the anti-cancer drug trabedersen for patients with high-grade brain tumours.

Trabedersen is a gene-silencing substance inhibiting the tumor factor Transforming Growth Factor beta 2 (TGF-β2) at its translational level. The efficacy and tolerability of trabedersen for high-grade glioma has already been demonstrated during a randomized and actively controlled Phase IIb study1. The substance is currently also in clinical development for indications such as advanced pancreas carcinoma, malignant melanoma and colorectal carcinoma. The involvement of Southeast Asian countries for clinical testing of trabedersen is part of Antisense Pharma’s strategic development programme for the global marketing of this compound. Including South Korea and Taiwan, a total of 13 countries are now participating in the international pivotal study.

The randomized and actively controlled Phase III study SAPPHIRE is scheduled to begin at selected medical centres in South Korea and Taiwan during the first quarter of 2011. The medical demand for therapies against high-grade brain tumours remains to be high: according to the World Health Organization (WHO), Southeast Asia annually has more than 13,000 incident cases of central nervous system tumors, with a mortality rate of more than 77%2.

“Our pivotal Phase III study not only meets the enormous interest in trabedersen of South Korean and Taiwanese physicians, who – just as their colleagues from all over the world – have so far no satisfactory medical treatment to provide to their critically ill patients suffering from malignant brain tumours“, explains Dr Karl-Hermann Schlingensiepen, Chief Executive Officer of Antisense Pharma. “The global involvement of neurosurgeons and neurooncologists for the clinical development of trabedersen also allows us to introduce them to our completely new therapy concept at an early stage. This means that by the time trabedersen will be launched, these doctors will be familiar with the concept and can leverage their clinical practice experience.”

“The excellent exchange with the regulatory authorities in South Korea and Taiwan has led to a prompt granting of approvals, thus confirming the professional work of our team and Antisense Pharma’s expertise in clinical drug development“, comments Dr Hubert Heinrichs, Chief Medical Officer of Antisense Pharma. “Key factors for the decision taken by KFDA and TFDA have surely been the very encouraging results of previous clinical studies which confirm the safety, tolerability and efficacy of trabedersen.”

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 tumour progression. Immunosuppression, invasion and metastasis, proliferation and angiogenesis are simultaneously promoted by TGF-β2 in a variety of malignant tumors. Therefore Trabedersen is a targeted multimodal therapy and one of the very promising immunotherapeutic approaches in the oncological field. Besides in high grade glioma, trabedersen is also being investigated in other aggressive cancers which over-express TGF-β2: Trabedersen is being systemically administered intravenously (i.v.) in adult patients with advanced pancreatic carcinoma, malignant melanoma, or advanced colorectal carcinoma in an ongoing Phase I/II study.

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 pivotal international SAPPHIRE clinical Phase III study, investigating the efficacy and safety of trabedersen (AP 12009) in adult patients.

1. Bogdahn U et al. Targeted therapy for high-grade glioma with the TGF-β2 inhibitor trabedersen: results of a randomized and controlled phase IIb study. Neuro Oncol, 2010, doi:10.1093/neuonc/noq142 <>
2 .Globocan 2008, //

Antisense Pharma GmbH