ANTISENSE PHARMA GmbH Receives FDA Orphan Drug Designation for Trabedersen to Treat Malignant Melanoma

Regensburg, Germany, July 24, 2012 / B3C newswire / - The biopharmaceutical company Antisense Pharma GmbH announces that the US Food and Drug Administration (FDA) has granted Orphan Drug designation for its investigational oncology antisense compound trabedersen to treat malignant melanoma.

Previously, trabedersen has received Orphan Drug designation by the European EMA and the US FDA in high-grade glioma (malignant brain tumor) in 2002 and in advanced pancreatic cancer in 2009.

Dr. Philippe Calais, Chief Executive Officer of Antisense Pharma comments: “We are delighted that with this most recent designation by the FDA, Trabedersen has now orphan status for three different cancer indications. With the orphan status and the associated marketing protection, we have achieved a core milestone for the long-term commercial success of our oncology lead compound trabedersen.”

Dr. Hubert Heinrichs, Chief Medical Officer of Antisense Pharma elaborates: “Malignant melanoma is a very aggressive disease with a high need for innovative, effective and well-tolerated treatment options. We are confident that traberdersen will provide new hope to patients that suffer from malignant melanoma. Recently published results of our Phase I/II Study1 with traberdersen demonstrated excellent tolerability and initial encouraging survival data in patients with advanced tumors. We are currently evaluating further clinical development of traberdersen in malignant melanoma, preferably together with a potential partner.”


Malignant melanoma remains the most lethal skin cancer

Although melanoma accounts for only approximately 4% of all skin cancers it is responsible for more than 73% of skin cancer deaths.2 Once melanoma has metastasized to the lymph nodes (Stage III), the 5-year survival rate following surgical removal is only 20 to 50%. While treatment of melanoma stage I and II is mainly based on surgical removal of the skin lesion, treatment of stage III and IV (metastatic spread to other organ systems) additionally includes chemotherapy, target therapy against BRAF V600E mutation or immunotherapy.

Orphan drug designation secures exclusive market rights following product approval

Orphan Drug designation is designed to encourage pharmaceutical companies to develop drugs for life-threatening or chronically debilitating diseases that affect a relatively small patient population and for which there is currently no satisfactory treatment option available. It provides advantages to the company - such as complementary scientific advice from the regulatory authorities as well as the lowering or exemption of approval fees. Most importantly, it offers exclusive marketing rights for seven years in the US and 10 years in the EU following product approval.

Targeting transforming growth factor beta 2 – a promising immunotherapeutic approach

The antisense molecule trabedersen targets mRNA encoding the tumor factor transforming growth factor beta 2 (TGF-ß2) – a cytokine with an important role in the progression of malignant melanoma and other aggressive cancers. TGF-ß2 has been shown, inter alia, to stimulate metastasis and suppresses the immune system and thereby protects the tumor from being attacked by the endogenous immune cells.3

While TGF-ß2 cannot be detected in melanocytes of normal skin, TGF-ß2 levels clearly increase in tumor cells during tumor progression and are correlated with the degree of invasion by malignant cells in healthy tissue. The highest levels of TGF-ß2 are found in tissue of metastatic malignant melanoma Stage III and IV. The multiple key roles of TGF-ß2 in tumor progression make it an attractive drug target for a multimodal anti-tumor approach in the treatment of malignant melanoma and other advanced tumors. As far as the company is aware, trabedersen is one of the most advanced TGF-ß2 inhibitor drugs in clinical development, worldwide.

Trabedersen in malignant melanoma – final results from a Phase I/II study1

At the American Society of Clinical Oncology (ASCO), June 2012, Antisense Pharma presented final results of a clinical Phase I/II study of trabedersen. The compound was applied as systemic intravenous monotherapy in pre-treated patients with advanced malignant melanoma (MM, n=19), pancreatic cancer (PanCa, n=37), and colorectal cancer (CRC, n=5).

The primary objective of this Phase I/II study in 61 patients, AJCC stage III/IV, was to determine the maximum tolerated dose (MTD) and the dose limiting toxicity (DLT) of trabedersen. Secondary objectives included safety and tolerability, pharmacokinetic profile and anti-tumor activity.


The MTD within the 7 days on traberdersen/7 days off trabedersen schedule was established at 160 mg/m2/d. In the schedule 4 days on traberdersen/10 days off traberdersen dose-escalation was stopped before reaching MTD. The study demonstrated trabedersen’s optimal treatment schedule as being 4 days on traberdersen/10 days off traberdersen with a well-tolerated dose of 140 mg/m2/d.

The study demonstrated that trabedersen is safe and very well tolerated. DLTs were maculopapular rash (n=1, non-serious), moderate, reversible thrombocytopenia (n=2, non-serious), and gastrointestinal hemorrhage (n=1, serious, reversible). Furthermore one event of fever was considered as serious adverse event (SAE) related to trabedersen. Overall only thrombocytopenia (non-serious, reversible, not requiring treatment) was classified as an expected adverse reaction of trabedersen so far.

The study results with regards to efficacy of traberdersen are promising. The extensively pre-treated 19 metastatic melanoma patients (stage IV) obtained a median overall survival of 11.4 months during treatment with traberdersen. It is noteworthy that one patient with malignant melanoma stage IV was still alive 26 months after the completion of treatment with trabedersen (status as of August 2011).

Trabedersen obtained Orphan Drug designation in the USA for malignant melanoma stage IIb to IV. The further clinical development of trabedersen in advanced metastatic melanoma is currently being evaluated.

About Antisense Pharma

Antisense Pharma GmbH is a biopharmaceutical company located in Regensburg, Germany. The company focuses on the development of oncological drugs based on antisense technology for yet incurable cancer diseases. It pursues an immunotherapeutic strategy with a potentially long-lasting effect. As targeted therapies, antisense investigational drugs specifically block the synthesis of key cancer proteins which cause the development and the aggressive progression of cancer diseases. The company has been honored with the German Founder‘s Award and the Bavarian Innovation Award and twice received the TOP 100 Innovation.

For further information please contact:

Antisense Pharma GmbH

Dr. Andrea Kottke

Head of Marketing & Public Relations

T. +49 (0)941 92013 126

MC Services

Mareike Mohr

T. +49 (0) 89 21 02 28 40


1. Oettle H et al. (2012) ASCO American Society of Clinical Oncology #4034, abstract and poster presentation

2. Medscape Reference: Swetter SM. Cutaneous Melanoma – Epidemiology (updated April 2011)

3. Roberts AB Wakefield LM (2003). Proc Natl Acad Sci USA 100(15):8621. The two faces of transforming growth factor beta in carcinogenesis

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