Public Release: 

New substance overcomes treatment-restistance in leukemia

Successful tests in cultures and mouse models for Philadelphia chromosome positive leukemia through German-Russian collaboration

Goethe University Frankfurt

This news release is available in German.

FRANKFURT The chances of patients with Philadelphia chromosome-positive leukaemia (Ph+) being cured has greatly increased in recent years. Nevertheless, a high percentage of patients have developed resistance to available medication. But now, haematologists from Frankfurt, working with a Russian pharmaceutical company, have developed a new active substance that effectively combats the most aggressive forms of Philadelphia chromosome-positive leukaemia, both in vitro and in vivo. They have reported this in the current edition of the renowned specialist journal 'Leukaemia'.

Patients with the Philadelphia chromosome develop chronic myelogenous leukaemia (CML) or acute lymphatic leukaemia (Ph+ ALL). These are the first types of leukaemia that are able to be treated due to the development of targeted molecular therapy. Selective kinase inhibitor active substances act directly on the cancer-inducing gene BCR/ABL. However, after a while, the treatment becomes ineffective for many patients - either due to BCR/ABL mutations or due to other mechanisms that are as yet unknown. At present, there is only one substance, Ponatinib, which is able to overcome nearly all clinical resistance. Unfortunately, Ponatinib can only be used with extreme caution due to some of its life-threatening side-effects.

Moscow-based company Fusion Pharma has developed an innovative kinase inhibitor, PF-114 with the aim of having the same effect on Ph+ leukaemia as Ponatinib, but with reduced side-effects. In the current edition of 'Leukaemia', the team led by Dr. Afsar Mian, Professor Oliver Ottmann and lecturer Dr. Martin Ruthardt from the Haematology Department of Medical Clinic II, have reported that PF-114 is as effective as Ponatinib against resistant Ph+ leukaemia.

"These results provide the basis for the administration of PF-114 in treatment-resistant patients with Ph+ leukaemia. The favourable efficacy and good side effect profile now need to be further tested on patients in clinical phase I studies," explained Dr. Ruthardt. "PF-114 would not have reached this level of development without our colleagues in Frankfurt. On the basis of this data, in the first half of 2015, we will be able to start international phase I studies," explains Dr. Ghermes Chilov, CEO of Fusion Pharma, the company that financed the project.

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Publication:

Mian et al.: PF-114, a potent and selective inhibitor of native and mutated BCR/ABL is active against Philadelphia chromosome- positive (Ph+) leukaemias harbouring the T315I mutation, in Leukemia, 14. November 2014, doi: 10.1038/leu.2014.326.

Information: Lecturer Dr. Martin Ruthardt, Haematology/Medical Clinic II, University Clinic, Tel. ++49(0)69 6301-5338, ruthardt@em.uni-frankfurt.de.

The Goethe University is an institution with particularly strong research capabilities based in the European financial metropolis of Frankfurt. It celebrates its 100th year of existence in 2014. The university was founded in 1914 through private means from liberally-orientated citizens of Frankfurt and has devoted itself to fulfilling its motto "Science for the Society" in its research and teaching activity right up to the present day. Many of the founding donors were of Jewish origin. During the last 100 years, the pioneering services offered by the Goethe University have impacted the fields of social, societal and economic sciences, chemistry, quantum physics, neurological research and labour law. On January 1st, 2008, it achieved an exceptional degree of independence as it returned to its historical roots as a privately funded university. Today it is one of the ten universities that are most successful in obtaining external research funding and one of the three largest universities in Germany with centres of excellence in medicine, life sciences and humanities.

Publisher: The president of the Goethe University Frankfurt am Main. Editorial department: Dr. Anke Sauter, Science editor, Department Marketing and Communications, Grüneburgplatz 1, 60629 Frankfurt am Main, Phone: ++49(0)69 798-12498.

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