Merck KGaA drug blasts aggressive brain tumours

By Mike Nagle

- Last updated on GMT

Related tags: Merck kgaa, Brain tumor

A new drug from Merck KGaA could be the first in a new type of
anticancer therapy that works by starving the tumour of its blood

The company has presented 'encouraging' results from two Phase I/II clinical trials at this week's 43rd American Society of Clinical Oncology (ASCO) conference in Chicago, US. Cilengitide is a peptide-like drug, which could potentially be the first so-called 'integrin inhibitor' on the market. The molecule is currently being tested in Phase I and Phase II clinical trials against the most aggressive form of brain cancer - glioblastoma. With current therapies, the average patient survival time is between 12 and 15 months and glioblastomas have a near 80 per cent mortality rate within two years, irrespective of treatment. Novel therapies are therefore desperately needed. ·Cilengitide has been granted orphan designation in both the European Union and the United States for the treatment of glioma and malignant glioma, respectively. Integrins are a family of protein receptors found in membranes, with many cells having many different types on their surface. They are used to regulate cell signalling and control certain cell functions such as growth, differentiation and motility. The proteins also mediate interactions between cells and the extracellular matrix - any part of a tissue outside of cells. When a tumour grows new blood vessels, they sprout into the extracellular matrix. This process is only possible through the complex interaction of the vessels' endothelial cells with the glycoproteins in the matrix. Therefore, integrin mediators are crucial to the process of tumour angiogenesis. Cilengitide, a cyclic Arg-Gly Glu (RGD) pentapeptide, targets two specific integrins, which are thought to be particularly important for angiogenesis. The targets are integrin alpha5,beta3 and integrin alpha5,beta5 - so called because each protein is formed from two distinct subunits. In the first trial, 52 patients were treated with cilengitide in combination with radiotherapy and Schering-Plough's Temodar (temozolomide). After six months, 69 per cent of patients' tumours had not progressed and the average time of progression free survival (PFS) was 8.1 months. Especially encouraging were the results for a subset of patients who has the methylated MGMT gene in the tumour tissue - 91 per cent PFS and the average time has not yet been reached, according to Merck KGaA. The results compare favourably with a historical control trial jointly conducted by the European Organisation for Research and Treatment of Cancer (EORTC) and the National Cancer Institute of Canada (NCIC). In this Phase III trial, which examined the effects of Temodar plus radiotherapy, the average PFS was 6.9 months, rising to 10.3 months in the same patient subset. After six months, the percentage of patients whose tumours had not grown was 54 per cent and 69 per cent for the subset. "We are excited by these findings. They demonstrate the potential of cilengitide to make a real difference to the outcome of patients with this aggressive type of brain cancer, where currently available treatment options are limited and prognosis is poor,"​ said Dr Roger Stupp of the University of Lausanne Hospital in Switzerland, who was lead investigator on the trial. The results for a second trial, looking at cilengitide as a monotherapy, were also presented at the conference. However, the data was disappointing - the company had set a target of 25 per cent of patients being progression free at six months. The actual rate was 16 and 10 per cent at six and 12 months, however. Dr Wolfgang Wein, head of oncology at Merck Serono - a division of Merck KgaA said the company is now planning to move onto a Phase III trial to examine the effects of cilengitide in a larger group of patients.

Related topics: Preclinical Research

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