Phase I & II with MESUPRON®

MESUPRON® is a serine protease inhibitor targeting the uPA (urokinase Plasminogen Activator) system. Therefore MESUPRON® was moved into clinical development targeting tumour indications where long-term chronic treatment is necessary.
The studies were partly supported by a USD 5.0 million award from the Department of Defence’s Breast Cancer Research Program.

As MESUPRON® was shown to be safe and well-tolerated and demonstrated good inhibition of tumour growth and metastasis in pre-clinical studies, MESUPRON® was moved into clinical development.

MESUPRON® has successfully completed two European Phase I studies in healthy volunteers. In a “first-into-man” Phase I single-dose study, MESUPRON® was safe and well tolerated at all dose levels tested and, in addition, showed good oral bioavailability, i.e. absorption by the gut, and efficient conversion to the active drug WX-UK1 in the body. A placebo controlled, double-blind study tested safety, tolerability, and pharmacokinetics of multiple rising doses of MESUPRON® in healthy volunteers. The study has been successfully completed.

A European Phase Ib in patients with head and neck tumours has shown in 2007 that once daily oral doses of MESUPRON® delivers adequate concentrations of active WX-UK1 in tumour tissues in patients.

Status

Currently, MESUPRON® is being studied in two Phase II studies in patients with pancreatic cancer or breast cancer.

Pancreatic cancer
Recruitment of 95 patients with locally advanced, inoperable, non-metastatic pancreatic cancer was completed in July 2008. The randomised, open label, three-arm Phase II trial investigates the anti-metastatic effect of MESUPRON® in combination with the chemotherapeutic agent Gemcitabine (Gemzar®, Eli Lilly and Company, Indianapolis, IN, USA). Patients were administered either Gemcitabine alone or in combination with a daily oral dose of 200 mg or 400 mg MESUPRON® respectively until progression. The therapy has proven to be safe and well tolerated. The trial examines different parameters, including progression-free survival and the time it takes for the first metastases to occur.

Positive final data of the study was presented in June 2010 at ASCO (American Society of Clinical Oncology). Gemcitabine alone demonstrated a tumour response rate of 15.4%. Co-administration of 200 mg MESUPRON® led to an increase to 21.4% and to 35.5% with 400 mg MESUPRON®.

Progression free survival (PFS) improved by 66%. In the group receiving Gemcitabine alone 16.2% of patients did not progress at 12 months as determined by computer tomography. Co-administration of 200 mg MESUPRON® improved PFS to 22.5% and to 26.9% with 400 mg MESUPRON®.

One year survival increased by 49%. With Gemcitabine alone it was 33.9%. This increased to 40.7% with 200 mg MESUPRON® and to 50.6% with 400 mg MESUPRON®. The median survival of the patients improved by 26% from 9.9 months with Gemcitabine to 12.5 months in combination with 400 mg MESUPRON®.

Further information can be found on the poster that was presented at the ASCO 2010.

Breast cancer
In January 2008, WILEX also obtained approval to commence a second Phase II trial with MESUPRON® in patients with metastatic, HER2 receptor negative breast cancer. This randomised double-blind Phase II trial involves 114 patients. It is designed to examine the efficacy of combination therapy of MESUPRON® and Capecitabine (Xeloda®, Hoffmann-La Roche AG, Basel, Switzerland) compared to monotherapy with Capecitabine. The trial’s primary endpoint is progression-free survival, i. e. the length of time patients survive without further development of the disease. The patients receive the drugs in first-line treatment, i. e. the first treatment following a relapse. Patient recruitment for this trial began in August 2008. 84 patients were recruited up to the end of June 2010 in 20 study sites.

Further information can be found on the poster that was presented at the ASCO 2010.