MESUPRON® – Oral uPA Inhibitor
MESUPRON® (INN: upamostat) is an oral uPA/serine protease inhibitor, which has been developed by Heidelberg Pharma until Phase II. It is designed to block the activity of tumor-relevant serine proteases such as uPA, plasmin and thrombin to prevent tumor growth and metastasis.
In 2014, the development and commercialization rights for MESUPRON® were out-licensed to Link Health Co., Guangzhou, China (Link Health) for China, Hong Kong, Taiwan and Macao, and RedHill Biopharma Ltd., Tel Aviv, Israel (RedHill) for the rest of the world.
In early January 2016, Link Health submitted an investigational new drug (IND) application to the China Food and Drug Administration (CFDA) for a Phase I dose-escalation study with MESUPRON®. The IND is expected to be granted in 2017. Following this trial, which is expected to confirm the optimal biological dose, further Phase II trials in cancer patients are planned.
The partner RedHill conducted non-clinical trials in 2016 and analyzed certain earlier clinical data in order to define the molecular markers and the patient groups for future trials more precisely. RedHill has entered into a research alliance with the Institute of Molecular Biology and Genetics of Aarhus University in Denmark to identify further high-affinity molecular target proteins for MESUPRON®. This should help to optimize patient selection for the planned clinical trials. RedHill has announced plans to begin a Phase II clinical trial in 2018.
REDECTANE® – Diagnostic Antibody
REDECTANE® (INN: 124I-Girentuximab) is a radiolabeled form of the antibody Girentuximab, which binds to the antigen CAIX (carbonic anhydrase IX) on clear cell renal cell carcinoma. Accumulation of this antibody in tumor tissue can be visualized by positron emission tomography scans (PET). Additional information provided by computer tomography (CT) can be used to localize the accumulation of the antibody. This could fundamentally change therapy planning for renal cancer patients and avoid potentially unnecessary surgery. REDECTANE® may also prove suitable for monitoring response to treatment and for diagnosing other kinds of tumors.
The Phase III REDECT trial completed in 2010 showed that REDECTANE® can differentiate between clear cell and non-clear cell renal cell cancer and that PET/CT with REDECTANE® was clearly superior to CT. In September 2012, an agreement was reached with the FDA to conduct a confirmatory diagnostic performance study. Heidelberg Pharma drew up the development strategy and trial design for a confirmatory Phase III trial (REDECT 2), for which it received a special protocol assessment (SPA) from the FDA in 2013.
In January 2017, an exclusive license agreement for the development and commercialization of the imaging agent REDECTANE® was signed with the Australian company Telix Pharmaceuticals Limited, Melbourne, Australia (Telix). Initially, Telix will invest in an improved manufacturing process for the antibody. Telix then will have to conduct a further confirmatory diagnostic performance (Phase III) study. All further development and marketing activities for this product candidate will be carried out by this partner. Telix also plans to develop a therapeutic radioimmunoconjugate program based on the Lutetium-177-labeled Girentuximab antibody.
RENCAREX® – Therapeutic Antibody
RENCAREX® (INN: Girentuximab) is a chimeric monoclonal antibody made from human and murine genetic sequences that binds to the tumor-specific antigen CAIX. This antigen is expressed in several types of cancer but is generally not present in healthy tissue. The fact that the antibody binds to the antigen makes the tumor visible to the endogenous immune system such that natural killer cells can bind to destroy the tumor. CAIX is also present in renal, colon and head and neck cancer.
Renal cell carcinoma (RCC) is the most common type of kidney cancer and accounts for more than 90% of malignant kidney tumors. Two-thirds of RCC patients show no evidence of metastases at the time of first diagnosis but have a high risk of relapse within a few years after surgery. RENCAREX® is designed to prevent relapsing tumor cells or metastases (adjuvant therapy).
In October 2012, Heidelberg Pharma announced results of the Phase III ARISER trial with RENCAREX® (INN: Girentuximab) to treat clear cell renal cell carcinoma (ccRCC). The trial did not meet its primary endpoint. The analysis showed no improvement in median DFS (approximately 72 months) following RENCAREX® treatment compared with placebo. RENCAREX® was safe and well tolerated. The Independent Data Monitoring Committee (IDMC) has recommended terminating the Phase III ARISER trial.
Further development of this immunotherapy at Heidelberg Pharma will not be conducted. It may be possible to further develop RENCAREX® with a partner.