EntreMed, Inc. announced recent developments in its program for ENMD-2076, an Aurora A/angiogenic kinase inhibitor. These developments include the presentation of initial results for a Phase 1 study in patients with refractory solid tumors, as well as pre-clinical data showing significant potential for the use of ENMD-2076 in combination with platinum-based chemotherapy in breast cancer. In addition, EntreMed has received an Orphan Drug Designation from the FDA for the treatment of multiple myeloma using ENMD-2076. To further enhance its clinical development efforts for the drug candidate, a No Objection Letter was received by EntreMed from Health Canada permitting ENMD-2076 to be used in clinical trials within Canada.
Results from the ongoing Phase 1 study in patients with refractory solid tumors demonstrated that ENMD-2076 administered orally in 28-day cycles was well tolerated. Data show preliminary evidence of anti-tumor activity as determined by reduction in tumor markers in ovarian and colorectal cancer patients. Dose escalation continues to determine the primary endpoints of the study, safety, pharmacokinetics, and a Phase 2 dose.
During the symposium, EntreMed’s Senior Director, Translational Research, William E. Fogler, Ph.D., presented results from a pre-clinical evaluation of ENMD-2076 in combination with cisplatin in a multi-drug resistant, triple-negative human breast carcinoma model. Triple-negative breast cancer is a specific subtype of breast cancer that does not express estrogen receptor, progesterone receptor, or Her2 genes. This subtype is more aggressive and less responsive to standard treatment and is also associated with poorer patient prognosis. Data shows the combination is well tolerated when using a maximally tolerated dose of cisplatin and a range of ENMD-2076 doses. Studies demonstrate a substantial dose-dependent anti-tumor combination effect as assessed by tumor regression. The enhanced anti-tumor activity observed with the combination of ENMD-2076 and cisplatin, over either agent alone, is correlated to biomarkers of angiogenesis, proliferation and apoptosis. These results provide a rationale for the clinical evaluation of ENMD-2076 in tumors responsive to platinum compounds, and particularly in triple-negative breast disease refractory to standard of care agents.
To further expand the clinical development of ENMD-2076, EntreMed has received a No Objection Letter (NOL) from the Therapeutic Products Directorate of Health Canada on its Clinical Trial Application to conduct a clinical study in Canada for ENMD-2076 in patients with hematological malignancies. A Canadian Clinical Trial Application (CTA) is similar to a United States Investigational New Drug (IND) application. The Company plans to commence a Phase 1 study in patients with relapsed or refractory leukemias in Canada later this year.
In addition, the U.S. Food and Drug Administration (FDA) granted orphan drug designation for ENMD-2076 for the treatment of multiple myeloma. The FDA accepted the Company’s application based on review of data from preclinical studies. A Phase 1 study with ENMD-2076 in multiple myeloma is currently underway. Orphan drug is a designation by the Food and Drug Administration indicating a therapy developed to treat diseases that affect fewer than 200,000 persons in the United States. Sponsors of drugs granted orphan designation qualify for tax credit and marketing exclusivity incentives of the Orphan Drug Act.
Release Date: February 9, 2009
Filed Under: Drug Discovery