Berubicin’s unique properties allows extension of the well established anthracycline class into the treatment of deadly brain tumors

Berubicin – Novel Anthracycline for Brain Cancers

Berubicin hydrochloride (formerly known as RTA 744) is a novel anthracycline in Phase 2 clinical studies. This agent has been well tolerated and has demonstrated excellent activity against brain tumors. It is in Phase 2 development for breast cancer that has metastasized to the brain and is completing a Phase 1 study in patients with primary brain cancer. The FDA has granted Orphan Drug designation to berubicin for the treatment of brain tumors.

Background
Berubicin belongs to a novel class of anthracycline derivatives that cross the blood-brain barrier and show significant potential for the treatment of primary and secondary brain cancers. While other drugs in this class (for example, doxorubicin) are some of the most broadly used and effective cancer therapies, they do not cross the blood-brain barrier and are not effective in treating brain tumors.

These compounds are potent inhibitors of topoisomerase II, a DNA repair enzyme. Overexpression of topo II has been identified as an indicator of aggressive cell proliferation and a negative prognostic indicator in patients with primary brain cancers. Topo II inhibition is likely to be effective in combination with temozolomide, the current standard therapy in glioblastoma.

Primary Brain Tumor Program
Primary brain tumors, particularly glioblastoma multiforme (GBM), represent an area of high unmet medical need. These tumors take a devastating toll on the lives of patients and their families. The need for new therapies is evident from the relatively poor median survival of GBM patients, which is just over one year.

Berubicin is being studied in an ongoing Phase 1 trial in patients with recurrent primary brain tumors at leading U.S. neurooncology centers. In this study, several patients experienced shrinking of their tumors (known as objective tumor responses), including one patient with an ongoing Complete Response of over two years duration. The safety profile of berubicin in this study was consistent with or better than other drugs in its class.

Metastatic Brain Tumor Program
Brain Metastases - cancers that have spread to the brain from another site such as the breast or lung - affect approximately ten times as many people as primary brain tumors. The only treatment currently available for these patients is radiation therapy, which is associated with significant side effects and does not have a meaningful impact on survival. As medical innovations have increased the life span of patients with a variety of forms of cancer, the incidence of brain metastases is increasing, and is often the cause of death in patients that have survived their initial bout with cancer.

There is a strong biological rationale for studying berubicin in patients with metastatic brain tumors. This class of drugs is highly effective against many types of tumors, including many that commonly metastasize to the brain (for example, breast cancer). Previous clinical studies have shown that cytotoxic drugs that don't cross the blood-brain barrier can have a short-term effect on brain metastases. Thus, agents that do have this property are believed to have much greater potential to provide a meaningful clinical benefit to patients with brain metastases.

Reata is currently conducting a Phase 2 clinical trial of berubicin in patients whose breast cancer has metastasized to the brain. A second Phase 2 trial in patients with brain metastases from lung cancer is also under active development.