RTA-477 for glioblastoma and brain metastases – pro

Lay Summary: RTA-477 is a promising but experimental treatment at this time.

RTA 744 is a novel anthracycline that is completing Phase 1 testing. This agent has been well tolerated and has demonstrated excellent activity against brain tumors. Advanced clinical trials of RTA 744 in both primary and secondary (metastatic) brain cancers will be initiated during the second half of 2007. The FDA has granted Orphan Drug designation to RTA 744 for the treatment of brain tumors.

Thise compounds is a potent inhibitors of topoisomerase II, a DNA repair enzyme. RTA 744 has been studied in a a Phase 1 trial in patients with recurrent primary brain tumors at the University of Texas M. D. Anderson Cancer Center, the University of Texas Southwestern Medical Center at Dallas and the UCLA School of Medicine. As reported at the Society for Neuro-Oncology annual meeting in November 2006, RTA 744 demonstrated appropriate pharmacokinetics and a safety profile consistent with or somewhat better than other drugs in its class.

Most importantly, RTA 744 has produced positive signs of anti-cancer activity in multiple patients with recurrent GBM.  In particular, one patient who began receiving RTA 744 in January 2006 experienced complete tumor abrogation as measured by repeated MRI imaging (known as a “Complete Response”) and remains tumor free as of April, 2007. Complete Responses are exceedingly rare in this patient population, and indicate that a drug is highly active against this particularly deadly and debilitating form of cancer. Several other patients have also seen their tumors shrink or stabilize upon treatment with RTA 744.

Based on the encouraging results seen to date, Reata started clinical trials of RTA 744 in patients with GBM and brain metastases during the second half of 2007.

C. A. Conrad et al, Survival study of RTA 744 (currently a single agent phase I study) alone and in combination with temozolomide in orthotopic model of glioma Journal of Clinical Oncology, 2006 ASCO Annual Meeting Proceedings (Post-Meeting Edition). Vol 24, No 18S (June 20 Supplement), 2006: 1577

R. Kazerooni et al, Phase I clinical pharmacokinetics of RTA 744: A blood brain barrier penetrating anthracycline active against high-grade glioma Journal of Clinical Oncology, 2007 ASCO Annual Meeting Proceedings (Post-Meeting Edition). Vol 25, No 18S (June 20 Supplement), 2007: 2045

nccn.org, brain cancer

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