Berubicin Granted Orphan Drug Designation for Treatment of Malignant Gliomas

The FDA granted Orphan Drug Designation to berubicin (formerly known as RTA 744), an anthracycline anticancer drug intended for the treatment of malignant gliomas.¹

“We are excited to continue to drive the development of berubicin and work towards addressing a critical unmet medical need. Glioblastoma currently has a dismal survival rate of only 14.6 months from its diagnosis. We believe berubicin, which based on limited clinical data appears to be the first anthracycline to cross over the blood-brain barrier in adults, provides a potentially novel therapy for the treatment of malignant gliomas,” stated Sandra Silberman, MD, PhD, chief medical officer, CNS Pharmaceuticals, in a press release.

Berubicin was investigated in a phase 1 study of patients with glioblastoma multiforme under prior developer Reata Pharmaceuticals. In March 2020, it was reported that out of 25 evaluable patients in the study, 11 (44%) had a statistically significant improvement in progression-free survival (PFS). The disease control rate of 44% was based on the percentage of patients who responded and those with stable disease (SD). There was also 1 patient in the initial trial who achieved a durable complete response to treatment with berubicin and was cancer free for more than 13 years.²

Based on data from the phase 1 study, CNS Pharmaceuticals submitted the application for Orphan Drug Designation to the FDA in April 2020. The company also announced that a phase 2 clinical trial would begin pending an FDA Investigational New Drug meeting, for which an application was filed in November 2019.^2-4

"We are pleased to receive Orphan Drug Designation for berubicin, our lead candidate. The designation provides berubicin with a special status that can accelerate its development to treat malignant gliomas, and provides CNS with the potential for market exclusivity upon the drug's approval," stated John Climaco, chief executive officer, CNS Pharmaceuticals, in a press release.¹ "In the phase 1 trial of berubicin to treat glioblastoma, one of the world's most aggressive cancers, under a prior developer, 44% of the patients demonstrated a significant improvement in progression-free survival, and one patient experienced a complete response. We look forward to continuing to execute on our strategic plan and initiating a phase 2 trial evaluating the effect of berubicin on patients with glioblastoma later this year."

In the phase 1 study, berubicin injection demonstrated tolerability at the maximum tolerated dose of 7.5 mg/m²/day over 2 hours for 3 consecutive days of every 3-week cycle. The patient who achieved a durable complete response received a dose of 2.4 mg/m²/day.

Anthracycline agents like berubicin activate natural processes to induce DNA damage in targeted cancer cells by interrupting the action of topoisomerase II, an enzyme that enables cell proliferation. In the phase 1 clinical trial, berubicin demonstrated this ability and the ability to cross the blood-brain barrier, warranting further study of the drug in patients with gliomas.

_References:

_{1. CNS announces the FDA has granted Orphan Drug Designation for brain cancer drug Berubicin. CNS Pharmaceuticals. News release. June 11, 2020. Accessed June 12, 2020. https://bit.ly/3dVPOn9}

_{2. CNS Pharmaceuticals announces brain cancer patient from Berubicin phase 1 trial remains cancer free. CNS Pharmaceuticals. News release. Mar 3, 2020. Accessed June 12, 2020. https://prn.to/37qyFPG.}

_{3. CNS Pharmaceuticals announces filing of FDA Orphan Drug Designation for brain cancer drug Berubicin. CNS Pharmaceuticals. News release. April 23, 2020. Accessed June 12, 2020. https://bit.ly/30xvbtv.}

_{4. CNS Pharmaceuticals filed request with FDA for pre-ind meeting for Berubicin. News release. CNS Pharmaceuticals. November 21, 2019. Accessed June 12, 2020. https://bit.ly/3hsUumH.}