Moleculin Biotech has amended its Phase 3 clinical trial protocol with the FDA for Annamycin, in combination with cytarabine (AnnAraC), in patients with relapsed or refractory acute myeloid leukemia (R/R AML). The amended protocol for the "MIRACLE" trial (MB-108) accelerates the timeline for unblinding preliminary primary efficacy data and safety/tolerability assessments. The company expects to have definitive unblinded data in less than 12 months, potentially driving advanced partnering discussions.
Accelerated Data Readout
The MIRACLE trial is designed to evaluate Annamycin in combination with cytarabine for R/R AML. The amended protocol allows for unblinding of data after the first 45 subjects are treated, yielding data on 30 subjects treated with Annamycin and HiDAC and 15 subjects treated with HiDAC alone. This early unblinding will enable assessment of all three study arms: HiDAC plus placebo, HiDAC plus 190 mg/m2 Annamycin, and HiDAC plus 230 mg/m2 Annamycin.
Walter Klemp, Chairman and CEO of Moleculin, stated that the amended protocol allows the company to share definitive data earlier, which helps to partially de-risk financing the trial and potentially accelerates the timeline for strategic partnering. He believes that the unblinding of data at 45 subjects will enable the company to begin assessing all three arms of the study and provide a clear path forward in understanding the potential of Annamycin for AML patients.
Adaptive Trial Design
The MIRACLE study employs an adaptive design. The first 75 to 90 subjects will be randomized in Part A to receive HiDAC combined with either placebo, 190 mg/m2 of Annamycin, or 230 mg/m2 of Annamycin. The amended protocol will allow for the unblinding of preliminary primary efficacy data (CR) and safety/tolerability of the three arms at 45 subjects. For Part B of the trial, approximately 244 additional subjects will be randomized to receive either HiDAC plus placebo or HiDAC plus the optimum dose of Annamycin. The selection of the optimum dose will be based on the overall balance of safety, pharmacokinetics and efficacy, consistent with the FDA's new Project Optimus initiative.
Regulatory Status and Future Steps
Annamycin has been granted Fast Track Status and Orphan Drug Designation by the FDA for R/R AML, as well as Orphan Drug Designation for soft tissue sarcoma. It also holds Orphan Drug Designation from the EMA for R/R AML. The amended protocol is currently under review by the Institutional Review Board (IRB), and upon approval, it will be filed with the FDA as an amendment to the company's Initial New Drug (IND) application.
About Annamycin
Annamycin is a next-generation anthracycline designed to overcome multidrug resistance mechanisms and eliminate the cardiotoxicity associated with current anthracyclines. Moleculin Biotech is also developing WP1066, an Immune/Transcription Modulator, and a portfolio of antimetabolites, including WP1122, for potential treatment of pathogenic viruses and certain cancer indications.
