Moleculin Biotech has amended the clinical trial protocol with the FDA for its Phase 3 pivotal MIRACLE trial evaluating Annamycin in combination with Cytarabine (Ara-C), referred to as AnnAraC, for relapsed or refractory acute myeloid leukemia (R/R AML). The amended protocol accelerates the unblinding of preliminary primary efficacy data and safety/tolerability of the three arms at the first 45 subjects.
The MIRACLE trial (Moleculin R/R AML AnnAraC Clinical Evaluation) is a global study with sites in the US. The company released a Virtual Investor segment discussing the amended protocol.
Accelerated Data Timeline
Walter Klemp, Chairman and CEO of Moleculin, stated that the amended protocol enables the company to share definitive data earlier, potentially accelerating the timeline for strategic partnering. The unblinding of data at 45 subjects will allow assessment of all three study arms, providing a clearer understanding of Annamycin's potential for AML patients. This change potentially puts the company less than 12 months away from definitive unblinded data.
The MIRACLE study will initially utilize an adaptive design where the first 75 to 90 subjects will be randomized in Part A to receive high-dose cytarabine (HiDAC) combined with either placebo, 190 mg/m2 of Annamycin, or 230 mg/m2 of Annamycin. The amended protocol allows for the unblinding of preliminary primary efficacy data (CR) and safety/tolerability of the three arms at 45 subjects. This early unblinding will yield 30 subjects with Annamycin (190mg/m2 and 230/m2) and HiDAC and 15 subjects with just HiDAC. The company expects to reach 45 subjects in the second half of 2025, in addition to the planned unblinding expected in 2026 of the next 30-45 subjects.
Trial Design and Optimization
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. The increase from 240 to 244 subjects represents the statistical "cost" of the additional unblinding.
The amended protocol is currently under review by the Institutional Review Board (IRB). Once approved, the amended protocol will be filed with the amendment for the company's Initial New Drug (IND) application in the US with the FDA.
Regulatory Status and Company Pipeline
Annamycin has Fast Track Status and Orphan Drug Designation from the FDA for relapsed or refractory AML, and Orphan Drug Designation for soft tissue sarcoma. It also has Orphan Drug Designation from the EMA for relapsed or refractory AML.
Moleculin Biotech is advancing a pipeline of therapeutic candidates for hard-to-treat tumors and viruses. Their lead program, Annamycin, is a next-generation anthracycline designed to avoid multidrug resistance and cardiotoxicity. The company is also developing WP1066, an Immune/Transcription Modulator targeting brain tumors, pancreatic, and other cancers, and a portfolio of antimetabolites, including WP1122 for pathogenic viruses and certain cancer indications.
