Moleculin Doses First European Patient In Phase 3 Pivotal MIRACLE Trial Evaluating New Therapy For Acute Myeloid Leukemia

Moleculin Biotech, Inc., a late-stage pharmaceutical company developing therapies for hard-to-treat cancers and viral infections, has announced that the first two subjects have been enrolled, and one has been treated, in the European Union in its pivotal Phase 2B/3 trial of Annamycin in combination with cytarabine (Ara-C). The study, known as the MIRACLE trial (Moleculin R/R AML AnnAraC Clinical Evaluation), is designed to evaluate the AnnAraC combination in adult patients with relapsed or refractory acute myeloid leukemia (R/R AML). The global trial, which includes sites in the U.S., the EU, and other regions, is a multi-center, randomized, double-blind, placebo-controlled study with an adaptive design.

According to Walter Klemp, Chairman and CEO of Moleculin, recruitment is underway in the U.S., Spain, Ukraine, Georgia, and Romania, with additional sites expected to open by the end of September. He noted that the quick enrollment at the first Spanish site underscores the significant unmet need for second-line therapies in R/R AML. The company aims to recruit the first 45 patients for Part A of the study by the end of 2025, at which point efficacy and safety data will be unblinded.

The MIRACLE trial combines Phase 2B and Phase 3 into a single design. In Part A, the first 75 to 90 patients will be randomized equally to receive high-dose cytarabine (HiDAC) plus either placebo, 190 mg/m2 of Annamycin, or 230 mg/m2 of Annamycin. These dose levels were recommended by the FDA following Moleculin’s end of Phase 1B/2 meeting. Preliminary efficacy, measured by complete remission rates, along with safety and tolerability data, will be assessed once 45 patients have been enrolled. This early unblinding is expected in the second half of 2025, with a second unblinding after 75 to 90 patients in the first half of 2026.

For the Phase 3 portion (Part B), approximately 220 additional patients will be randomized to receive either HiDAC plus placebo or HiDAC plus the optimal dose of Annamycin. Dose selection will be based on safety, pharmacokinetics, and efficacy, in line with the FDA’s Project Optimus initiative. The trial protocol also requires Moleculin to submit results from nonclinical GLP studies to European regulators before the initiation of Part B, which will be filed as a modification to the existing clinical trial authorization.

Annamycin, also known as naxtarubicin, has been granted Fast Track and Orphan Drug Designation by the FDA for relapsed or refractory AML, as well as Orphan Drug Designation for soft tissue sarcoma. The European Medicines Agency has also granted Orphan Drug Designation for Annamycin in R/R AML. Patient dosing in the MIRACLE trial has begun, and the first data readout remains on track for the second half of 2025.