European Medicines Agency Grants Approval To Moleculin To Expand Phase 3 MIRACLE Trial, Advancing Cancer Research

Moleculin Biotech, Inc., a late-stage pharmaceutical company with a portfolio of drug candidates targeting difficult-to-treat cancers and viral infections, has announced that the European Medicines Agency (EMA) has approved its Clinical Trial Application (CTA) for the pivotal Phase 2B/3 study of Annamycin in combination with cytarabine (Ara-C), known as AnnAraC. This multi-center, randomized, double-blind, placebo-controlled, adaptive design trial will focus on treating adult patients with relapsed or refractory acute myeloid leukemia (R/R AML) who have not responded to or have relapsed after induction therapy. The approval applies across nine countries in the European Union (EU), and the study will also include sites in the US, Europe, and the Middle East.

The study, referred to as the MIRACLE trial (Moleculin R/R AML AnnAraC Clinical Evaluation), combines a Phase 2B portion with a Phase 3 segment to evaluate the efficacy and safety of AnnAraC. The initial part of the study will involve randomizing the first 75 to 90 subjects to receive high-dose cytarabine (HiDAC) in combination with either a placebo or two different doses of Annamycin (190 mg/m² or 230 mg/m²), as recommended by the FDA after the company's end-of-Phase 1B/2 meeting.

Walter Klemp, Chairman and CEO of Moleculin, stated, “EMA approval of the MIRACLE trial protocol is a huge milestone for us. Although we’re already seeing recruitment in our first non-EU country, we believe that this expansion into the EU really supercharges our recruitment potential. Importantly, when combined with the sites we are opening in the US, this approval from the EMA, along with the individual country committee and/or ethics approvals, for Belgium, Czechia, France, Germany, Italy, Lithuania, Poland, Romania, and Spain positions us to remain on track with our expected enrollment and data milestones.”

Mr. Klemp added further,  “Being accepted in all nine of the countries for which we submitted, we believe indicates the magnitude of the need for a better answer for R/R AML patients, especially venetoclax regimen failures where the outcomes from currently available therapies are considered dismal in published studies. While there are minor differences between the US and EU protocols with the FDA and EMA, respectively, we do not view these as a barrier to conducting the study and are working to harmonize the protocols as appropriate. We are grateful for the international collaboration and believe it underscores the significant unmet need in R/R AML and the potential of Annamycin to provide a much needed second line treatment option. We remain focused on driving enrollment and patient dosing and look forward to reporting initial data on the first 45 subjects in the second half of 2025.”

An early unblinding of the data is planned after the first 45 subjects are treated, with results on primary efficacy (Complete Remission or CR) and safety being assessed. This unblinding will include data from 30 subjects receiving Annamycin (190 mg/m² or 230 mg/m²) with HiDAC, and 15 subjects receiving HiDAC plus placebo. The first data readout is expected in the second half of 2025, with a second unblinding in the first half of 2026. The accelerated timeline for these unblinding events follows positive discussions with potential investigators in December 2024, which helped streamline patient recruitment.

The EMA’s approval was granted with the condition that Moleculin submits results from appropriate nonclinical GLP studies before beginning the Phase 3 portion (Part B) of the trial. This data will be presented as a substantial modification to the existing approved protocol. For Part B, an additional 220 subjects will be randomized to receive either HiDAC plus placebo or HiDAC plus the optimal dose of Annamycin, with the dose selection based on safety, pharmacokinetics, and efficacy, aligning with the FDA’s Project Optimus initiative.

Patient dosing has already begun, and the company expects to present initial data in the second half of 2025. Annamycin, also known as naxtarubicin, has received Fast Track Status and Orphan Drug Designation from the FDA for relapsed or refractory AML and soft tissue sarcoma. Additionally, it holds Orphan Drug Designation from the EMA for relapsed or refractory AML.