FDA Guidance Enables Moleculin to Streamline Phase 3 Trial for Novel AML Treatment AnnAraC

Key Insights

• Moleculin Biotech receives FDA feedback allowing a 10% reduction in Phase 3 trial size for AnnAraC, their combination therapy targeting refractory/relapsed Acute Myeloid Leukemia.
• The MIRACLE Phase 3 study will evaluate high-dose cytarabine combined with two different doses of Annamycin (190 mg/m2 and 230 mg/m2) against placebo in 75-90 initial subjects.
• Annamycin holds Fast Track Status and Orphan Drug Designations from both FDA and EMA, with preliminary efficacy data expected in second half of 2025.

Moleculin Biotech has received crucial FDA feedback that will accelerate the development pathway for their promising blood cancer therapy. The regulatory guidance enables a streamlined approach to their Phase 3 pivotal trial evaluating Annamycin in combination with Cytarabine (AnnAraC) for patients with refractory/relapsed Acute Myeloid Leukemia (AML).

The FDA's recommendations for modifications to the statistical plan will allow Moleculin to reduce Part B of their trial by approximately 10% while maintaining the study's core elements. Walter Klemp, Chairman and Chief Executive Officer of Moleculin, emphasized the significance of this development: "The nature of the feedback helps us move forward quickly to open sites in the US, in addition to the sites we are expecting to open in Europe and the Middle East. All of this supports the pursuit of an accelerated timeline for new drug approval."

Trial Design and Implementation

The MIRACLE Phase 3 study employs an adaptive design strategy, initially enrolling 75 to 90 subjects in Part A. These participants will be randomized to receive high-dose cytarabine (HiDAC) combined with either placebo or Annamycin at two FDA-recommended doses - 190 mg/m2 or 230 mg/m2.

A notable feature of the amended protocol is the inclusion of two unblinding points. The first analysis will occur at 45 subjects, comprising 30 subjects receiving Annamycin (at either dose) plus HiDAC and 15 subjects receiving HiDAC with placebo. The second unblinding will take place at the conclusion of Part A. These strategic analysis points are scheduled for the second half of 2025 and first half of 2026, respectively.

Regulatory Status and Trial Progression

Part B of the trial will enroll approximately 220 additional subjects, who will be randomized to receive either HiDAC plus placebo or HiDAC plus the optimum dose of Annamycin determined from Part A. The development program has already secured significant regulatory support, with Annamycin holding both Fast Track Status and Orphan Drug Designation from the FDA for relapsed or refractory acute myeloid leukemia and soft tissue sarcoma. Additionally, the European Medicines Agency has granted Orphan Drug Designation for the AML indication.

The market has responded enthusiastically to these developments, with Moleculin's stock (MBRX) experiencing a dramatic increase of 426% to $2.21, accompanied by exceptional trading volume of 64.85 million shares compared to its average of 157,048.