First Patient Dosed With Annamycin and Cytarabine in Phase 3 AML Trial

The first patient with relapsed or refractory acute myeloid leukemia, or AML, has been dosed with annamycin in combination with cytarabine (also known as “Ara-C”) in the global phase 3 MIRACLE trial, according to a press release from Moleculin Biotech, Inc., which added that the trial has active sites in the United States, Europe and the Middle East.

The agent under investigation, annamycin, is a type of chemotherapy drug which is being studied for patients with relapsed or treatment-resistant acute myeloid leukemia, according to the Moleculin website. The company's website emphasizes that the agent has zero cardiotoxicity, allowing for investigators to exceed the currently set maximum lifetime dosing for an anthracycline which may improve efficacy. Moreover, research suggests it could be safer and more effective than current options for patients within this population.

Annamycin currently has multiple regulatory indications from the U.S. Food and Drug Administration (FDA). This includes Fast Track Status and Orphan Drug Designation for the treatment of relapsed or refractory acute myeloid leukemia, as well as Orphan Drug Designation for the treatment of soft tissue sarcoma. In regard to global regulatory status, annamycin has also received Orphan Drug Designation for relapsed or refractory acute myeloid leukemia treatment from the European Medicines Agency.

“The start of patient dosing represents a huge milestone for Moleculin and importantly, the acute myeloid leukemia community,” Walter Klemp, chairman and CRO of Moleculin, commented in the press release. “Our team remains focused on bringing clinical sites online in the United States, Europe and Middle East and enrolling patients to build on this momentum. With the progress made to date, we expect to unblind preliminary data from the first 45 subjects in the second half of this year, a near-term, potentially value-driving milestone that will provide key insight as we continue to advance annamycin’s development towards approval.”

More Information on the Phase 3 MIRACLE Trial

The phase 2b/3 MIRACLE study will combine data from the phase 2b portion with phase 3 to assess the primary patient responses and outcomes. The trial, pending necessary regulatory approvals and potential feedback from the FDA and international agencies, follows an adaptive design. In part A, the first 75 to 90 participants will be randomly assigned to receive high-dose cytarabine with either a placebo, or two different doses of annamycin which were recommended by the FDA following the company’s end-of-phase 1b/2 meeting. 

The study is designed to review results at two key stages to assess how well the treatment is working and how safe it is. The first review will happen after 45 participants have been treated — 30 receiving annamycin with high-dose cytarabine and 15 receiving only high-dose cytarabine. The second review will take place once 75 to 90 participants have completed this phase. The first set of results is expected in late 2025, with the second in early 2026.

In the next phase of the trial, approximately 220 more participants will be randomly assigned to receive high-dose cytarabine with either a placebo or the best-performing dose of annamycin. The final dose selection will be based on an evaluation of safety, how the drug moves through the body and its effectiveness.

For more news on cancer updates, research and education, don’t forget to subscribe to CURE®’s newsletters here.