EMA Grants Orphan Drug Designation to Annamycin in AML


The European Medicines Agency has granted orphan drug designation to annamycin for the treatment of patients with acute myeloid leukemia.

Walter Klemp

Walter Klemp

The European Medicines Agency (EMA) has granted orphan drug designation to the next-generation anthracycline annamycin as a potential treatment option for patients with relapsed/refractory acute myeloid leukemia (AML).1

Unlike other anthracyclines, annamycin is designed to be non-cardiotoxic, as demonstrated in the 82 patients treated across multiple studies evaluating the agent in the United States and Europe.1

Notably, the phase 1b/2 MB-106 trial (NCT05319587), which is simultaneously being conducted in both the United States and Europe, is examining the efficacy of annamycin alongside cytarabine for this patient population, and it elicited a preliminary composite complete response (CRc) rate of 60% among patients treated in the second-line (n = 10), and an interim CRc rate of 39% across all patients (n = 18), irrespective of prior treatment history. 

Follow-up regarding the durability of these CRcs is ongoing, with 1 patient maintaining a CR beyond 1 year. Enrollment for second-line patients in MB-106 has concluded; however, recruitment for first- and third-line patients is ongoing. Additionally, in the first-line setting, 2 evaluable patients had a CRc rate of 50%, and 1 patient achieved a CR.1,2

"We are pleased to receive orphan drug designation from the EMA for annamycin, which further supports our ongoing efforts to advance this compelling next-generation anthracycline for the treatment of hard-to-treat cancers," Walter Klemp, chairman and chief executive officer of Moleculin, stated in a press release.1 "Combined with the orphan drug designation we already have in the United States and with the new composition of matter patent just awarded by the US Patent and Trademark Office with coverage through 2040, we believe the commercial exclusivity of annamycin is now very well protected.”

The multicenter, open-label, dose-escalation trial is ongoing, enrolling patients with AML at least 18 years of age. Eligible patients must have confirmed demonstrating myeloblasts at a level exceeding 5%. Additionally, patients may present as treatment naive or have relapsed/refractory disease following induction therapy with more than 5% bone marrow blasts. Furthermore, patients must have an ECOG performance status of 0 to 2 and meet predefined laboratory criteria.3

Exclusion criteria include the presence of acute promyelocytic leukemia, prior mediastinal radiotherapy, central nervous system involvement, and specific cardiac conditions such as a left ventricle ejection fraction below 50%, valvular heart disease, or severe hypertension.3

Upon enrollment, patients receive treatment consisting of liposomal annamycin administered intravenously over a 2-hour period once daily for the initial 3 days of each 21-day cycle with 2.0 g/mg2 of cytarabine administered for 5 consecutive days during the first cycle.3

The primary end points of the study are to assess the safety profile of the treatment regimen and determine the maximum tolerated dose or recommended phase 2 dose. Secondary end points include evaluating pharmacokinetics and assessing the anti-leukemia activity of the therapy. This comprehensive approach aims to provide valuable insights into the efficacy and safety of this treatment regimen for AML patients.3

Annamycin is undergoing development for treatment of AML, as well as the treatment of lung metastases, though Moleculin Biotech posits that the drug may hold promise for treating additional medical conditions.1

“We continue to be encouraged by the growing body of promising interim clinical data demonstrated by Annamycin. We remain focused on advancing our clinical and regulatory strategies toward our next phase of development, including the planned commencement of a pivotal registration study as a second-line therapy in AML before year end,” Klemp said in the press release.1


  1. European Medicines Agency (EMA) grants orphan drug designation for Moleculin's treatment of acute myeloid leukemia (AML). News release. April 18, 2024. Accessed April 18, 2024. https://moleculin.com/european-medicines-agency-ema-grants-orphan-drug-designation-for-moleculins-treatment-of-acute-myeloid-leukemia-aml/
  2. Moleculin announces positive interim data in annamycin MB-106 phase 1B/2 AML trial. News release. Moleculin Biotech. March 25, 2024. Accessed April 18, 2024. https://moleculin.com/moleculin-announces-positive-interim-data-in-annamycin-mb-106-phase-1b-2-aml-trial/
  3. Study of liposomal annamycin in combination with cytarabine for the treatment of subjects with acute myeloid leukemia (AML). ClinicalTrials.gov. Updated November 18, 2023. Accessed April 18, 2024. https://www.clinicaltrials.gov/study/NCT05319587
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