Annamycin Elicits Encouraging Responses in R/R Acute Myeloid Leukemia

Annamycin appeared to be effective and tolerable among patients with relapsed or refractory acute myeloid leukemia (AML), according to a press release on topline results from the European phase 1 MB-105 trial.¹

The FDA previously granted fast track and orphan drug designation to annamycin for managing soft tissue sarcoma lung metastases and relapsed or refractory acute myeloid leukemia.

In the final cohort, wherein all patients were at least 60 years old, annamycin produced 1 complete response with incomplete recovery of peripheral blood count (CRi) and 3 partial responses for an overall response rate of 80%. The patient who achieved a CRi was 65 years old at the time of treatment.

Investigators also reported that there was no cardiotoxicity among patients treated with annamycin. The most frequently reported adverse effects included neutropenia, thrombocytopenia, and anemia.

“We are very pleased with these topline results, both in terms of safety and the initial data suggesting efficacy, especially since the [population was] relapsed or refractory,” Walter Klemp, chairman and chief executive officer of Moleculin, said in the press release. “Given the recently published research showing that annamycin in combination with cytarabine substantially outperformed annamycin as a single agent in an aggressive AML mouse model, these topline results are encouraging as we continue to develop annamycin in combination with cytarabine for the treatment of AML.”

The European, open-label, single-arm phase 1 MB-105 trial was designed to assess the efficacy and safety of annamycin for patients with relapsed or refractory AML. Investigators concluded recruitment for the trial after determining a recommended phase 2 dose (RP2D) of 240 mg/m² of annamycin.

The primary end points of the trial included safety and identifying the maximum tolerated dose and RP2D.

The study included a total of 20 patients who were between the ages of 24 to 76 years. The median patient age was 64.5 years. The median number of prior therapies was 4 (range, 1-18). A total of 17 patients received 3 full, consistent days of dosing per protocol.

In an earlier cohort, 2 patients who were treated at the 120 mg/m² and 180 mg/m² dose levels did not qualify to receive a second cycle of treatment, although they demonstrated a marrow blast decrease of 50% or greater and marrow blast levels of less than 25%. Both patients had a best response of "treatment failure."

Following safety and dosage data from the MB-105 trial, investigators aim to conduct the phase 1/2 MB-106 trial evaluating annamycin plus cytarabine (Ara-C) for the management of relapsed or refractory AML.

“Having previously announced the start of our open label phase 1/2 MB-106 trial of annamycin in combination with cytarabine for the treatment of AML in Poland and Italy, we are optimistic about annamycin's potential for the treatment of AML as we continue to gather the data that ultimately will be necessary to support approval,” Klemp concluded.

The FDA previously granted fast track and orphan drug designations to annamycin for the treatment of soft tissue sarcoma lung metastases and relapsed or refractory AML.²

References

1. Moleculin announces final topline data from successful European phase 1 trial evaluating annamycin as a single agent treatment of relapsed or refractory acute myeloid leukemia (AML). News release. Moleculin Biotech. February 13, 2023. Accessed February 15, 2023. prn.to/3YuzLno
2. Moleculin receives FDA approval of fast track designation for annamycin in the treatment of sarcoma lung metastases. News release. Moleculin Biotech. March 30, 2021. Accessed February 15, 2023. https://prn.to/39t3khB