Annamycin Achieves 80% ORR in Relapsed/Refractory Acute Myeloid Leukemia

Topline results from the phase 1 European MB-105 clinical trial (NCT03388749) showed that new safety results for annamycin, a next-generation anthracycline, are in keeping with previous findings for patients with relapsed/refractory acute myeloid leukemia (AML). Moreover, the agent induced an overall response rate (ORR) of 80%.¹

Investigators in the open-label, single-arm trial observed 1 complete response with incomplete recovery of peripheral blood count (CRi) and 3 partial responses (PR). In this cohort, dosed at 240 mg/m², the age range at time of treatment of the 5 subjects was 62 to 73 years. CR was defined as bone marrow blasts reduced to 5% or less. CRi was defined as incomplete recovery of white blood cell and/or platelet counts.

“We are very pleased with these topline results, both in terms of safety and the initial data suggesting efficacy, especially since these patients were relapsed or refractory,” Moleculin chairman and chief executive officer Walter Klemp, said in a news release.

An independent expert observed no cardiotoxicity in the trial. The most frequently reported adverse effects, occurring in at least 10 % of patients, were neutropenia, thrombocytopenia, and anemia.

“We also are encouraged by the absence of cardiotoxicity with Annamycin to date,” Klemp added. “This is particularly relevant in light of a recently published retrospective study showing that the incidence of heart failure more than doubles for cancer patients treated with anthracyclines compared to cancer patients not receiving anthracyclines. Annamycin was designed to be non-cardiotoxic, and we believe the initial safety data, if replicated along with efficacy data as our development work continues, suggest an opportunity for Annamycin to become a preferred anthracycline treatment for AML and other indications."

A total of 20 patients aged a median of 64.5 years (range, 24-76) were enrolled. The median number of prior therapies for all patients was 4 (range, 1-18). Seventeen patients received the full 3 consecutive days of dosing per protocol.

Patients in earlier cohorts received annamycin at 120 mg/m² or at 180 mg/m². Two of whom, 1 at each dose level, exhibited a 50% decrease in marrow blasts and marrow blasts less than 25% but did not meet what the protocol defined as a PR at that time.

Per protocol at that time these patients were required to have normalization of blood counts/hematologic values in addition to bone marrow blast reduction to qualify as a PR, which did not occur. The final version of the protocol required just a 50% or greater reduction in marrow blasts to qualify as a PR. Although these 2 patients were allowed to receive a second cycle of treatment, they were recorded as having a best overall response of “treatment failure.”

In findings from a retrospective population-based case-control study of 2196 participants, 812 with breast cancer or lymphoma, investigators found that anthracyclines were associated with an increased risk for congestive heart failure (CHF) compared with patients who did not receive them (HR, 1.78; 95% CI, 0.83-3.81; P = .14). Moreover, the risk persisted over time. At 15 years of follow-up, investigators found that the cumulative incidence of CHF in patients who received anthracyclines was more than 2-fold greater than those who did not (7.42% vs 3.18%).²

The FDA granted an orphan drug designation to annamycin for the treatment of patients with soft tissue sarcomas in December 2020. Preclinical data presented at the virtual 2020 AACR Annual Meeting II, as well as data from an independent laboratory announced in October 2020, demonstrated that annamycin is capable of reaching 6- to 34-fold higher levels of accumulation in the lungs compared with doxorubicin.³

References

1. Moleculin announces final topline data from successful european phase 1 trial evaluating annamycin as single agent treatment of relapsed or refractory acute myeloid leukemia (AML). Moleculin. News release. February 13, 2023. Accessed February 13, 2023. https://moleculin.com
2. Larsen CM, Garcia Arango M, Dasari H, et al. Association of anthracycline with heart failure in patients treated for breast cancer or lymphoma, 1985-2010. JAMA Netw Open. Published online February 1, 2023. doi:10.1001/jamanetworkopen.2022.54669
3. Moleculin announces annamycin receives FDA orphan drug designation for soft tissue sarcomas. Moleculin. News release. December 29, 2020. Accessed February 13, 2023. https://www.prnewswire.com