FDA Grants Fast Track Designation to Next-Generation Anthracycline for STS Lung Metastases

The FDA has granted fast track designation to Annamycin for the treatment of soft tissue sarcoma (STS) lung metastases, according to a press release from Moleculin Biotech, Inc.¹

In a preclinical study, Annamycin achieved high in vivo activity in lung metastatic cancer models.² It was shown that Annamycin had high cytotoxic potency and could overcome ATP-binding cassette transporter-mediated efflux and achieve a high intracellular uptake compared with a similar agent, doxorubicin (Adriamycin). The concentration of Annamycin in the lungs was 6 times greater than doxorubicin, allowing Annamycin to demonstrate in vivo efficacy in lung-localized tumor models. The impact of Annamycin occurred on a cellular level, according to an immunofluorescence and fluorescence activated cell sorting analysis. Overall, the analysis showed a significantly higher uptake of Annamycin in the lungs compared with doxorubicin.¹

The activity observed ranged from inhibition of tumor progression to complete tumor eradication in bioluminescent imaging in models of lung-localized cancer metastases.

Subjects in the sarcoma lung metastasis model had a median survival of 87.5 days with annamycin versus only 21 days with saline. The survival ratio observed was 4.17 with annamycin versus 1 with saline (P < .0001).

"We are pleased to receive our second fast track designation from the FDA for Annamycin. We now have potential pathways for accelerated approval in 2 indications, STS lung metastases, and the treatment of relapsed or refractory acute myeloid leukemia [AML]," commented Walter Klemp, chairman, and chief executive officer, Moleculin Biotech, Inc, in the press release. "Not only does this make us eligible for accelerated approval and priority review for our new drug application submission, but it serves as an important reminder of the unmet need in STS lung metastases.”

With a fast track designation, the company will be eligible to have more frequent discussions with the FDA about the development of Annamycin and the design of clinical trials involving the drug. The agent will also be eligible for an accelerated approval given that it meets the efficacy and safety criteria. Moleculin Biotech may also opt for a rolling submission, which allows the company to submit small portions of a biologics license application or new drug application at a time.

An unmet medical need exists for patients with STS and lung metastases. These metastases are found in 20% to 50% of soft tissue sarcomas, and it is challenging to find treatment options for these patients. After the cancer metastasizes to the lung, chemotherapy is administered if the lesions cannot be surgically removed. Initially, 10% to 30% of patients respond to doxorubicin, but they relapse with no chemotherapy agent to replace it. Cardiotoxicity is another barrier to finding an effective treatment for patients with STS and lung metastases.

Annamycin is a next-generation anthracycline agent. Annamycin has been shown to accumulate in the lungs at up to 30-fold the level of the current standard-of-care treatment, doxorubicin. In addition, the agent results in less cardiotoxicity, according to finding from in-human clinical trials of patients with AML, signaling that the drug may have fewer treatment limitations than doxorubicin. Annamycin is under continued investigation as a treatment of relapsed or refectory AML, brain tumors, pancreatic cancer, and hematologic malignancies, including cutaneous T-cell lymphoma.

_References:

_{1. Moleculin receives FDA approval of fast track designation for annamycin in the treatment of sarcoma lung metastases. News release. Moleculin Biotech, Inc. March 30, 2021. Accessed March 31, 2021. https://prn.to/39wCAwJ}

_{2. Zielinski R, Grela K, Zuniga RC, et al. Targeting sanctuary sites of cancer: Novel approaches to treatment of lung localized tumors. Poster presented at: 2020 AACR Annual Meeting; June 22-24, 2020; Virtual. Abstract 3074.}