FDA Pipeline: Designations for Myelodysplastic Syndromes, Triple-Negative Breast Cancer, AML, and EBV-Associated Cancers


Over the past week, the U.S. Food and Drug Administration (FDA) granted several Fast Track and Orphan Drug designations to treatments for myelodysplastic syndromes, triple-negative breast cancer, acute myeloid leukemia (AML), and Epstein-Barr virus (EBV)-associated cancers.

Fast Track Designation and Orphan Drug Designation for APR-246 for the Treatment of Myelodysplastic Syndromes

The FDA granted Fast Track designation to APR-246 for the treatment of patients with TP53-mutated myelodysplastic syndromes. In addition, the FDA granted Orphan Drug designation to APR-246 for the treatment of myelodysplastic syndromes.

The TP53 tumor-suppressor gene is the most frequently mutated gene in human cancers, occurring in approximately 50% of all human tumors. These mutations are often associated with resistance to anticancer drugs and poor overall survival, representing a major unmet medical need in the treatment of cancer.

APR-246 has been shown to reactivate mutant and inactivated p53 protein by restoring wild-type p53 conformation and function, thereby inducing programmed cell death in human cancer cells. APR-246 has demonstrated preclinical antitumor activity in a wide variety of solid and hematologic cancers. Additionally, strong synergy has been seen with both traditional anticancer agents, such as chemotherapy, as well as newer mechanism-based anticancer drugs and immuno-oncology checkpoint inhibitors. In addition to preclinical testing, a phase I/II clinical program with APR-246 has been completed, demonstrating a favorable safety profile, biologic activity, and clinical responses in hematologic malignancies and solid tumors with mutations in the TP53 gene.

Fast Track Designation for INT230-6 in Relapsed or Metastatic Triple-Negative Breast Cancer

The FDA granted Fast Track designation to a development program evaluating INT230-6 for the treatment of patients with relapsed or metastatic triple-negative breast cancer who have failed at least two prior lines of therapy. INT230-6, designed for direct intratumoral injection, comprises two proven, potent anticancer agents and a penetration enhancer molecule that helps disperse the drugs throughout tumors and diffuse into cancer cells.

INT230-6 is being evaluated in a phase I/II clinical study in patients with various advanced solid tumors. In preclinical studies, INT230-6 eradicated tumors by a combination of direct tumor kill and recruitment of dendritic cells to the tumor microenvironment that induced anticancer T-cell activation.

Fast Track Designation for Annamycin in AML

The FDA granted Fast Track designation for annamycin for the treatment of relapsed or refractory AML. Annamycin, a next-generation anthracycline, is designed to avoid multidrug resistance mechanisms with little to no cardiotoxicity. It is being studied for the treatment of relapsed or refractory acute myeloid leukemia.

Orphan Drug Designation for Nanatinostat in EBV-Associated Cancers

The FDA granted Orphan Drug designation to nanatinostat (VRx-3996) in combination with the antiviral valganciclovir for the treatment of posttransplant lymphoproliferative disorder, plasmablastic lymphoma, and angioimmunoblastic T-cell lymphoma. The therapeutic approach is being investigated in a phase Ib/II clinical trial of Epstein-Barr virus (EBV)-associated lymphomas.

Nanatinostat is an oral histone deacetylase inhibitor that is being investigated in a range of clinical indications. Valganciclovir is an antiviral medication used for the treatment of EBV-associated cancers.

Approximately 95% of the world's adult population is infected with EBV. Infections are commonly asymptomatic or associated with mononucleosis. Following infection, the virus remains latent in a small subset of lymphatic cells for the duration of the patients' life. Cells containing latent virus are increasingly susceptible to malignant transformation. Patients who are immunocompromised are at an increased risk of developing EBV lymphomas. In addition, EBV is also associated with a variety of solid tumors, including nasopharyngeal carcinoma and gastric cancer.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.