The U.S. Food and Drug Administration (FDA) has granted orphan drug status to AB Science‘s investigational agent AB8939, a small molecule designed to treat acute myeloid leukemia (AML), the company announced.
This special status offers AB Science support for Phase 1 and Phase 2 clinical trials of AB8939, as well as a waiver from FDA’s prescription fees and seven years of marketing exclusivity in the U.S. should it be approved for AML.
It also entitles the company to a faster regulatory process if granted priority review or a breakthrough therapy designation.
The FDA’s decision was based on preclinical evidence of AB8939’s potential to improve AML treatment, in particular for patients whose cancer returned (relapsed) or who failed to respond (refractory) to prior treatments. These people have the poorest prognosis.
AB8939 is a new small molecule treatment that binds to and destabilizes microtubules — a major component of a cell’s “skeleton,” which is called the cytoskeleton. Microtubules support cell structure and mediate many crucial functions, including cell proliferation and the transport of substances within cells.
By dismantling microtubules, AB8939 aims to kill tumor cell lines at low doses. It has a different chemical structure and binding sites than other antimicrotubule agents used for chemotherapy. Due to this, it can avoid being transported by a protein transporter called P-glycoprotein (Pgp). This protein pumps treatments out of cancer cells, causing patients to develop multidrug resistance and fail to respond to chemotherapy.
By evading this transporter, AB8939 offers a potential new route of treatment for cancer and a way of overcoming treatment resistance.
AB8939 was designed to have strong antiproliferative properties and an acceptable safety profile with minimal cardiac or neuronal toxicity, AB Science states.
In laboratory tests, the compound was seen to be particularly active against hematopoietic tumor cell lines, such as cancers that affect the blood and lymph system, and against patient blasts, immature bone marrow cells commonly found in the blood of AML patients.
It showed a dose-dependent activity and efficacy against multidrug-resistant leukemia models, including those resistant to doxorubicin and cytarabine, commonly used to treat AML and other leukemias.
It also demonstrated significant anti-leukemic activity in mouse models of AML, prolonging animal survival.