The U.S. Food and Drug Administration (FDA) has cleared the way for MEI Pharma to launch a Phase 1 study of voruciclib, its oral CDK9 inhibitor, to treat people with relapsed or refractory B-cell malignancies.
The FDA’s approval of the company’s investigational new drug (IND) application for the treatment means MEI Pharma can initiate a clinical trial to determine voruciclib’s preliminary clinical activity, safety, tolerability, pharmacokinetics ((how the body metabolizes, distributes, and excretes a medicine) and pharmacodynamics (the effect the treatment has on the body).
Voruciclib is an orally available cyclin dependent kinase 9 (CDK9) inhibitor that has shown in preclinical studies that it can suppress MCL-1 function at doses that appeared to be well tolerated by patients. MCL-1 is a protein that, in humans, is encoded by the MCL1 gene. Studies have shown that MCL-1 is an established resistance mechanism to the B-cell lymphoma inhibitor Venclexta (venetoclax), developed by Genentech.
“Inhibiting the function of certain CDK family members has shown significant clinical activity in breast cancer. Voruciclib inhibits CDK9 which controls expression of MCL-1, a known mechanism of resistance to apoptosis,” Daniel P. Gold, PhD, president and chief executive officer of MEI Pharma, said in a press release.
“Therefore, voruciclib alone or in combination with a BCL-2 inhibitor such as venetoclax offers a potential novel approach for treatment of B-cell malignancies. With the FDA clearance of our IND, we look forward to advancing voruciclib through the clinic in the second quarter of 2018 to demonstrate its clinical and commercial value.”
Voruciclib was developed in collaboration with researchers at Presage Biosciences, after MEI Pharma signed a collaboration agreement in September 2017. Under the terms of the agreement, MEI Pharma acquired exclusive worldwide rights to develop, manufacture, and commercialize voruciclib.
To date, voruciclib has been studied in more than 70 patents in several Phase 1 studies and has been associated with manageable side effects, consistent with other drugs in its class. In preclinical studies, voruciclib as a stand-alone therapy induced cell death in multiple patient-derived chronic lymphocytic leukemia (CLL) samples.
MEI is now preparing to initiate a Phase 1/2 clinical study of voruciclib as a single agent and in combination with Venclexta in refractory CLL.