The U.S. Food and Drug Administration (FDA) has accepted BeiGene’s New Drug Application (NDA) for zanubrutinib, also known as BGB-3111 for the treatment of patients with mantle cell lymphoma (MCL) who have received at least one prior therapy.
The FDA granted Priority Review for the NDA and has set a Prescription Drug User Fee Act (PDUFA) target action date of February 27, 2020. This follows the FDA’s Breakthrough Therapy designation for zanubrutinib in this setting earlier this year.
Zanubrutinib is an investigational small molecule inhibitor of Bruton’s tyrosine kinase (BTK), discovered by BeiGene scientists. The drug is currently being evaluated in a broad pivotal clinical program globally as a monotherapy and in combination with other therapies to treat various B-cell malignancies.
“Zanubrutinib, a potent and selective BTK inhibitor designed to maximize BTK occupancy and minimize off-target effects, has shown promise as a potential treatment for a number of B-cell malignancies,” explained Jane Huang, MD, Chief Medical Officer, Hematology, at BeiGene.
“We are proud to have submitted our first NDA in the United States, which has now been accepted and designated for Priority Review by the FDA for the treatment of patients with relapsed/refractory mantle cell lymphoma, an aggressive form of lymphoma. We are conducting a broad global clinical development program for zanubrutinib that currently consists of eight Phase 3 or potentially registration-enabling trials, including two head-to-head comparative trials, with approximately 1,500 patients treated across all programs.”
The NDA data package includes data from the global Phase I/II trial (NCT02343120) in patients with B-cell lymphomas and an aggregate of 123 patients in the multicenter Phase II trial of zanubrutinib in patients with relapsed or refractory (R/R) MCL in China (NCT03206970), as well as safety data on 641 patients from five clinical trials, and non-clinical data.
Lymphoma is a diverse group of malignancies that originates from B-, T- or NK- cells. Mantle cell lymphoma (MCL) is typically an aggressive form of non-Hodgkin lymphoma (NHL) that arises from B-cells originating in the “mantle zone.” In the United States, about 70,800 new cases of NHL were estimated in 2014, with MCL representing about six percent (about 4,200 cases) of all new cases of NHL.
MCL usually has a poor prognosis, with a median survival of three to four years, although occasionally patients may have an indolent course. Frequently, MCL is diagnosed at a later stage of disease.
Priority Review and Fast Track
The U.S. FDA grants Priority Review designation to applications for drugs that, if approved, would provide a significant improvement in safety or effectiveness of the treatment of serious conditions. Under Priority Review, the FDA aims to take action on the marketing application within six months of NDA acceptance, as compared to 10 months under standard review. Priority Review designation does not change the scientific/medical standard for approval or the quality of evidence necessary to support approval.
The American drug regulator has also granted Fast Track designation for the treatment of patients with WM, and Breakthrough Therapy designation for the treatment of adult patients with MCL who have received at least one prior therapy. The New Drug Applications (NDAs) in China for R/R MCL and R/R CLL/SLL have been accepted by the China National Medical Products Administration (NMPA) and granted priority review.
Study of the Safety and Pharmacokinetics of BGB-3111 in Subjects With B-Cell Lymphoid Malignancies – NCT02343120
Study of Evaluate Efficacy and Safety of BGB-3111 in Subjects With Relapsed or Refractory Mantle Cell Lymphoma (MCL) – NCT03206970
 Mantle Cell Lymphoma Facts. Leukemia & Lymphoma Society. Online 2014. Last accesses August 22, 2019.
 Philip J. Bierman, James O. Armitage, in Goldman’s Cecil Medicine (Twenty Fourth Edition), 2012