The U.S. Food and Drug Administration (FDA) has accepted for review BeiGene‘s application requesting the approval of zanubrutinib for treating people with mantle cell lymphoma who received at least one prior therapy.
The FDA had granted zanubrutinib a breakthrough therapy designation for the same indication earlier this year. In addition to giving access to more intensive FDA guidance for product development, that made the treatment eligible for priority review.
“We are proud to have submitted our first NDA in the U.S., 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,” Jane Huang MD, chief medical officer of hematology at BeiGene, said in a press release.
The investigational therapy is a small molecule that blocks Bruton’s tyrosine kinase (BTK), a protein that helps B-cells stay alive and divide. By blocking BTK, zanubrutinib promotes B-cell death and halts cancer progression.
“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,” Huang said.
The new drug application was supported by the results of a Phase 1 trial (NCT02343120) testing zanubrutinib in different subtypes of B-cell lymphoma, including mantle cell lymphoma. Data also came from a Phase 2 trial (NCT03206970) testing the treatment in relapsed or refractory mantle cell lymphoma patients in China.
Results from that Phase 2 trial were presented in June at the 15th International Conference on Malignant Lymphoma, held in Switzerland. In that trial, 72 of the 85 (84.7%) mantle cell lymphoma patients responded to treatment, including 65 (76.5%) who had no signs of lymphoma cells after taking zanubrutinib.
Participants responded to zanubrutinib for a median of 14 months, and lived without signs of disease worsening for a median of 16.7 months.
Only eight patients discontinued treatment due to adverse events, which included infections, bleeding in the gastrointestinal tract, brain bleeding, interstitial lung disease, and low platelet levels.
The application also includes safety data from five zanubrutinib clinical trials, as well as non-clinical data.
Besides mantle cell lymphoma, zanubrutinib is being tested for several other blood cell cancers. These include the ALPINE Phase 3 trial (NCT03734016) for refractory or relapsed chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), and the ASPEN Phase 3 trial (NCT03053440) for Waldenström macroglobulinemia, a kind of B-cell non-Hodgkin’s 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,” Huang added.
Zanubrutinib received fast track designation from the FDA for people with Waldenström macroglobulinemia. It is being reviewed in China as a potential treatment for people with mantle cell lymphoma or CLL/SLL whose cancer progressed after receiving at least one prior treatment.