BeiGene's zebratinib was approved for clinical trials

BRUKINSA ® is the only Bruton's tyrosine kinase inhibitor (BTKi) that exhibits progression-free survival (PFS) compared to ibrutinib ®

On January 20, 2023, BeiGene announced that the U.S. Food and Drug Administration (FDA) has approved its Bruton's tyrosine kinase (BTK) inhibitor, BRUKINSA ® (zebrutinib), for the treatment of adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

Mehrdad Mobasher, M.D., Chief Medical Officer of BeiGene's Hematology, said:

BRUKINSA ® obtained four marketing approvals in the U.S. in just over three years and demonstrated efficacy over ibrutinib in the final PFS analysis of the ALPINE study. Based on these results, we believe BRUKINSA ® can be the BTK inhibitor of choice for multiple indications." WE ARE ENCOURAGED BY THE PATIENTS WHO PARTICIPATED IN THE ALPINE AND SEQUOIA TRIALS, WHICH LED TO THE APPROVAL OF THIS NEW INDICATION AND THE BENEFITS OF THIS DRUG TO MORE PATIENTS."

The approval in the U.S. is based on two global Phase 3 clinical trials demonstrating BRUKINSA's ® efficacy and favorable safety profile in CLL patients:

In the SEQUOIA trial, with a median follow-up of 26.2 months, BRUKINSA ® demonstrated a significant PFS advantage over bendamustine plus rituximab in first-line patients with CLL (HR 0.42, [95% CI: 0.28 to 0.63], p< 0.0001) as assessed by an independent review committee (IRC) [i].

In the ALPINE trial, BRUKINSA ® achieved a more effective overall response rate than ibrutinib in patients with relapsed/refractory (R/R) CLL (ORR 80.4 versus 72.9%, p=0.0264) as assessed by IRC [ii].

BRUKINSA'S ® OVERALL SAFETY PROFILE IN THE ALPINE AND SEQUOIA TRIALS IS CONSISTENT WITH PREVIOUS STUDIES.

Among the pooled safety population of CLL patients treated with BRUKINSA ® (including all clinical development programs, N = 1,550), the most common adverse reactions (≥30%) included low neutrophil count (42%), upper respiratory tract infection (39%), low platelet count (34%), bleeding (30%), and musculoskeletal pain (30%) [iii].

The results of the final PFS analysis pre-set from the ALPINE trial demonstrated the efficacy and better cardiac safety profile of BRUKINSA ® compared to EKE ® in patients with R/R CLL. The results were presented orally in the latest breakthrough summary session of the 64th American Society of Hematology Annual Meeting and published simultaneously in the New England Journal of Medicine. With a median follow-up of 29.6 months, BRUKINSA ® showed PFS superior to ibrutinib in patients with R/R CLL (investigator and IRC assessment: HR: 0.65, [95% CI, 0.49~0.86], p=0.0024). In addition, BRUKINSA exhibited good cardiac safety profiles, with a significantly lower incidence of atrial fibrillation/atrial flutter in the BRUKINSA ® ® group (5.2 versus 13.3 percent) and zero in the BRUKINSA ® group versus six (0 versus 1.9 percent) in the ibrutinib group [iv, v].

Jennifer R. Brown, MD, director of the CLL Center in the Hematology Oncology Division at Dana-Farber Cancer Institute, said:

We have seen exciting data from BRUKINSA development projects demonstrating that BRUKINSA ® ® has demonstrated significant and consistent efficacy in patients with all CLL subtypes, regardless of treatment context; These subtypes include people at high risk for del 17p or TP53 mutations. WITH EXTENSIVE FOLLOW-UP DATA FROM THE CLEL DEVELOPMENT PROGRAM, AND THE COMBINED RESULTS OF THE SEQUOIA AND ALPINE TRIALS, BRUKINSA ® IS BEING ESTABLISHED AS THE NEW STANDARD OF CARE FOR CLALL.

Brian Koffman, M.D., Chief Medical Officer and Executive Vice President of the CLL Society, said:

Tolerance of the drug is also an important consideration thanks to research that leads to innovative and effective drugs that allow patients with CLL to achieve long-term survival under treatment. The approval of BRUKINSA ® provides patients with CLL/SLL with a well-proven treatment option for BTK inhibitors with proven efficacy and good long-term tolerability.

About BRUKINSA ®:

BRUKINSA ® is a small molecule inhibitor of Bruton's tyrosine kinase (BTK) independently developed by BeiGene scientists and is currently undergoing extensive clinical trials worldwide as a single agent and in combination with other therapies for the treatment of a variety of B-cell malignancies. BRUKINSA's ® design achieves targeted, sustained inhibition of BTK proteins by optimizing bioavailability, half-life and selectivity. With differentiated pharmacokinetic profiles with other approved BTK inhibitors, BRUKINSA ® has been shown to inhibit malignant B cell proliferation in multiple disease-associated tissues.

BRUKINSA ® has conducted extensive global clinical development programs and has conducted 35 trials in more than 30 locations around the world, enrolling more than 4,700 participants. To date, BRUKINSA ® has been approved in more than 60 markets, including the United States, China, the European Union and Great Britain, Canada, Australia, South Korea, Iceland, Norway and Switzerland.