FDA Gives Zanubrutinib Priority Review for Marginal Zone Lymphoma

This week, the FDA granted priority review to a supplemental new drug application (sNDA) for zanubrutinib (Brukinska) as a treatment option for adults with marginal zone lymphoma who have previously received at least 1 anti-CD20–based therapy.

Zanubrutinib is a potent, highly specific, and irreversible next-generation Bruton tyrosine kinase (BTK) inhibitor that was developed to maximize BTK occupancy and minimize off-target inhibition of TEC- and EGFR-family kinases, which are believed to be associated with atrial fibrillation, thrombocytopenia, and bleeding events.

Zanubrutinib is currently approved for the treatment of patients with mantle cell lymphoma (MCL) who have previously received at least 1 therapy. In February, the FDA accepted a sNDA for zanubrutinib as a treatment for adults with Waldenström macroglobulinemia; the Prescription Drug User Fee Act (PDUFA) is October 18, 2021.

The PDUFA date for the MZL indication is September 19, 2021.

The application includes data from the phase 2 MAGNOLIA trial which were presented during the 2020 ASH Annual Meeting. Initial results from the single-arm, open-label study showed that zanubrutinib was generally well tolerated among older, high-risk MZL patients who had received at least 1 prior line of an anti-CD20 treatment. The trial’s 68 patients, with an average age of 70 years, had a median of 2 prior treatments; more than 30% had refractory disease and nearly 40% had nodal MZL

Data were cut off on August 14, 2020. With a median time of 10.7 months, 66 patients were eligible to be evaluated for the drug’s efficacy. Results showed:

• The ORR was 74.2% (95% CI, 62.0-84.2), with 16 complete responses (24.2%), and 33 partial responses (50.0%).
• The ORR was strong across high-risk subgroups, including patients who were at least 75 years of age, who had an ORR of 88.9%; those with refractory disease, whose ORR was 71.0%, and those with nodal MZL, whose ORR was 84.0%.
• Median follow-up time for progression-free survival (PFS) was 9.13 months; PFS at 6 months was 80.0%, and 67.0% at 9 months.

Data from a global phase 1/2 trial which examined zanubrutinib in patients with B-cell malignancies, and pooled safety findings from 847 patients with B-cell malignancies who received the BTK inhibitor in 7 clinical trials, were also used to support the sNDA.

Jane Huang, MD, chief medical officer of Hematology at the drug's developer, BeiGene, said in a statement that MZL is a serious disease that affects more than 2000 patients a year in the United States, and that zanubrutinib would provide them with a new treatment option.