FDA Accepts New Drug Application for Zanubrutinib Combination for R/R Follicular Lymphoma


Zanubrutinib combined with obinutuzumab was previously granted both Fast Track and Orphan drug designations for patients with relapsed or refractory follicular lymphoma.

BeiGene announced that the FDAhas accepted a supplemental new drug application (sNDA) for zanubrutinib (Brukinsa) plus obinutuzumab (Gazyva) for patients with relapsed or refractory (R/R) follicular lymphoma (FL). Zanubrutinib is a small molecule Bruton’s tyrosine kinase (BTK) inhibitor currently being evaluated as a monotherapy and combination therapy in more than 30 trials worldwide. It was designed to continuously inhibit BTK and treat B-cell malignancies by optimizing bioavailability and selectivity.

Burkitt's lymphoma cells, a cancer of the lymphatic system, monoclonal B-cell tumor, 3D illustration | Image credit: Dr_ Microbe - stock.adobe.com

Lymphoma cells | Image credit: Dr_ Microbe - stock.adobe.com

“[FL] is the most common slow-growing non-Hodgkin lymphoma, but there are limited treatment options for patients whose condition has progressed after two lines of therapy. We are therefore pleased that Brukinsa is the first [BTK] inhibitor to demonstrate efficacy in follicular lymphoma and plan to continue worldwide regulatory submissions based on the ROSEWOOD results,” said Mehrdad Mobasher, MD, MPH, Beigene chief medical officer, Hematology, in a press release.

The filing of the sNDA was based on findings from the phase 2 ROSEWOOD study (NCT03332017). The study enrolled 217 patients who were previously treated for R/R non-Hodgkin lymphoma with 2 or more lines of therapy. Out of the 217 patients, 145 were administered zanubrutinib with obinutuzumab and the other 72 patients received obinutuzumab monotherapy. Zanubrutinib plus obinutuzumab produced a better outcome than obinutuzumab monotherapy, with a 68.3% overall response rate (ORR) compared with 45.8% with monotherapy (p = 0.0017). The responses produced by the combination were durable, with an 18-month landmark duration of response of 69.3%, according to the study.

“Because new BTK is continuously synthesized, Brukinsa was specifically designed to deliver complete and sustained inhibition of the BTK protein by optimizing bioavailability, half-life, and selectivity. With differentiated pharmacokinetics compared to other approved BTK inhibitors, Brukinsa has been demonstrated to inhibit the proliferation of malignant B cells within a number of disease relevant tissues,” Beigene said in the press release.

The sNDA also included longer-term data showing that the efficacy benefit for the combination was maintained at a median follow-up of 20.2 months, with an ORR of 69.0% compared with 45.8% for obinutuzumab monotherapy (p = 0.0012). Further, the combination lowered the risk of disease progression or death by 50% vs obinutuzumab monotherapy (HR 0.50; 95% CI 0.33-0.75).

Safety findings from the ROSEWOOD study mirrored what was previously found in trials for zanubrutinib plus obinutuzumab. The most common treatment-emergent adverse events in the combination arm vs the obinutuzumab monotherapy arm were diarrhea (18.2% vs 16.9%), fatigue (15.4% vs 14.1%), and pyrexia (13.3% vs 19.7%).

Other warnings and precautions include hemorrhaging, infections, cytopenia, second primary malignancies, cardiac arrhythmias, embryo-fetal toxicity, and adverse reactions.

Zanubrutinib was previously granted accelerated approval for the treatment of adult patients with mantle cell lymphoma (MCL) who have already had 1 prior therapy. It is also indicated for adult patients with chronic lymphocytic leukemia or small lymphocytic lymphoma, Waldenström’s macroglobulinemia, and R/R marginal zone lymphoma who have received at least 1 anti-CD20-based regimen.


BeiGene Announces FDA Acceptance of sNDA for Fifth BRUKINSA® Indication. News release. BeiGene. July 12, 2023. Accessed July 14, 2023. https://ir.beigene.com/news/beigene-announces-fda-acceptance-of-snda-for-fifth-brukinsa-indication/5e78f817-3655-4679-ab15-45715fddf585/.

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