The FDA has approved zanubrutinib (Brukinsa) for the treatment of adult patients with Waldenström's macroglobulinemia, providing a new therapeutic option for this rare type of lymphoma. The approval represents the second therapy specifically approved for Waldenström's macroglobulinemia and marks zanubrutinib's second indication in the United States.
Clinical Trial Evidence
The approval was based on results from the phase 3 ASPEN trial (NCT03053440), a multicenter, open-label study that enrolled and randomized 201 patients with MYD88-mutant Waldenström's macroglobulinemia. The trial compared the efficacy of zanubrutinib versus ibrutinib (Imbruvica) in this patient population.
The study's primary efficacy endpoint was very good partial response (VGPR) in the overall intent-to-treat population. While not statistically significant, zanubrutinib demonstrated a higher VGPR rate of 28% compared to 19% with ibrutinib (P = 0.09). By International Workshop for Waldenström's Macroglobulinemia (IWWM) criteria, the VGPR rate was 16% versus 7% in the two arms, respectively.
Both treatments showed similar overall response rates based on IWMM-6 criteria, with zanubrutinib achieving a response rate of 78% (95% CI, 68%-85%) compared to 78% with ibrutinib (95% CI, 68%-86%). The 12-month event-free duration of response was 94% (95% CI, 86%-98%) with zanubrutinib compared to 88% (95% CI, 77%-94%) in the ibrutinib arm.
Improved Safety Profile
"The ASPEN trial provided compelling evidence that Brukinsa is a highly active BTK inhibitor in Waldenström's macroglobulinemia, and compared to the first-generation BTK inhibitor, showed improved tolerability across a number of clinically important side effects," said Steven Treon, MD, PhD, director of the Bing Center for Waldenström's Macroglobulinemia Research at the Dana-Farber Cancer Institute and Professor of Medicine at Harvard Medical School.
Common adverse effects observed with zanubrutinib included decreased neutrophil count, upper respiratory tract infection, decreased platelet count, rash, hemorrhage, musculoskeletal pain, decreased hemoglobin, bruising, diarrhea, pneumonia, and cough.
Treatment Administration
The recommended dose for zanubrutinib in patients with Waldenström's macroglobulinemia is either 160 mg twice daily or 320 mg once daily. The dose may be adjusted for adverse reactions and reduced for individuals who experience certain drug interactions or severe hepatic impairment.
Clinical Significance
Zanubrutinib is designed to deliver complete and sustained inhibition of the Bruton's tyrosine kinase (BTK) protein and can be used as monotherapy or in combination with other therapies to treat various B-cell malignancies. The drug has previously been approved for mantle cell lymphoma and chronic lymphocytic leukemia.
"We are delighted by today's FDA approval for Brukinsa in its second indication, offering a new treatment option with demonstrated efficacy and safety benefits for patients with Waldenström's macroglobulinemia," said Jane Huang, MD, chief medical officer of hematology at BeiGene. "As shown in the ASPEN trial, Brukinsa can improve treatment outcomes for these patients and potentially make a positive impact on their lives."
Pete DeNardis, chair of the board at the International Waldenström's Macroglobulinemia Foundation, emphasized the importance of expanded treatment options: "The approval of Brukinsa in Waldenström's macroglobulinemia, which is the second therapy approved specifically for the treatment of this rare type of lymphoma, is positive news for patients. Expanded treatment options offer new hope for those living with this disease and can potentially improve patient experience, especially oral therapies that can be given as a single agent."
