Rare Daily Staff

The U.S. Food and Drug Administration approved BeiGene’s Brunkinsa for the treatment of adult patients with Waldenström’s macroglobulinemia, a rare lymphoma.

Waldenström macroglobulinemia (WM) is a malignant disorder of the bone marrow and lymphatic tissues, characterized by the presence of abnormally large numbers of B lymphocytes. As these cells accumulate in the body, excessive quantities of an antibody protein known as IgM are produced, causing the blood to become thick and affecting the flow of blood through smaller blood vessels. Small blood vessels may tear leading to bleeding in the nose, gums, or retina. The incidence of WMG is estimated to be about 5 per 1,000,000 people over the age of 50.

“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,” said Pete DeNardis, chair of the board at the International Waldenström’s Macroglobulinemia Foundation. “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.”

Brukinsa (zanubrutinib) is a small molecule inhibitor of Bruton’s tyrosine kinase (BTK) discovered by BeiGene scientists that is currently being evaluated globally in a broad clinical program as a monotherapy and in combination with other therapies to treat various B-cell malignancies. 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. Brukinsa has been demonstrated to inhibit the proliferation of malignant B cells within many disease relevant tissues.

The FDA’s approval of Brukinsa in WM is primarily based on efficacy results from the multicenter, open-label Phase 3 ASPEN trial comparing Brukinsa to ibrutinib in patients with WM. A total of 201 patients with a MYD88 mutation were enrolled in the randomized Cohort 1.

The primary efficacy endpoint of the ASPEN trial was very good partial response (VGPR) rate in the overall intention-to-treat (ITT) population as assessed by the independent review committee (IRC). Based on the modified Sixth International Workshop on Waldenström’s Macroglobulinemia (IWWM-6) response criteria, the VGPR rate was 28 percent with Brukinsa, compared to 19 percent with ibrutinib; based on the IWWM-6 response criteria, the VGPR rate was 16 percent with Brukinsa, compared to 7 percent with ibrutinib.

In the FDA-approved label, the major efficacy outcome is defined as response rate of partial response (PR) or better as assessed by IRC. Based on either IWWM-6 response criteria, the response rate was 78 percent with Brukinsa compared to 78 percnet with ibrutinib, and the event-free duration of response at 12 months was 94 percent with Brukinsa, compared to 88 percent with ibrutinib.

The most common (≥20 percent) adverse reactions based on the pooled safety population of 779 patients were decreased neutrophil count, upper respiratory tract infection, decreased platelet count, rash, hemorrhage, musculoskeletal pain, decreased hemoglobin, bruising, diarrhea, pneumonia, and cough.

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