The FDA has approved zanubrutinib to treat adults with Waldenström’s macroglobulinemia (WM), according to a release from the manufacturer. 

Zanubrutinib is a small molecule BTK inhibitor. Unlike other medications in the same class, zanubrutinib “has been demonstrated to inhibit the proliferation of malignant B cells within a number of disease-relevant tissues,” according to the release.  

The FDA based the approval on results from the phase 3 ASPEN trial comparing zanubrutinib to ibrutinib in patients with WM. The first cohort of 201 patients were randomized 1:1 to receive 160 mg of zanubrutinib twice daily or 420 mg of ibrutinib once daily until disease progression or unacceptable toxicity. A second cohort of 26 patients with MYD88 wildtype mutation and 2 patients with MYD88 mutation unknown WM received 160 mg twice daily. 

The primary efficacy outcome was response rate, defined as partial response or better based on response criteria from the International Waldenström’s macroglobulinemia-6. The researchers also evaluated the duration of response as an efficacy outcome measure. The release noted that the response rate was 77.5% (95% CI, 68.1-85.1) in the zanubrutinib arm, which was similar to the ibrutinib arm. Event-free duration of response at 12 months was 94.4% (95% CI, 85.8-97.9) among patients treated with zanubrutinib compared with 88% (95% CI, 77- 94) among those treated with ibrutinib. In the second cohort, the overall response rate was 50% (95% CI, 29.9-70.1). 

“The ASPEN trial provided compelling evidence that [zanubrutinib] 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,” 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, said in a release from the manufacturer. 

The most common adverse reactions reported with zanubrutinib included decreased neutrophil count, upper respiratory tract infection, and decreased platelet count. 

The FDA release noted that zanubrutinib had previously been granted Fast Track and Orphan Drug designations.


Photo Credit: Getty Images