- U.S. Food and Drug Administration (FDA) (http://dev-voice.ons.org/topic/us-food-and-drug-administration-fda)
- Oncology Drug Research (http://dev-voice.ons.org/topic/oncology-drug-research)
- Clinical Practice (http://dev-voice.ons.org/topic/clinical-practice)
- Patient Safety (http://dev-voice.ons.org/topic/patient-safety)
FDA Approves Zanubrutinib for Waldenström Macroglobulinemia
On August 31, 2021, the U.S. Food and Drug Administration (FDA) approved (https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-zanubrutinib-waldenstroms-macroglobulinemia) zanubrutinib (Brukinsa®) for adult patients with Waldenström macroglobulinemia (WM).
Zanubrutinib was investigated in a randomized, active control, open-label trial (ASPEN, NCT03053440) comparing zanubrutinib to ibrutinib in patients with MYD88 L265P variant (MYD88MUT) WM. Patients in cohort 1 (n = 201) were randomized (1:1) to receive zanubrutinib 160 mg twice daily or ibrutinib 420 mg once daily until disease progression or unacceptable toxicity. Cohort 2 enrolled patients with MYD88 wildtype (MYD88WT) or MYD88 variant unknown WM (n = 26 and n = 2, respectively) who received zanubrutinib 160 mg twice daily.
The major efficacy outcome was response rate, which was defined as partial response (PR) or better as assessed by an independent review committee based on standard consensus response criteria from the International Workshop on WM-6. An additional efficacy outcome measure was duration of response (DOR).
Approval was based on a noncomparative assessment of response and DOR from the zanubrutinib arms, which had a response rate (CR + VGPR + PR) of 77.5% (95% CI = 68.1, 85.1) and event-free DOR at 12 months of 94.4% (95% CI = 85.8, 97.9) in cohort 1. In cohort 2, response (CR + VGPR + PR) as assessed by infrared coagulation was seen in 50% (13 out of 26 response-evaluable patients; 95% CI = 29.9, 70.1).
The most common adverse reactions, including laboratory abnormalities, reported in 20% or more of the patients receiving zanubrutinib were decreased neutrophil count, upper respiratory tract infection, decreased platelet count, rash, hemorrhage, musculoskeletal pain, decreased hemoglobin, bruising, diarrhea, pneumonia, and cough.
The recommended zanubrutinib dosage is 160 mg orally twice daily or 320 mg orally once daily.
The review used the Assessment Aid (https://www.fda.gov/about-fda/oncology-center-excellence/assessment-aid), a voluntary submission from the applicant to facilitate FDA’s assessment.
FDA granted the application fast track designation and orphan designation. A description of FDA expedited programs is in the Guidance for IndustryꟷExpedited Programs for Serious ConditionsꟷDrugs and Biologics (https://www.fda.gov/regulatory-information/search-fda-guidance-documents/expedited-programs-serious-conditions-drugs-and-biologics).
Healthcare professionals should report all serious adverse events they suspect are associated with the use of any medicine and device to FDA’s MedWatch Reporting System (https://www.accessdata.fda.gov/scripts/medwatch/index.cfm) or by calling 800-FDA-1088.
For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate (https://www.fda.gov/about-fda/oncology-center-excellence/project-facilitate) at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov (mailto:OncProjectFacilitate@fda.hhs.gov).