Regulatory Decision Summary for Brukinsa

The purpose of this Supplement to a New Drug Submission (SNDS)-Comparative and Manufacturing (Comp/C&M) for Brukinsa (zanubrutinib), filed by BeiGene Switzerland GmbH, was to obtain market authorization pursuant to section C.08.004 of the Food and Drug Regulations for a new dosage form and strength: a 160 mg zanubrutinib tablet for immediate release. Upon review of the submitted data package, Health Canada authorized Brukinsa as filed.

Brukinsa is indicated for the treatment of several lymphoproliferative disorders, including Waldenström’s macroglobulinemia, mantle cell lymphoma, marginal zone lymphoma, chronic lymphocytic leukemia/small lymphocytic leukemia, and follicular lymphoma.

Brukinsa (zanubrutinib) is indicated for the treatment of a number of lymphoproliferative disorders, including Waldenström’s macroglobulinemia, mantle cell lymphoma, marginal zone lymphoma, chronic lymphocytic leukemia/small lymphocytic leukemia, and follicular lymphoma.

The purpose of this submission was to introduce a tablet formulation of zanubrutinib. The sponsor’s strategy was to bridge the safety and efficacy determined from studies conducted with the Brukinsa capsule formulation to the Brukinsa tablet formulation by demonstrating that the rate and extent of absorption of zanubrutinib after administration of Brukinsa capsules is equivalent to that after administration of Brukinsa tablets. The sponsor also determined the effect of food on the bioavailability of zanubrutinib from the Brukinsa tablet formulation.

The results from the bioavailability study (BGB-3111-114) met the comparative bioavailability standards as per the Health Canada guidance document: Conduct and Analysis of Comparative Bioavailability Studies (2023). As such, the rate and extent of absorption of zanubrutinib from the two treatments administered (2 × 80 mg capsules and 1 × 160 mg tablet) are considered equivalent under fasting conditions.

A comparison of Brukinsa tablets under fed versus fasting conditions (Study BGB-3111-115) demonstrated that administration of a 160 mg or 320 mg dose of Brukinsa tablets, respectively, following a high-fat meal resulted in increases in zanubrutinib AUCT and C_max relative to administration of a 160 mg or 320 mg dose of Brukinsa tablets, respectively, under fasted conditions.

A comparison of Brukinsa tablets administered under fed conditions versus Brukinsa capsules administered under fasting conditions demonstrated that administration of a 160 mg or 320 mg dose of Brukinsa tablets, respectively, following a high-fat meal resulted in increases in zanubrutinib AUCT and Cmax relative to administration of a 160 mg or 320 mg dose of Brukinsa capsules, respectively, under fasted conditions.

These results demonstrated that for the tablet formulation, there is a food effect on C_max at both doses (160 mg QD and 320 mg QD), and it is greater for the tablet formulation than the currently marketed capsule formulation, and more evident at 320 mg. However, as the C_max observed with the tablet formulation in the high-fat fed state at both doses is within the range of exposure-safety analysis population derived from patients treated with the capsule formulation for the five approved indications, the tablet formulation taken with a high-fat meal is expected to have a similar safety profile to that of the capsule formulation, and is considered to be acceptable and not clinically significant. There are no significant outstanding concerns or issues with regard to the design or conduct of Studies BGB-3111-114 and BGB-3111-115.

No significant quality issues were noted with respect to the new formulation during the review, thus a Notice of Compliance (NOC) was recommended by the Quality Division.

The Risk Management Plan (version 3.0) was deemed to be acceptable by the Marketed Pharmaceutical Bureau.

Overall, the benefit-risk-uncertainty profile for the use of Brukinsa tablets (160 mg) for the approved indications is favourable when used under the conditions of use recommended in the approved Product Monograph. Therefore, NOC was recommended.

For further details about Brukinsa, please refer to the Product Monograph, approved by Health Canada and available through the Drug Product Database.