Policy & Regulation
Health Canada Approves Brukinsa for the Treatment of Waldenström's Macroglobulinemia
4 March 2021 - - Chinese commercial-stage biotechnology company BeiGene, Ltd's (NASDAQ: BGNE) (HKEX: 06160) Brukinsa (zanubrutinib) has been approved by Health Canada for the treatment of adult patients with Waldenström's macroglobulinemia.

Following the previously granted priority review in September 2020, the Health Canada approval for Brukinsa is based on efficacy results from the ASPEN clinical trial, a Phase 3 randomized, open-label, multicenter trial (NCT03053440) that evaluated Brukinsa compared to ibrutinib in patients with relapsed/refractory or treatment-naïve WM who harbor a MYD88 mutation (MYD88MUT).

In the ASPEN trial, Brukinsa demonstrated numerically higher very good partial response rate and a favorable safety profile over ibrutinib, although the primary endpoint of statistical superiority related to deep response (VGPR or better) was not met.

As assessed by independent review committee per adaptation of the response criteria updated at the Sixth International Workshop on Waldenström's Macroglobulinemia, the combined complete response + VGPR rate in the overall intention-to-treat population was 28.4% with Brukinsa (95% CI:20, 38), compared to 19.2% with ibrutinib (95% CI: 12, 28).

In the ASPEN trial, of the 101 patients with WM randomized and treated with Brukinsa, 4% of patients discontinued due to adverse events, including cardiomegaly, neutropenia, plasma cell myeloma, and subdural hemorrhage.

Adverse events leading to dose reduction occurred in 14% of patients, with the most common being neutropenia and diarrhea.

The overall safety profile of Brukinsa is based on pooled data from 779 patients with B-cell malignancies treated with Brukinsa in clinical trials.

The most common adverse reactions with Brukinsa were neutropenia, thrombocytopenia, upper respiratory tract infection, anemia, rash, musculoskeletal pain, diarrhea, cough, contusion, pneumonia (grouped terms), urinary tract infection, hemorrhage (grouped terms), and hematuria.

The most frequent serious adverse reactions were pneumonia (10.0%) and hemorrhage.

The recommended total daily dose of Brukinsa is 320mg. Brukinsa is expected to be available in Canada in the coming weeks.

Waldenström's macroglobulinemia (WM) is a rare indolent B-cell lymphoma that occurs in less than 2% of patients with non-Hodgkin's lymphoma.

The disease usually affects older adults and is primarily found in the bone marrow, although lymph nodes and the spleen may be involved.

In Canada and the United States, the incidence rate of WM is about five cases per m people per year.

The Phase 3 randomized, open-label, multicenter ASPEN clinical trial (NCT03053440) evaluated zanubrutinib versus ibrutinib in people with relapsed/refractory or treatment-naïve Waldenström's macroglobulinemia.

The primary objective was to establish superiority of zanubrutinib compared to ibrutinib as demonstrated by the proportion of people achieving complete response or very good partial response.

Secondary endpoints included major response rate, duration of response and progression-free survival, and safety, measured by incidence, timing and severity of treatment-emergent adverse events.

The pre-specified analysis populations for the trial included the overall population (n=201) and R/R patients (n=164). Exploratory endpoints included quality of life measures.

The study includes two cohorts, a randomized cohort (cohort 1) consisting of 201 patients with a MYD88 mutation and a non-randomized cohort (cohort 2) in which 28 patients with MYD88 wild-type (MYD88WT) received zanubrutinib because they have historically responded poorly to ibrutinib therapy.

The randomized cohort 1 enrolled 102 patients (including 83 relapsed or refractory patients and 19 treatment-naïve patients) in the zanubrutinib arm and 99 patients (including 81 R/R patients and 18 TN patients) in the ibrutinib arm.

Patients in the zanubrutinib arm were assigned to receive zanubrutinib 160 mg twice daily and patients in the ibrutinib arm received 420 mg of ibrutinib once daily.

Results of cohort 2 were previously presented at the 24th Congress of European Hematology Association and showed an overall response rate of 80.8%, a major response rate (MRR; partial response or better) of 53.8% and a VGPR rate of 23.1%.

Brukinsa (zanubrutinib) is a small molecule inhibitor of Bruton's tyrosine kinase, discovered by BeiGene scientists, that is currently being evaluated globally in a broad pivotal clinical program as a monotherapy and in combination with other therapies to treat various B-cell malignancies.

Brukinsa is a kinase inhibitor indicated for the treatment of adult patients with mantle cell lymphoma who have received at least one prior therapy.

This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

BeiGene is a global, commercial-stage biotechnology company focused on discovering, developing, manufacturing, and commercializing innovative medicines to improve treatment outcomes and access for patients worldwide.

It currently market two internally discovered oncology medicines: BTK inhibitor Brukinsa (zanubrutinib) in the United States and China, and anti-PD-1 antibody tislelizumab in China.
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