BeiGene’s Phase III Trial of Zanubrutinib Misses Late-Stage Goals in Waldenström’s Macroglobulinemia

Beigene announced that its Phase III Trial of zanubrutinib compared to Johnson & Johnson/AbbVie’s ibrutinib did not achieve statistical significance for its primary endpoint. While zanubrutinib failed to achieve superiority in complete response (CR) and very good partial response (VGPR) rates for zanubrutinib compared to ibrutinib, it did demonstrate a higher VGPR rate as well as improvements in safety and tolerability in this first randomized comparative trial for the investigational small molecule Bruton’s tyrosine kinase (BTK) inhibitor.

The ASPEN trial was a randomized Phase III trial of 229 patients with Waldenström’s Macroglobulinemia (WM), a currently incurable version of non-Hodgkin’s lymphoma. It was conducted in 61 centers across Europe, Australia, and the US. There were two cohorts in the study: a randomized cohort of patients with a MYD88 mutation and a non-randomized cohort of patients with MYD88 wild-type (MYD88WT). Historically, MYD88WT patients have responded poorly to ibrutinib therapy. The MYD88WT cohort showed an overall response rate (ORR) of 80.8%, a major response rate (MRR; partial response or better) of 53.8%, and a VGPR rate of 23.1%. In the overall patient population, the VGPR rate as 28.4% in the zanubrutinib arm and 19.2% in the ibrutinib arm, indicating that there was not a statistically significant difference.

There are numerous other ongoing clinical trials involving zanubrutinib for chronic lymphocytic leukemia (CLL) and other lymphomas. GlobalData expects Beigene to continue to pursue approval for zanubrutinib therapy in the treatment of patients with WM and to continue trialing zanubrutinib against its competitors, Johnson & Johnson’s ibrutinib or Roche’s Rituxan (rituximab).