On December 9-11, the American Society of Hematology (ASH) Annual Meeting was successfully held, in which a total of 24 abstracts from BeiGene were included, including 3 oral presentations.
At the ASH meeting, BeiGene presented three key data presentations from zanubrutinib, including the results of a three-year follow-up period from the global Phase 3 head-to-head ALPINE study. The data showed that zanubrutinib showed sustained progression-free survival (PFS) superiority over ibrutinib at a median follow-up of 39 months in patients with *** or refractory chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL), with a 3-year PFS rate of 649% and 548%（hr: 0.68; p=0.0011）。
The extended follow-up of the ALPINE study suggests that the 3-year OS rate in the zanubrutinib group was higher than that in the control group. The 3-year OS rate was 82 in the zanubrutinib and ibrutinib groups, respectively5% and 796%, and zanubrutinib showed a trend towards potentially better OS, with fewer deaths in the zanubrutinib group (HR: 0.).75; p=0.098）。In addition, zanubrutinib continues to demonstrate a more favorable safety profile and tolerability compared to ibrutinib.
Thanks to advances in the best approach, the overall survival (OS) of patients with CLL is generally longer, so PFS has become the "gold standard" in clinical trials, and OS itself is not the primary endpoint. After a follow-up period of more than 3 years, the alpine data once again demonstrated that zanubrutinib has better efficacy and a more favorable safety profile than ibrutinib. With positive data from two global Phase 3 clinical trials, including the ALPINE study, the U.S. FDA has fully approved zanubrutinib for patients with cll SLL.
Based on its excellent and durable safety and efficacy in head-to-head studies and other indications, zanubrutinib continues to deepen its global commercialization footprint, and has been approved in more than 65 international markets, making it the most approved BTK inhibitor in the most indications and with the widest layout. In the first three quarters of 2023, the total global sales of zanubrutinib totaled 8$7.7 billion, according to a third party**, zanubrutinib is expected to hit the new "$1 billion molecule" this year.
According to the company, BeiGene's current layout in the field of hematology has covered and expanded to include a variety of hematological malignancies such as CLL, acute myeloid leukemia, myelodysplastic syndrome, multiple myeloma, Richter transformation, and large B-cell lymphoma.
At this year's ASH conference, BeiGene also showcased the clinical progress of its core products, including the BCL-2 inhibitor Sonrotoclax and BTK CDAC BGB-16673, further strengthening the company's leading position in the field of hematology.
As a potential "best-in-class" BCL-2 inhibitor, Sonrotoclax has a shorter half-life and no drug accumulation than the marketed BCL-2 inhibitor venetoclax, which is expected to lead to a better safety profile. At present, Sonrotoclax has a wide clinical layout, with more than 600 patients enrolled in clinical trials, and has achieved differentiated efficacy and safety in multiple indications.
At this year's ASH Annual Meeting, Sonrotoclax presented three key data reports, ranging from monotherapy** to combination therapy, covering multiple indications for B-cell malignancies. Among them, sonrotoclax combined with zanubrutinib** showed encouraging clinical data in patients with CLL SLL. In an ongoing Phase 1 and 2 study, the combination was well tolerated with no cases of tumor lysis syndrome (TLS). The ** response rate reached 100%, including deep response. At follow-up, no patients experienced disease progression (100% PFS). BeiGene has initiated a Phase 3 registrational trial of the combination of sonrotoclax and zanubrutinib naïve CLL fixed-course therapy.
It is worth noting that at the ASH Annual Meeting, BeiGene presented for the first time data from the ongoing human trial of BTK CDAC BGB-16673, in which 128 patients have been enrolled, and the data are clinically significant, demonstrating a tolerable safety profile and significant clinical remission, which is expected to address the problem of BTK resistance. According to reports, BGB-16673, as a BTK degrader with the highest clinical progress, has a robust development plan, and BeiGene will accelerate the marketing, combination drug and phase 3 clinical trial process in 2024.