On December 13, 2022 BeiGene (NASDAQ: BGNE; HKEX: 06160; SSE: 688235) a global biotechnology company, reported the final progression-free survival (PFS) analysis of the ALPINE trial demonstrating superior efficacy and a favorable cardiac safety profile for patients receiving BRUKINSA as compared to IMBRUVICA in a global phase 3 trial in patients with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL) or small lymphocytic leukemia (SLL) (Press release, BeiGene, DEC 13, 2022, View Source [SID1234625394]). These data will be presented (Abstract #LBA-6) during the late-breaking session at the 64th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in New Orleans and simultaneously published in The New England Journal of Medicine. The paper’s lead author Jennifer Brown, M.D., Ph.D., Director, CLL Center at Dana-Farber Cancer Institute will present these data.

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Dr. Brown noted that "PFS is the gold standard for measuring efficacy in CLL clinical trials. The ALPINE data showing superior efficacy and consistent benefit across patient subgroups including patients with high-risk del(17p)/TP53, along with a favorable cardiovascular safety profile, provide compelling evidence for BRUKINSA as a practice-changing Bruton’s tyrosine kinase (BTK) inhibitor for patients with CLL."

"BRUKINSA was specifically designed to maximize BTK occupancy and minimize off-target effects. Our clinical development programs were intended to test for a differentiated efficacy and safety profile," said Mehrdad Mobasher, M.D., M.P.H., Chief Medical Officer, Hematology at BeiGene. "We believe the ALPINE PFS data and cardiac safety results for BRUKINSA, including an absence of cardiac death, demonstrate a meaningful advance in outcomes for patients with CLL."

In this final analysis, BRUKINSA achieved superior PFS over ibrutinib (HR: 0.65 [95% CI, 0.49-0.86] p=0.0024, for both Independent Review Committee [IRC] and investigator). At 24 months, the investigator-assessed PFS rates were 78.4% for BRUKINSA compared to 65.9% with ibrutinib. The PFS benefit was observed across all major subgroups, including high-risk del(17p)/TP53 (HR: 0.52; [95% CI, 0.30-0.88]), as assessed by IRC. BRUKINSA also demonstrated higher overall response rate (ORR), with a response rate of 80.4% versus 72.9% (two-sided p=0.0264), as assessed by IRC.

BRUKINSA was generally well-tolerated with fewer adverse events leading to treatment discontinuation compared with ibrutinib (15.4% vs. 22.2%). There was a lower rate of cardiac disorders for BRUKINSA compared with ibrutinib (21.3% vs 29.6%), and cardiac disorders leading to treatment discontinuation occurred in one BRUKINSA patient versus 14 ibrutinib patients (0.3% vs. 4.3%). No patient receiving BRUKINSA died due to a cardiac adverse event; six patients receiving ibrutinib experienced a fatal cardiac adverse event (0% vs. 1.9%). The most commonly reported treatment emergent adverse events (≥20%) with BRUKINSA and ibrutinib were diarrhea (16.0% vs. 24.1%), hypertension (14.8% vs. 11.1%), neutropenia (22.8% vs. 18.2%), COVID-19 (23.1% vs. 17.9%), and upper respiratory tract infection (21.0% vs. 14.2%).

CLL is the most common type of leukemia in adults, accounting for about one-quarter of new cases of leukemia in the United States.1 The condition is characterized by consecutive relapses, with response to therapy ultimately determining clinical benefit, including survival.

BeiGene’s sNDA for BRUKINSA in CLL is currently under review with the FDA and has a target action date of January 20, 2023.

Investor Events

•Tuesday, December 13, 2022 – BeiGene will host a webcast and conference call following the ALPINE late-breaker presentation at 2:00 p.m. CST. BeiGene senior management along with invited medical experts will review the presented data and join for a Q&A panel.
oDial in: 855-303-0072; Passcode: 306575

•Tuesday, December 13, 2022 – BeiGene will host a webcast in Chinese at 6:00 p.m. CST/December 14, 2022 8:00 a.m. China time to capture company presentations at ASH (Free ASH Whitepaper). BeiGene senior management will review highlights of the presented data.
oDial in: +86 10 8783 3177 or +86 10 5387 6330; Passcode: 03233799

These events can be accessed live from the Investors section of BeiGene’s website at View Source, View Source or View Source Archived replays will be posted for 90 days following both events.

About ALPINE

ALPINE is a randomized, global Phase 3 trial (NCT03734016) comparing BRUKINSA against ibrutinib in previously treated patients with relapsed or refractory chronic lymphocytic leukemia CLL or SLL. In the trial, a total of 652 patients across Europe (60%), the United States (17%), China (14%), New Zealand and Australia (9%) were randomized into two arms, with the first receiving BRUKINSA (160 mg orally twice daily) and the second receiving ibrutinib (420 mg orally once daily) until disease progression or unacceptable toxicity.

The primary endpoint of overall response rate (ORR), defined by pre-specified non-inferiority of BRUKINSA versus ibrutinib, was assessed by investigator and IRC using the modified 2008 iwCLL guidelines, with modification for treatment-related lymphocytosis for patients with CLL, and per Lugano Classification for non-Hodgkin’s lymphoma for patients with SLL. There was pre-specified hierarchical testing of non-inferiority followed by superiority in ORR as assessed by investigator and IRC. Key secondary endpoints include PFS and event rate of atrial fibrillation or flutter; other secondary endpoints include duration of response, overall survival, and incidence of adverse events.

Interim study results from ALPINE were published online in Journal of Clinical Oncology in November 2022 (DOI: 10.1200/JCO.22.00510).

About BRUKINSA

BRUKINSA is a small-molecule inhibitor of Bruton’s tyrosine kinase (BTK) discovered by BeiGene scientists that is currently being evaluated globally in a broad clinical program as a monotherapy and in combination with other therapies to treat various B-cell malignancies. BRUKINSA was specifically designed to deliver targeted and sustained inhibition of the BTK protein by optimizing bioavailability, half-life, and selectivity. With differentiated pharmacokinetics compared to other approved BTK inhibitors, BRUKINSA has been demonstrated to inhibit the proliferation of malignant B cells within a number of disease-relevant tissues.

BRUKINSA is supported by a broad clinical program which includes more than 4,700 subjects in 35 trials in more than 30 geographies. To date, BRUKINSA is approved in more than 60 markets, including the United States, China, the European Union, Great Britain, Canada, Australia, South Korea, Switzerland, and additional international markets.