Zanubrutinib Surpasses Ibrutinib: A Case Study in Best-in-Class Innovation
BeOne Medicines is reshaping hematology with zanubrutinib. Superior efficacy, cleaner safety, and strong market momentum put it ahead of ibrutinib — a textbook case of best-in-class drugs eclipsing first-in-class pioneers.
Ibrutinib was first. Zanubrutinib is better.
In the battle against B-cell malignancies, BeOne Medicines (formally BeiGene) zanubrutinib (Brukinsa) has overtaken AbbVie/J&J’s pioneering ibrutinib (Imbruvica) as the Bruton’s tyrosine kinase (BTK) inhibitor of choice. With a 51% lower risk of disease progression [1], dramatically fewer cardiac side effects [2–3], and sales growth that outpaces all rivals [4–6], zanubrutinib is redefining standard of care in CLL, MCL, and beyond. Backed by the potent BCL-2 inhibitor sonrotoclax [7], BeOne Medicines is positioning itself as a global hematology leader — with China at the center.
Clinical Differentiation: Superiority Over Ibrutinib
Head-to-Head Trials
Zanubrutinib’s superiority over ibrutinib is established in randomized Phase III trials:
| Trial | Population | Endpoint | HR / Δ vs. Ibrutinib | Key Safety Finding |
|---|---|---|---|---|
| ALPINE | R/R CLL/SLL | PFS | HR 0.65 (p=0.0024) [1] | Atrial fibrillation: 2.5% vs. 10.1% [1] |
| ASPEN | WM | ORR / CR | CR 28% vs. 19% [2] | AF/flutter: 2% vs. 15% [2] |
| SEQUOIA | 1L CLL (del17p cohort) | PFS | 2-yr PFS 88% [3] | Consistent cardiac safety [3] |
| MCL pooled | R/R MCL | ORR | ORR 84% [8] | CR 68%, favorable tolerability [8] |
Takeaway: Zanubrutinib consistently shows equal or superior efficacy with markedly reduced cardiotoxicity.
Safety Advantage
- Atrial fibrillation/flutter: 3–5× lower than ibrutinib [1–2].
- Hypertension/bleeding: Significantly reduced [2–3].
- Discontinuations due to AE: Lower in zanubrutinib arms [1–3].
This safety edge has been decisive in physician adoption, especially in elderly patients.
Market Impact: Overtaking Ibrutinib
| Drug (Brand) | Manufacturer | 2022 Sales | 2023 Sales | 2024 Sales | Q2 2025 Run Rate | Trend / Notes |
|---|---|---|---|---|---|---|
| Ibrutinib (Imbruvica) | AbbVie / J&J | $4.6B [4] | $3.5B [5] | $2.4B [6] | $0.5B [6] | Steep decline (-47% YoY); Peak $8.7B 2021; FDA: 2013 (CLL/SLL, MCL), 2017 (WM), 2022 (cGVHD); EU: 2014–2015; China: 2017 [4–6,9–10] |
| Zanubrutinib (Brukinsa) | BeOne / BeiGene | $1.3B [4] | $2.1B [5] | $3.3B [6] | $1.1B [6] | Rapid growth (+55% YoY); Peak projected $5B; FDA: 2019 (MCL), 2023 (CLL/SLL, WM), 2024 (FL); China: 2020–2023; EU: 2021–2024 [4–6,9–10] |
| Acalabrutinib (Calquence) | AstraZeneca | $1.6B [4] | $2.0B [5] | $3.0B [6] | $0.8B [6] | Steady (+50% YoY); FDA: 2017–2022; China: 2021–2022; Peak ~$4B [4–6,9–10] |
| Pirtobrutinib (Jaypirca) | Eli Lilly | $0.3B [4] | $0.4B [5] | $0.34B [6] | $0.22B [6] | Emerging; FDA: 2023 (CLL/MCL); EU: 2023; Peak $4B projected [4–6,9–10] |
| Orelabrutinib (Obrutinib) | InnoCare | $0.14B [4] | $0.18B [5] | $0.14B [6] | $0.09B [6] | China-focused; China 2020–2021; Emerging global reach [4–6,9–10] |
Comment: Zanubrutinib overtook acalabrutinib in Q4 2024 ($0.83B vs. $0.81B) and is closing the gap with ibrutinib. China’s NRDL reimbursement and new formulations (film-coated tablets, 2025) have fueled adoption [6,15].
BeOne Medicines’ Vision Beyond Zanubrutinib
Following BeiGene’s restructuring in 2024, BeOne Medicines now houses zanubrutinib and a growing hematology pipeline:
| Candidate | Target | Stage | Highlight |
|---|---|---|---|
| Sonrotoclax | BCL-2 | Phase II (CLL, AML) | Higher selectivity than venetoclax; promising efficacy in combination with zanubrutinib [7,10] |
| BGB-16673 | BTK degrader | Phase I/II | Addresses BTKi-resistant mutations [11] |
| BGB-11417 | BCL-2 | Phase I/II | Backup with distinct PK/PD [12] |
| Next-gen BTKi combos | BTK + BCL-2 | Ongoing | Synergistic regimens under study [10–11] |
Strategic focus: Position as a “hematology pure-play” anchored in China but competing globally.
China’s Role in the BTK Story
- Clinical trials: China supplied ~40% of patients in pivotal zanubrutinib studies [1–3,8].
- Regulatory speed: NMPA approvals closely aligned with FDA/EMA [9].
- Market access: NRDL reimbursement has driven uptake across CLL, WM, and MCL [9].
- Deal flow: BeiGene’s spinout of BeOne reflects China’s strategy to build focused, globally competitive biotechs [13].
Global Adoption and Market Context
Beyond China, zanubrutinib has gained approvals in 75 markets, including the US (2019 MCL; 2023 CLL/SLL/WM), EU (2021 WM, 2022 CLL/MZL), and Japan (2022 CLL) [9,10]. Uptake in North America and Europe has accelerated, with H1 2025 sales of $0.68B in the US (+43% YoY) and $0.15B in the EU (+85% YoY) [8]. This shows zanubrutinib’s ability to compete globally, not just in China.
Conclusion: From First-in-Class to Best-in-Class
Zanubrutinib’s rise is more than just a single drug story. It is the clearest modern example of a best-in-class therapy eclipsing a first-in-class pioneer — a cycle seen across statins, GLP-1 agonists, and PD-1 inhibitors. With superior efficacy, improved safety, and commercial momentum, zanubrutinib has transformed BeOne into a serious global hematology competitor.
First-in-class drugs open the market. Best-in-class drugs win it.
In our next post [16], we’ll step back from BTK inhibitors to analyze this dynamic across therapeutic areas — and how China’s drugmakers are shaping the future of “best-in-class innovation.”
References
- Hillmen, P.; et al. N Engl J Med 2020, 383, 2016–2027.
- Tedeschi, A.; et al. Lancet Hematol 2021, 8, e362–e372.
- Tam, C. S.; et al. Blood 2021, 138, 328–338.
- EvaluatePharma World Preview 2025, BTK Inhibitors Market Report, 2025.
- Company Annual Reports: AbbVie, BeiGene, AstraZeneca, Eli Lilly, InnoCare, 2023.
- Company H1 2025 Financial Filings.
- BeOne Medicines, Clinical Pipeline Update, 2025.
- Dreyling, M.; et al. Haematologica 2022, 107, 1501–1512.
- FDA/EMA/NMPA Approval Databases.
- NCCN Guidelines: B-Cell Malignancies, Version 2025.
- BeOne Medicines Investor Presentation, Q2 2025.
- ClinicalTrials.gov: NCT05471843, NCT06742996.
- BeOne Medicines Corporate Strategy Report, 2024.
- ICML 2025 Abstracts on Zanubrutinib Real-World Data.
- Pricing & Reimbursement Analysis, China NRDL, 2025.
- SinoDrugWatch. Zanubrutinib Surpasses Ibrutinib: A Case Study in Best-in-Class Innovation. SinoDrugWatch.com, August 31, 2025.
Disclaimer: For informational purposes only. Data are based on publicly available sources, company filings, and scientific literature as of August 31, 2025. Readers should consult healthcare professionals and relevant journals for medical decisions, and independent financial advisors for investment guidance.