BASEL, Switzerland & CAMBRIDGE, Mass.--(BUSINESS WIRE)--BeiGene (NASDAQ: BGNE; HKEX: 06160) announced today that the United Kingdom (UK) Medicines and Healthcare products Regulatory Agency (MHRA) has granted a marketing authorisation for BRUKINSA® (zanubrutinib) in Great Britain, for the treatment of eligible adult patients with Waldenström’s macroglobulinemia (WM) who have received at least one prior therapy or for the first-line treatment of eligible patients unsuitable for chemo-immunotherapy.
“BRUKINSA is a highly selective BTK inhibitor which, in clinical studies, has provided meaningful improvements in tolerability for some patients with WM compared to ibrutinib,” said Dr. Roger Owen, Consultant Haematologist at St. James University Hospital Institute of Oncology in Leeds, UK, and a principal investigator of the ASPEN trial. “Today’s authorisation of BRUKINSA will soon allow eligible patients in Great Britain to access an important new treatment option that may offer improved outcomes.”
Although the primary endpoint of statistical superiority related to deep response, very good partial response (VGPR) or better, was not met in the Phase 3 ASPEN trial, BRUKINSA demonstrated a higher VGPR rate – 28% (29/102) compared to 19% in ibrutinib (19/99).1 In addition, 94% of patients on BRUKINSA (n=102) continued to respond for a year or longer compared with 88% of patients on ibrutinib (n=99) who continued to respond for a year or longer.1 Additionally, compared to ibrutinib, BRUKINSA demonstrated a lower frequency of certain adverse events, including atrial fibrillation or flutter (2/101, 2.0% vs. 15/98, 15.3%), minor bleeding (49/101, 48.5% vs. 58/98, 59.2%), and major haemorrhage (6/101, 5.9% vs. 9/98, 9.2%).1 Read more about the ASPEN trial results.
“The authorisation of BRUKINSA in WM in Great Britain is a significant step forward in our commitment to making our BTK inhibitor accessible to eligible patients who may benefit,” said Dr. Jane Huang, Chief Medical Officer, Haematology at BeiGene. “BRUKINSA was designed to completely block BTK and stop growth signalling to cancerous B cells, and has demonstrated efficacy and advantages in tolerability over ibrutinib in the ASPEN trial, and we believe it will become a widely-considered treatment option for eligible patients with WM.”
“As we continue to work towards having a lasting impact in the global fight against cancer, the authorisation of BRUKINSA in Great Britain is a great step forward in making a difference in the lives of eligible patients,” added Dr. Robert Mulrooney, General Manager, UK & Ireland at BeiGene. “This is an exciting milestone as BeiGene continues our focus on increasing global access to innovative oncology medicines.”
About Waldenström’s Macroglobulinemia
Waldenström’s macroglobulinemia (WM) is a generally indolent and relatively rare B-cell malignancy characterized by bone marrow infiltration with monoclonal immunoglobulin M (IgM) secreting lymphoplasmacytic cells. WM represents less than two percent of all non-Hodgkin’s lymphomas and typically progresses slowly after diagnosis.3 The disease usually affects older adults and is primarily found in the bone marrow, although lymph nodes and the spleen may be involved.3
About the ASPEN trial
The Phase 3 randomized, open-label, multicentre ASPEN clinical trial (NCT03053440) evaluated BRUKINSA (zanubrutinib) versus ibrutinib in patients with relapsed or refractory (R/R) WM or treatment-naïve (TN) WM considered unsuitable for treatment with chemoimmunotherapy. The primary objective was to establish superiority of BRUKINSA compared to ibrutinib as demonstrated by the proportion of patients achieving complete response (CR) or very good partial response (VGPR). Secondary endpoints included major response rate (MRR), duration of response (DoR) and progression-free survival (PFS), 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), of which the majority were R/R patients (n=164). Exploratory endpoints included quality of life measures.
As assessed by an independent review committee (IRC) based on the modified Sixth International Workshop on Waldenström’s Macroglobulinemia (IWWM-6) response criteria (Treon 2015), the combined rate of CR and VGPR in the overall intention-to-treat (ITT) population was 29% with BRUKINSA (95% CI: 20, 38), compared to 19% with ibrutinib (95% CI: 12, 28). While this difference was not statistically significant, BRUKINSA did achieve numerically higher VGPR rates.1
In the ASPEN trial, BRUKINSA demonstrated a lower frequency of adverse reactions that have raised concern with BTK inhibitors, including atrial fibrillation or flutter (2% vs. 15%), minor bleeding (49% vs. 59%) and major haemorrhage (6% vs. 9%) compared to ibrutinib. Despite higher rates of grade ≥3 neutropenia, patients on BRUKINSA did not demonstrate higher rates of infection as compared to those receiving ibrutinib. Of the 101 eligible patients with WM treated with BRUKINSA, 4% (4/101) of patients discontinued due to adverse events, and adverse events leading to dose reduction occurred in 14% (14/101) of patients.1
The study includes three arms in two cohorts, a randomized cohort (Cohort 1, N=201) consisting of patients with a MYD88 mutation (MYD88MUT) and a non-randomized cohort (Cohort 2, N=28) in which patients with MYD88 wild type (MYD88WT) received BRUKINSA because historic data indicated they were unlikely to benefit from ibrutinib. The randomized Cohort 1 enrolled 102 patients (including 83 R/R patients and 19 TN patients) in the BRUKINSA arm and 99 patients (including 81 R/R patients and 18 TN patients) in the ibrutinib arm. Patients in the BRUKINSA arm were assigned to receive BRUKINSA 160 mg twice daily (BID) and patients in the ibrutinib arm received 420 mg of ibrutinib once daily (QD).
About BRUKINSA
BRUKINSA (zanubrutinib) 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 agents to treat various B-cell malignancies. Because new BTK is continuously synthesized, BRUKINSA was specifically designed to deliver 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.2
Safety Information
The most commonly occurring adverse reactions (≥20%) were neutropenia (56.2%), thrombocytopenia (45.1%), upper respiratory tract infection (44.3%), haemorrhage/haematoma (32.2%), rash (29.8%), bruising (29.1%), anemia (28.9%), musculoskeletal pain (24.3%), diarrhea (23.6%), pneumonia (22.1%), and cough (21.7%).
The most common Grade 3 or higher adverse reactions (>5%) were neutropenia (28.0%), pneumonia (11.6%), thrombocytopenia (11.4%), and anemia (6.9%).
Of the 779 patients treated with zanubrutinib, 3.6% of patients discontinued treatment due to adverse reactions. The most frequent adverse reaction leading to treatment discontinuation was pneumonia (1.8%). Adverse reaction leading to dose reduction occurred in 4.9% of patients.
The recommended total daily dose of zanubrutinib is 320 mg. The daily dose may be taken either once daily (four 80 mg capsules) or divided into two doses of 160 mg twice daily (two 80 mg capsules).
BeiGene Oncology
BeiGene is committed to advancing best and first-in-class clinical candidates internally or with like-minded partners to develop impactful and affordable medicines for patients across the globe. We have a growing R&D team of approximately 2,750 colleagues dedicated to advancing more than 90 ongoing or planned clinical trials that have involved more than 14,000 patients and healthy volunteers. Our expansive portfolio is directed predominantly by our internal colleagues supporting clinical trials in more than 45 countries and regions. Haematology-oncology and solid tumour targeted therapies and immuno-oncology are key focus areas for the Company, with both mono- and combination therapies prioritized in our research and development. BeiGene currently has three approved medicines discovered and developed in our own labs: BTK inhibitor BRUKINSA in the United States, China, the EU, Canada, Australia, the United Kingdom and additional international markets; and the non-FC-gamma receptor binding anti-PD-1 antibody tislelizumab as well as the PARP inhibitor pamiparib in China.
BeiGene also partners with innovative companies who share our goal of developing therapies to address global health needs. We commercialize a range of oncology medicines in China licensed from Amgen and Bristol Myers Squibb. We also plan to address greater areas of unmet need globally through our collaborations including with Amgen, Bio-Thera, EUSA Pharma, Mirati Therapeutics, Seagen, and Zymeworks. BeiGene has also entered into a collaboration with Novartis granting Novartis rights to develop, manufacture, and commercialize tislelizumab in North America, Europe, and Japan.
About BeiGene
BeiGene is a global, science-driven biotechnology company focused on developing innovative and affordable medicines to improve treatment outcomes and access for patients worldwide. With a broad portfolio of more than 40 clinical candidates, we are expediting development of our diverse pipeline of novel therapeutics through our own capabilities and collaborations. We are committed to radically improving access to medicines for two billion more people by 2030. BeiGene has a growing global team of over 7,700 colleagues across five continents. To learn more about BeiGene, please visit www.beigene.com and follow us on Twitter at @BeiGeneGlobal.
Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 and other federal securities laws, including statements regarding the planned commercialization and market access of BRUKINSA in the United Kingdom and additional development, regulatory filings and potential approvals in other markets, provide improved clinical benefits with advantages in safety, the potential for BRUKINSA to become the preferred treatment option among patients with WM and their physicians, the potential commercial opportunity for BRUKINSA, and BeiGene’s plans, commitments, aspirations and goals under the headings “BeiGene Oncology” and “About BeiGene”. Actual results may differ materially from those indicated in the forward-looking statements as a result of various important factors, including BeiGene's ability to demonstrate the efficacy and safety of its drug candidates; the clinical results for its drug candidates, which may not support further development or marketing approval; actions of regulatory agencies, which may affect the initiation, timing and progress of clinical trials and marketing approval; BeiGene's ability to achieve commercial success for its marketed medicines and drug candidates, if approved; BeiGene's ability to obtain and maintain protection of intellectual property for its medicines and technology; BeiGene's reliance on third parties to conduct drug development, manufacturing and other services; BeiGene’s limited experience in obtaining regulatory approvals and commercializing pharmaceutical products and its ability to obtain additional funding for operations and to complete the development and commercialization of its drug candidates and achieve and maintain profitability; the impact of the COVID-19 pandemic on the Company’s clinical development, regulatory, commercial and other operations, as well as those risks more fully discussed in the section entitled “Risk Factors” in BeiGene’s most recent quarterly report on Form 10-Q, as well as discussions of potential risks, uncertainties, and other important factors in BeiGene's subsequent filings with the U.S. Securities and Exchange Commission. All information in this press release is as of the date of this press release, and BeiGene undertakes no duty to update such information unless required by law.
References:
- Tam, et al. A randomized phase 3 trial of zanubrutinib vs ibrutinib in symptomatic Waldenström macroglobulinemia: the ASPEN study. Blood. October 2020. 136(18): 2038-2050.
- BRUKINSA. Package insert. BeiGene, Ltd; 20211. BRUKINSA. Package insert. BeiGene, Ltd; 2021
- Lymphoma Research Foundation. Available at https://lymphoma.org/aboutlymphoma/nhl/wm/. Accessed December 2020.
