BeiGene, manufacturer of Brukinsa® (zanubritinib), a drug approved for the treatment of relapsed, refractory mantle cell lymphoma in China and the United States, reported the results of a comparative trial with the drug ibrutinib from an interim analysis which confirms that Zanubrutinib has an improved safety profile and superior investigator assessed overall response in patients with relapsed, refractory chronic lymphocytic leukemia or small cell leukemia (CLL). In Russia, Brukinsa® (zanubritinib) is localized and represented by Nanolek, a BeiGene distribution partner. The drug under regulatory review for relapsed, refractory MCL in the Russian Federation with potential approval at the end of the 2021.

BeiGene announced significant positive interim results from the ALPINE, a Phase 3 trial comparing anubritinib to ibrutinib in patients with recurrent or refractory chronic lymphocytic leukemia or small lymphocyte lymphoma. The interim analysis is based on a follow-up of 415 of 652 patients, each of whom has participated in the trial for at least 12 months.

Brukinsa® (zanubrutinib) is under regulatory review for relapsed, refractory MCL in the Russian Federation with potential approval at the end of the 2021.

Under a strategic agreement signed in 2020, Brukinsa® is represented in Russia and the EEC by Nanolek, which has exclusive rights to distribution, promotion, pharmacovigilance, as well as secondary packaging and release control for the drug.

In the ALPINE study, in terms of the ORR (objective response rate) – an important indicator of efficacy for oncohematologists and the primary endpoint for the trial – zanubrutinib demonstrated superiority according to the investigator assessment of ORR compared to ibrutinib (p = 0.0006). •    As assessed by independent review committee (IRC), zanubrutinib achieved a numerically higher than but not statistically significant ORR compared to ibrutinib.

These results were reported in an oral presentation as part of the Presidential Symposium and featured during the congress press briefing at the 26th European Hematology Association 2021 (EHA2021) Virtual Congress, taking place virtually on June 9-17, 2021.

The data for the second key study endpoints – progression-free survival in 652 patients – was immature at the time of interim analysis. Formal analysis will be performed when the target number of events are reached. The PFS rate at 12 months was 94.9% in the Zanubrutinib arm, compared to 84.0% in the Ibrutinib arm.

The study also proved additional characterization of the safety of the drug. Compared to ibrutinib, zanubrutinib showed statistically significant lower risk of fibrillation, which is characterized by an irregular heartbeat and can lead to blood clots, stroke, heart failure, and other heart complications. So, consistent with previous clinical trials, Zanubrutinib consistently demonstrates a better safety profile compared to Ibrutinib.

This is the second head-to-head comparison between zanubrutinib and ibrutinib conducted by BeiGene in its Phase 3 trials program.

Jane Huang, MD, Chief Medical Offer of BeiGene’s Department of Hematology, commented on the results: “Interim results from this head-to-head trial demonstrated that as a selective inhibitor, zanubrutinib provides benefits for patients and decreases the level of cardiac arrhythmia compared to Ibrutinib. The data from this interim analysis, in addition to zanubrutinib’s extensive clinical testing program, provided us with important new information to support its benefit-risk profile.”

“By the end of 2021, Brukinsa® which is currently under regulatory review has the potential to be available in Russia for relapsed, refractory mantle cell lymphoma. Cooperation between BeiGene and Nanolek has made it possible to launch Russian localization of a new generation drug in the shortest possible time. The localization of the drug will be provided at the Nanolek plant in the Kirov region,” said Anton Prozumentov, Head of Specialized Medicines Division, Nanolek.

“This partnership with BeiGene kicks off the development of the company’s portfolio of oncological drugs here in Russia,” says Vladimir Khristenko, President of Nanolek. “We are delighted that Brukinsa is proving to be a drug with compelling efficacy and an excellent safety profile – this gives more hope to patients who are dealing with a difficult cancer diagnosis.”

About the drug

Brukinsa® (Zanubrutinib): A small molecule inhibitor of Bruton’s tyrosine kinase developed by scientists at BeiGene, which is currently being developed in clinical programs around the world as a monotherapy or in combination with other drugs for the treatment of malignant B lymphocyte tumors. Mantle cell lymphoma is a malignant tumor from B-lymphocytes, cells of the immune system. It is classified as a so-called non-Hodgkin’s lymphomas. This type of lymphoma is characterized by high aggressiveness, a short time to progression, and chemoresistance in the period of relapse. Most patients come to the attention of doctors already in the advanced stage of the disease. The estimated incidence of mantle cell lymphoma in the Russian Federation is about 1,030 new cases per year. Brukinsa® (zanubritinib) is currently successfully used in the United States, China, and Canada in the treatment of B-cell-derived lymphoma.

About the ALPINE trial

ALPINE is a Phase 3 randomized global trial (NCT03734016) that compares zanubrutinib and ibrutinib in previously treated patients with recurrent or refractory chronic lymphocytic leukemia (CLL) or small lymphocyte lymphoma (SLL).

In the study, 652 patients were randomized into 2 groups, the first receiving zanubrutinib (160 mg orally twice a day), the second receiving ibrutinib (420 mg orally once a day) until disease progression or unacceptable toxicity.

The primary objective response rate (ORR) analysiswas assessed by the researcher and an independent expert committee (IEC) using the modified 2008 iwCLL guidelines – with the modification of lymphocytosis associated with treatment in patients with CLL and the Lugano classification for non-Hodgkin’s lymphoma for patients with small lymphocytic lymphoma (SLL).

Hierarchical testing was applied to prove that the drug was not inferior to the control drug in terms of efficacy and, according to the assessment of the researcher and the IEC, was superior to it in in terms of the objective response rate.

Key secondary endpoints include progression-free survival (PFS), duration of response, overall survival, and incidence of adverse events. Research is ongoing, with pre-defined ORR and CAP endpoints to be assessed in a final analysis expected in 2022.

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 committed to expediting the development of our diverse pipeline of novel therapeutics through collaborations or our own internal capabilities, with the aspirational goal of radically improving access to medicines for two billion more people by 2030. BeiGene is a headquarter-less company by design, with a growing global team of approximately 6,000 colleagues across five continents. To learn more about BeiGene, please visit www.beigene.com.

About Nanolek

Nanolek is a modern biopharmaceutical company and one of the leading producers of pediatric vaccines in Russia. Founded in 2011 by Vladimir Khristenko and Mikhail Nekrasov. It specializes in the production of import-substituting and innovative medicines, including in-house developments and those created in collaboration with international partners. In addition to vaccines, the portfolio includes drugs for the treatment of HIV, cancer and rare diseases.