FDA Grants Breakthrough Designation to Mantle Cell Lymphoma Treatment

BeiGene’s investigational Bruton’s tyrosine kinase (BTK) inhibitor, zanubrutinib (BGB-3111), has been granted Breakthrough Therapy designation by the FDA for the treatment of adults with mantle cell lymphoma (MCL) who have received at least 1 prior therapy, according to a company press release.¹

MCL is an aggressive form of non-Hodgkin lymphoma (NHL) that arises from B-cells originating in the “mantle zone,” according to BeiGene. Approximately 70,800 new cases of NHL were estimated in the United States in 2014, with MCL accounting for approximately 6%.¹

The designation is based on data presented at the 60^th Annual Meeting of the American Society of Hematology, which took place December 1-4, 2018. Results from the phase 2 trial of zanubrutinib in Chinese patients with relapsed or refractory MCL demonstrated a high rate of complete responses characterized by positron emission tomography-based imaging. For the study, patients were treated with zanubrutinib, dosed at 160 mg orally twice-daily.

Key findings include²:

• The overall response rate was 83.5%, the complete response rate was 58.8%, and the partial response rate was 24.7% for zanubrutinib.
• The 24-week progression-free survival was estimated at 82%.
• With 24.1 weeks median follow-up, the median duration of response had not yet been reached and 90% of responders were still in response at 24 weeks.

Additionally, zanubrutinib demonstrated tolerability that was consistent with previous reports in patients with B-cell malignancies. The most common adverse events reported were decreased neutrophil count (31.4%), rash (29.1%), upper respiratory tract infection (29.1%), and decreased platelet count (22.1%).²

In a global phase 1 trial, zanubrutinib was evaluated as a monotherapy in patients with different subtypes of B-cell malignancies, including MCL. The data showed consistent outcomes for patients outside of China.²

Clinical trials are also investigating the use of zanubrutinib in Waldenström macroglobulinemia (WM), previously untreated chronic lymphocytic leukemia, small lymphocytic leukemia, and relapsed/refractory follicular lymphoma. Zanubrutinib has previously been granted Fast Track designation for the treatment of patients with WM.²

“We are very excited to receive the Breakthrough Therapy designation from the FDA,” Jane Huang, MD, chief medical officer of hematology at BeiGene, said in a statement.¹ “Zanubrutinib has been designed to maximize BTK occupancy and minimize off-target effects. We believe that the Breakthrough Therapy designation underscores the potential of zanubrutinib as a meaningful treatment for patients with MCL who have received at least 1 prior therapy.”

References

• BeiGene Receives U.S. FDA Breakthrough Therapy Designation for Zanubrutinib in Mantle Cell Lymphoma [news release]. BeiGene’s website. http://ir.beigene.com/phoenix.zhtml?c=254246&p=irol-newsArticle&ID=2383285. Accessed January 15, 2019.
• BeiGene Announces Clinical Results of Zanubrutinib in Mantle Cell Lymphoma From Two Presentations at the 60th American Society of Hematology Annual Meeting [news release]. BeiGene’s website. http://ir.beigene.com/phoenix.zhtml?c=254246&p=irol-newsArticle&ID=2378923. Accessed January 15, 2019.