BEIJING – Beijing-based Chinese biotech giant Beigene Ltd. said Brukinsa (zanubrutinib) won accelerated FDA approval to treat adults with mantle cell lymphoma (MCL) who received at least one prior therapy. This is the first China-discovered innovative cancer drug to win FDA clearance.

Beigene said Brukinsa is the only FDA-approved BTK inhibitor shown to deliver 100% median occupancy in peripheral blood cells. It is also the only BTK inhibitor that can be taken once or twice daily. Brukinsa is expected to be launched in the U.S. in the coming weeks.

The overnight news of the FDA approval shot Beigene's share prices up 10% on Friday morning in Hong Kong (HKEX:06160). On Nasdaq, its shares (BGNE) closed Friday at $198.25.

The biotech also noted that continued approval for MCL may be contingent upon verification and description of clinical benefit in a confirmatory trial.

"This historical breakthrough signifies international recognition for Chinese R&D capabilities," said Xiaobin Wu, general manager of China and president of Beigene. "It demonstrates that Chinese innovative-driven biotech companies can benefit patients not just in China but also the world."

Brukinsa is a small-molecule BTK inhibitor that was designed to maximize target occupancy and minimize off-target binding. It is part of the same class as the better-known Imbruvica (ibrutinib, Abbvie Inc./Johnson & Johnson and Calquence (acalabrutinib, Astrazeneca plc), though Brukinsa stands out from the other two with its high plasma concentrations for a sustained duration of time.

The FDA granted the drug fast track designation in July 2018 and approval is based on an overall response rate (ORR) of 84% from two single-arm clinical trials, in which independent review committee-assessed ORR per 2014 Lugano Classification was the primary endpoint.

In the multicenter phase II trial, the ORR was 84%, including 59% complete response and 24% partial response. The median duration of response (DOR) was 19.5 months (95% CI: 16.6, NE) and median follow-up time on study was 18.4 months.

And in the global phase I/II trial, the ORR was again 84% (95% CI: 67%, 95%), including 22% complete response and 62% partial response. The median DOR was 18.5 months (95% CI:12.6, NE) and median follow-up time on study was 18.8 months.

Patients treated with Brukinsa experienced adverse reactions such as pneumonia (11%) and hemorrhage (5%). Other common reactions include decreased neutrophil count, decreased platelet count, upper respiratory tract infection, decreased white blood cell count, decreased hemoglobin, rash, bruising, diarrhea, cough, musculoskeletal pain, urinary tract infection, blood in the urine, fatigue and constipation.

"BTK inhibition is an established mode of treatment for patients with MCL, but many patients treated with previously approved BTK inhibitors do not fully respond to BTK therapy or are forced to discontinue treatment early due to side effects," said Luhua Wang, a professor of the Department of Lymphoma and Myeloma, Division of Cancer Medicine at the University of Texas MD Anderson Cancer Center. "Today, we have a new option for our adult patients who have received one prior systemic or targeted therapy and are living with MCL."

Currently, Beigene is conducting 16 clinical trials on zanubrutinib. Besides developing it as a monotherapy, Beigene is also exploring the potential of the drug in combination therapies with CD20 inhibitor Gazyva (obinutuzumab, Roche Holding AG) and its PD-1 antibody, tislelizumab.

For the China market, Beigene is seeking NDA approval for relapsed/refractory MCL and relapsed/refractory chronic lymphocytic leukemia or small lymphocytic lymphoma. The drug was granted priority review by the NMPA.

Zanubrutinib is one of Beigene's core products. Another one is its PD-1 antibody tislelizumab, which is set to enter the China market for the treatment of relapsed/refractory classical Hodgkin lymphoma by the end of this year. It will be the sixth PD-1 antibody, or the fourth homegrown PD-1 antibody, approved in China.

Earlier this month, Beigene received wide industry attention when it announced a mega-deal with Amgen Inc., a multinational U.S. biopharmaceutical headquartered in Thousand Oaks, Calif., to co-develop 20 oncology products globally. Amgen is also buying a 20.5% stake in the Chinese biotech for $2.7 billion in cash. (See BioWorld, Nov. 4, 2019.)

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