BeiGene Seeks FDA Approval for BTK Inhibitor, Strikes Oncology Deal with BITT

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BeiGene’s Bruton’s kinase inhibitor Brukinsa (zanabrutinib) could be on its way for regulatory approval as a potential treatment for Waldenström’s macroglobulinemia (WM), a type of non-Hodgkin lymphoma.

On Thursday, the company announced the U.S. Food and Drug Administration accepted a supplemental new drug application (sNDA) for Burkinsa in this indication. The FDA set a Prescription Drug User Fee Act (PDUFA) target action date of Oct. 18 of this year. WM is a rare and incurable form of non-Hodgkin lymphoma. There are limited FDA-approved treatment options. WM typically affects older adults and is primarily found in the bone marrow, however lymph nodes and the spleen can also be affected. In the U.S., there are about 5,000 new cases of WM each year.

Jane Huang, BeiGene’s chief medical officer of Hematology, said BTK inhibitors have transformed the treatment of WM in recent years. However, she noted that discrepancies in response exist in patients with different subtypes, and said toxicity can remain an issue for these patients. She expressed hope that Brukinsa will become a new treatment option for patients with WM in the United States.

The SNDA was based on data from the Phase III ASPEN trial, which compared Brukinsa against Johnson & Johnson’s Imbruvica (ibrutinib) as a potential treatment for WM. Imbruvica paired with Rituxin was approved for the treatment of Waldenström’s macroglobulinemia in 2018. When the study data was first released in 2019, BeiGene said Brukinsa did not achieve statistical significance on its primary endpoint of superiority in complete response (CR) and very good partial response (VGPR) rates against the J&J drug.

However, the company said Brukinsa demonstrated a higher VGPR rate as well as improvements in safety and tolerability in this first randomized comparative trial to read out within the BTK inhibitor class. Although Brukinsa did not hit its primary endpoint, data from the Phase III ASPEN trial showed 28.4% of Brukinsa patients achieved VGPR compared to 19.2% in the Imbruvica arm. Also, Brukinsa had a more favorable safety profile, Beigene said at the time.

In addition to data from the ASPEN study, the sNDA includes supportive data from the pivotal Phase II trial of zanubrutinib in relapsed/refractory WM conducted in China and the global Phase I/II trial in patients with B-cell malignancies.

Brukinsa has been approved in the United States as a treatment for mantle cell lymphoma.

In addition to the sNDA, BeiGene also struck a licensing agreement with Boston Immune Technologies and Therapeutics, Inc. (BITT) to develop that company’s tumor necrosis factor (TNF) receptor 2 (TNFR2) antagonist antibodies. The two companies will conduct Phase I clinical trials of BITR2101, BITT’s lead TNFR2 antagonist antibody, including planned combination studies with tislelizumab, BeiGene’s anti-PD-1 antibody.

TNFR2 is a member of the TNF receptor superfamily that is selectively expressed on many tumor types as a surface oncogene and has been shown to proliferate tumor cell growth. TNFR2 is also expressed on suppressive immune cells in the tumor microenvironment, including regulatory T cells (Tregs) and myeloid-derived suppressor cells, and has been identified as a potential driver of immune escape and tumor development as well as resistance to checkpoint blockade.

Luson Luo, BeiGene’s head of external innovation, called TNFR2 an interesting target because of the high expression on the suppressive cells in the tumor microenvironment. Luo said there is also a growing consensus that targeting TNFR2 may be a novel and effective approach to treating cancer.

Under the terms of the agreement, BITT will receive an upfront payment and potential near-term milestone payments totaling $16.6 million. BITT is eligible to receive development, regulatory, and sales milestones up to $105 million. Gene also invested $4 million in BITT’s Series A preferred stock financing.