BEIJING – Chinese regulators granted the marketing nod to Beijing-based Beigene Ltd.‘s PD-1 antibody, tislelizumab, for treating patients with classical Hodgkin lymphoma (cHL) who have received at least two prior therapies. To be sold under the Chinese trade name Baize’an, tislelizumab is Beigene’s first drug to win approval in China, following an FDA approval for its BTK inhibitor, Brukinsa (zanubrutinib), last month.

“We are preparing the commercialization of tislelizumab, and we will start supplying the drug soon,” Beigene’s media relations officer, Min Xiao, told BioWorld Asia.

The PD-1 antibody will be manufactured by Boehringer Ingelheim GmbH at its facility in Shanghai. As the commercial supplier. Beigene will also provide additional commercial supply through its own biologics manufacturing facility in Guangzhou.

Tislelizumab is a humanized IgG4 anti-PD-1 monoclonal antibody specifically designed to minimize binding to FcγR, which is believed to play an essential role in activating phagocytosis in macrophages to minimize its negative impact on T effector cells.

The National Medical Products Administration (NMPA) approval was based on a pivotal phase II trial that demonstrated an objective response rate of 76.9% and a complete response rate of 61.5%. The recommended dose of tislelizumab is 200 mg administered as an intravenous infusion every three weeks, until disease progression or intolerable toxicity occur.

“Tislelizumab is a differentiated anti-PD-1 antibody and has demonstrated encouraging clinical efficacy and safety in patients with relapsed/refractory cHL. We look forward to its further development in a broad array of solid tumors and hematological malignancies,” said Beigene CEO John Oyler.

The Chinese biotech is now conducting 15 registration-enabling clinical trials to evaluate tislelizumab in 23 countries and global regions in prevalent cancer types such as lung, liver, esophageal and gastric cancers, according to Wendy Yan, Beigene’s senior vice president and global head of regulatory affairs. More than 4,800 patients have been enrolled in development programs for tislelizumab.

Beigene is also seeking another NDA for tislelizumab in patients with previously treated locally advanced or metastatic urothelial carcinoma. The application has been accepted and granted priority review by China’s NMPA.

A late entrant

Tislelizumab is the fourth China-developed, and the sixth overall PD-1 antibody approved in China over the last two years.

China first approved Bristol-Myers Squibb Co.'s Opdivo (nivolumab) for previously treated non-small-cell lung cancer and Merck & Co. Inc.'s Keytruda (pembrolizumab) for unresectable or metastatic melanoma in June and July 2018, respectively.

Then in December 2018 and June 2019, the country gave more green lights to Shanghai Junshi Biosciences Co. Ltd.'s Tuoyi (toripalimab) for metastatic melanoma, Innovent Biologics Inc.'s Tyvyt (sintilimab injection) for recurrent or refractory cHL, and Jiangsu Hengrui Medicine Co. Ltd.’s camrelizumab, also for recurrent or refractory cHL.

Earlier this month, Astrazeneca plc’s Imfinzi (durvalumab) was approved in the country for treating patients with unresectable, stage III non-small-cell lung cancer, becoming the first PD-L1 inhibitor to enter the China market.

“Combination therapies will be the future for PD-1/PD-L1 antibodies,” Kai Sun, an analyst from Shanghai-based Green River Investment, told BioWorld Asia. “PD-1/PD-L1 antibodies are getting less competitive in the Chinese market if only used as monotherapies.”

Biotech executives are well aware of that; China’s biologic scene is homogenized with a lot of PD-1/PD-L1 candidates, and the competition is fierce.

“The key to standing out is to find a combination therapy with PD-1,” said Lianshan Zhang, Hengrui’s senior vice president and global R&D president, during the Chinatrials 12 Summit last month.

Junshi is exploring the possibility of using its PD-1 in combination with paclitaxel for injection (albumin-bound). Innovent, meanwhile, is investigating combination therapies of its PD-1 with a conjugate of angiopep-2 and paclitaxel, and with Chi-Med’s VEGFR, FGFR1 and CSF-1R inhibitor, surufatinib.

Other Chinese biotech companies are also seeking ways to differentiate their PD-1/PD-L1 candidates. For example, 3D Medicines (Beijing) Co. Ltd. and Jiangsu Alphamab Biopharmaceuticals Co. Ltd. are co-developing a subcutaneously injectable PD-L1 inhibitor that could be the first in the world.

Alphamab is turning its focus on PD-L1-based bispecific antibodies with a PD-L1/CTLA4 bispecific antibody in its pipeline. Akeso Biopharma Inc., of Guangzhou, is developing what it says is the world's first PD-1/VEGF bispecific antibody.

And on the financial front, winning a place on China’s national reimbursement drug list is critical for biotechs to stand out from the competition.

When China updated the list last month, Innovent’s Tyvyt was the only PD-1 antibody included. Under the reimbursement scheme, Tyvyt is priced 63.73% lower, but the biotech’s CEO said he is confident that more sales volume, along with other advantages, can offset the price cut.

“This helps us build-up relationships with hospitals and strengthen understanding of Tyvyt ahead of approvals for much larger indications,” CEO Michael Yu told BioWorld Asia in a previous interview.

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