BeiGene's PD-1 Inhibitor Baizean (Tislelizumab) Receives NMPA Approval, Set to Compete Directly with Tyvyt and AiRuiKa

On December 28, 2019, VCBeat learned that BeOne Medicines announced today that its anti-PD-1 antibody drug, Baizean (generic name: tislelizumab injection), had been approved by the National Medical Products Administration (NMPA) on December 27 for the treatment of relapsed or refractoryClassical Hodgkin Lymphoma (R/R cHL) patient, and the new drug application had previously been included in the priority review program by the NMPA. Baizean is the first independently developed anti-cancer new drug approved in China by BeOne Medicines, following the U.S. Food and Drug Administration (FDA) approval of its self-developed BTK inhibitor BRUKINSA™ (zanubrutinib).

Among the PD-1 monoclonal antibodies previously approved for marketing, Innovent Biologics’ Tyvyt (sintilimab) and Jiangsu Hengrui Medicine’s AiRuiKa (camrelizumab) have indications identical to those newly approved for Baizean. This means that these three PD-1 monoclonal antibodies will engage in direct competition in the Chinese market.

BeOne Medicines (NASDAQ: BGNE; HKEX: 06160) is a commercial-stage biopharmaceutical company focused on the development and commercialization of innovative molecularly targeted and tumor immunology drugs for cancer treatment. Baizean (tislelizumab) is BeOne Medicines’ second approved self-developed drug and the first self-developed novel anti-cancer drug approved for marketing in China.

Baizean is a humanized IgG4 anti-PD-1 monoclonal antibody designed to avoid binding to FcγR receptors on the surface of macrophages, thereby preventing the activation of macrophage phagocytosis and reducing its negative impact on T effector cells.

Previously, another new indication application for Baizean in patients with previously treated locally advanced or metastatic urothelial carcinoma (UC) has been accepted by the Center for Drug Evaluation (CDE) of the National Medical Products Administration and included in the priority review.

As a biologic that has entered the commercialization phase under the pilot program for the Marketing Authorization Holder (MAH) system, BAIZEAN will be manufactured by Boehringer Ingelheim Biopharma (China) Co., Ltd. after approval to ensure commercial supply. Founded in 1885, Boehringer Ingelheim has over 35 years of experience in biopharmaceutical manufacturing. To date, its contract manufacturing organization (CMO) services, provided by more than 3,600 employees worldwide, have helped bring over 30 drugs to markets around the globe. BeOne Medicines and Boehringer Ingelheim Biopharma are currently actively preparing for the commercial supply of BAIZEAN following its market launch in China.

The approval of Baizean by the National Medical Products Administration (NMPA) of China is based on clinical study results, including those from the pivotal, single-arm, multicenter Phase 2 clinical trial BGB-A317-203 (ClinicalTrials.gov Identifier: NCT03209973) conducted in China. Patients included in the efficacy analysis set had a minimum follow-up duration of 12 months, with a median follow-up time of 14 months. The objective response rate (ORR), assessed by an Independent Review Committee (IRC), was 76.9%, including a complete response (CR) rate of 61.5%.

In the BGB-A317-203 trial involving patients with relapsed or refractory classical Hodgkin lymphoma (R/R cHL), the most common adverse reactions (≥ 10%) were pyrexia, hypothyroidism, weight increased, pruritus, decreased white blood cell count, upper respiratory tract infection, increased alanine aminotransferase (ALT), rash, decreased neutrophil count, cough, fatigue, and increased blood bilirubin. Grade ≥ 3 adverse reactions with an incidence of ≥ 2% included pneumonitis, weight increased, severe skin reactions, and hypertension. No drug-related deaths were observed.

Baize’an is similar to other products in its class and may cause immune-related adverse events, primarily including pneumonitis, diarrhea and colitis, hepatitis, endocrine disorders (hypothyroidism, hyperthyroidism and other thyroid diseases, adrenal insufficiency, hyperglycemia, and type 1 diabetes mellitus), and cutaneous adverse reactions. Additionally, nephritis, pancreatitis, myocarditis, and other immune-related events have been reported occasionally.

Baizean is administered via intravenous infusion at a recommended dose of 200 mg every three weeks. Treatment should continue until disease progression or the occurrence of intolerable toxicity.

Dr. Wu Xiaobin, General Manager of BeOne Medicines’ China region and President of the company, stated: “We have always been committed to improving treatment standards for cancer patients worldwide. As a groundbreaking discovery in the field of oncology, tumor immunotherapy is bringing new treatment options and hope for cure to cancer patients globally. As a distinctive anti-PD-1 antibody drug, Baizean has already demonstrated encouraging clinical efficacy and safety in treating patients with relapsed or refractory classical Hodgkin lymphoma. We are highly optimistic about its future development across a range of solid tumor and hematologic malignancy indications.”

Professor Zhu Jun, Director of the Department of Medical Oncology and Director of the Lymphoma Department at Peking University Cancer Hospital, stated, “PD-1 antibody drugs have brought new options for the treatment of lymphoma. Tislelizumab (Baizean), a PD-1 antibody drug independently developed by BeOne Medicines, has demonstrated significant clinical efficacy, with a complete response rate exceeding 60% as monotherapy for relapsed or refractory classical Hodgkin lymphoma, along with a favorable safety profile. The approval of Tislelizumab for marketing in China provides a meaningful treatment option for domestic patients with relapsed or refractory classical Hodgkin lymphoma.”

Ms. Yan Xiaojun, Senior Vice President and Head of Global Regulatory Affairs at BeOne Medicines, commented, “Currently, BeOne Medicines is conducting 15 registrational clinical trials of Baizean in 23 countries and regions worldwide, covering multiple high-incidence cancers including lung cancer, liver cancer, esophageal cancer, and gastric cancer, with a total enrollment of more than 4,800 patients. We sincerely thank these clinical experts and patients for their participation, which has enabled Baizean to advance from the laboratory to clinical development and ultimately gain approval for marketing, thereby benefiting more cancer patients.”

Hodgkin lymphoma is a type of malignant tumor involving the lymph nodes and lymphatic system. Classical Hodgkin lymphoma is the most common subtype, accounting for approximately 95% of all Hodgkin lymphoma cases. It has the highest incidence among young adults aged 15–30 years and adults over 55 years of age. Lymphadenopathy is often the initial presenting symptom, with potential involvement of the liver, spleen, bone marrow, and other organs in advanced stages. First-line chemoradiotherapy has significantly improved survival outcomes for patients with classical Hodgkin lymphoma. However, approximately 5–10% of patients have primary refractory disease, and 10–30% experience relapse after achieving initial remission. These patients have a poor prognosis, and traditional salvage regimens offer limited efficacy, indicating an unmet clinical need for more effective treatment options.

Baizean (tislelizumab) is a humanized IgG4 monoclonal antibody against programmed death receptor 1 (PD-1), designed to minimize binding to FcγR receptors in macrophages. Preclinical data indicate that binding to FcγR receptors in macrophages activates antibody-dependent cell-mediated cytotoxicity of T cells, thereby reducing the antitumor activity of PD-1 antibodies. Tislelizumab is the first candidate drug developed by BeOne Medicines’ immuno-oncology biologics platform and is currently undergoing clinical trials as monotherapy and in combination therapies, with development targeting a broad range of indications for solid tumors and hematologic malignancies.

Baizean has been approved by the National Medical Products Administration (NMPA) of China for the treatment of patients with relapsed or refractory classical Hodgkin lymphoma who have received at least two prior lines of systemic chemotherapy. Another new drug application submitted by Baizean for the treatment of patients with previously treated locally advanced or metastatic urothelial carcinoma has been included in the priority review program by the Center for Drug Evaluation (CDE) under the NMPA and is currently under review.

Following its market launch, Baizean will be manufactured by Boehringer Ingelheim Biopharmaceuticals. In addition, the first phase of BeOne Medicines’ Guangzhou Biologics Manufacturing Base, which covers an area of 100,000 square meters, represents a total investment exceeding RMB 2.3 billion, and is dedicated to the process development and commercial-scale manufacturing of large-molecule biologics, was completed in September this year. Upon passing relevant qualification validations and obtaining necessary approvals, the facility will provide additional commercial supply for the subsequent large-scale use of Baizean, ensuring adequate production capacity.

Baizean is being developed as a monotherapy and in combination regimens for a series of indications in the treatment of solid tumors and hematologic malignancies. Currently, 15 registrational clinical trials are underway in China and globally, including 11 Phase 3 trials and four pivotal Phase 2 trials.

Baizean has not yet been approved in countries and regions outside China.

BeOne Medicines is a global, commercial-stage, R&D-driven biotechnology company focused on the development of molecularly targeted and immuno-oncology therapies. With more than 3,000 employees across China, the United States, Australia, and Switzerland, BeOne Medicines maintains a pipeline that includes novel oral small-molecule and monoclonal antibody anticancer agents. The company is also building combination regimens for cancer treatment, aiming to make a sustained and profound impact on the lives of patients with cancer. In the United States, BeOne Medicines markets its internally developed BTK inhibitor BRUKINSA® (zanubrutinib). In China, its anti-PD-1 antibody therapy Baizean® (tislelizumab) has received marketing approval. Under license from Celgene Corporation LLC (a Bristol Myers Squibb company), BeOne Medicines markets ABRAXANE® (paclitaxel for injectable suspension [nanoparticle albumin-bound]), Revlimid® (lenalidomide), and VIDAZA® (azacitidine for injection) in China.