BeiGene Receives FDA Approval For TEVIMBRA ® For The Treatment Of Advanced Or Metastatic Esophageal Squamous Cell Carcinoma Following Prior Chemotherapy

BASEL, Switzerland & BEIJING & CAMBRIDGE, Mass.--( BUSINESS WIRE )--BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160; SSE: 688235), a global oncology company, today announced that the Food and Drug Administration of The United States (FDA) approved TEVIMBRA ^® (tislelizumab-jsgr) as monotherapy for the treatment of adult patients with unresectable or metastatic esophageal squamous cell carcinoma (ESCC) after prior systemic chemotherapy that did not include a PD-(L) inhibitor. )1. TEVIMBRA will be available in the US in the second half of 2024.

"The FDA's approval of TEVIMBRA for ESCC patients who have previously received chemotherapy, along with the ongoing review of our BLA for first-line ESCC patients, represents a significant step in our commitment to bring this therapy to more patients worldwide," said Mark Lanasa, M.D., Ph.D., medical director of solid tumors at BeiGene. "As BeiGene's first drug candidate produced through our immuno-oncology program and second drug approved in the United States, TEVIMBRA is poised to be a critical pillar of our solid tumor development program, spanning more than 17 clinical trials. that allow registration in more than 30 countries in all regions of the world.

The approval is based on the RATIONALE 302 trial, which met its primary endpoint in the intention-to-treat (ITT) population with a statistically significant and clinically meaningful survival benefit for TEVIMBRA compared to chemotherapy. In the ITT population, median overall survival (OS) in the TEVIMBRA arm was 8.6 months (95% CI: 7.5, 10.4) vs. 6.3 months (95% CI: 5.3, 7.0) in the chemotherapy group (p=0.0001; hazard ratio [HR]=0.70 [95% CI: 0.57, 0.85]). The safety profile of TEVIMBRA was favorable compared to chemotherapy. ⁱ The most common adverse reactions (≥20%) of TEVIMBRA, including laboratory abnormalities, were increased glucose, decreased hemoglobin, decreased lymphocytes, decreased sodium, decreased albumin, increased alkaline phosphatase , anemia, fatigue, increased AST, musculoskeletal pain, decreased weight, increased ALT, and cough. ^Yo

"Patients diagnosed with advanced or metastatic ESCC, the most common histologic subtype of esophageal cancer, often progress after initial treatment and require new options," Syma Iqbal, MD, associate professor of clinical medicine, Section Chief of Gastrointestinal Oncology , Division of Medical Oncology and Chief Medical Oncologist, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California. "The RATIONALE 302 trial demonstrated that patients with previously treated ESCC who received TEVIMBRA achieved a clinically significant survival benefit, highlighting its potential as an important treatment option for these patients."

Tislelizumab received approval from the European Commission for advanced or metastatic ESCC after prior chemotherapy in 2023 and a positive opinion from the Committee for Medicinal Products for Human Use of the European Medicines Agency (EMA) in February 2024 as a treatment for lung cancer. non-small cell in three indications.

The FDA is also reviewing biologics license applications (BLAs) for tislelizumab as a first-line treatment for patients with unresectable, recurrent, locally advanced, or metastatic ESCC and patients with unresectable or locally advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma. metastatic. The planned start dates for the action are July and December 2024, respectively.

BeiGene has launched more than 17 potentially registrable trials with TEVIMBRA, of which 11 randomized phase 3 trials and four phase 2 trials have already yielded positive results. Through these trials, TEVIMBRA has demonstrated its potential to provide clinically significant improvements in survival and quality of life benefits for hundreds of thousands of cancer patients across a range of tumor types, in many cases regardless of cancer status. PD-(L)1, both as monotherapy and in combination with other regimens. To date, TEVIMBRA has been prescribed to more than 900,000 patients worldwide.

About RATIONALE 302

RATIONALE 302 is a global, randomized, open-label, Phase 3 study ( NCT03430843 ) designed to investigate the efficacy and safety of TEVIMBRA compared to investigator's choice chemotherapy as second-line treatment for patients with unresectable, locally advanced or metastatic. The study randomized 512 patients from 132 research centers in 11 countries in Europe, Asia and North America.

About ESCC

Worldwide, esophageal cancer (EC) is the sixth most common cause of cancer-related deaths, and ESCC is the most common histological subtype, accounting for nearly 90% of ECs. ⁱⁱ An estimated 957,000 new cases of EC will occur in 2040, an increase of almost 60% over 2020 and underscoring the need for additional effective treatments.i ⁱ EC is a rapidly fatal disease, and more Two-thirds of patients have advanced or metastatic disease at diagnosis, with an expected five-year survival rate of less than 6% for those with distant metastases. ⁱⁱⁱ

About TEVIMBRA ^® (tislelizumab-jsgr)

Tislelizumab is a uniquely designed humanized immunoglobulin G4 (IgG4) monoclonal antibody against programmed cell death protein 1 (PD-1) with high binding affinity and specificity against PD-1. It is designed to minimize binding to Fc-gamma (Fcγ) receptors on macrophages, helping the body's immune cells detect and fight tumors.

US indications and important safety information for TEVIMBRA (tislelizumab-jsgr)

INDICATION

TEVIMBRA (tislelizumab-jsgr), as a single agent, is indicated for the treatment of adult patients with unresectable or metastatic esophageal squamous cell carcinoma following prior systemic chemotherapy that did not include a PD-(L)1 inhibitor.

WARNINGS AND PRECAUTIONS

Serious and fatal immune-mediated adverse reactions

TEVIMBRA is a monoclonal antibody that belongs to a class of drugs that bind to the programmed death-1 (PD-1) receptor or PD-ligand 1 (PD-L1), blocking the PD-1/PD-L1 pathway, thus eliminating the inhibition of the immune response, potentially breaking peripheral tolerance and inducing immune-mediated adverse reactions.

Immune-mediated adverse reactions, which can be severe or fatal, can occur in any organ system or tissue. Immune-mediated adverse reactions may occur at any time after initiating treatment with a PD-1/PD-L1 blocking antibody. Although immune-mediated adverse reactions usually occur during treatment with PD-1/PD-L1 blocking antibodies, immune-mediated adverse reactions may also occur after discontinuation of treatment with PD-1/PD-L1 blocking antibodies. The important immune-mediated adverse reactions listed here may not include all possible serious and fatal immune-mediated reactions.

Early identification and treatment of immune-mediated adverse reactions are essential to ensure the safe use of PD-1/PD-L1 blocking antibodies. Monitor patients closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions. Assess liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment. In cases of suspected immune-mediated adverse reactions, initiate appropriate studies to exclude alternative etiologies, including infection. Promptly institute medical treatment, including consultation with specialists if appropriate.

Interrupt or permanently suspend TEVIMBRA depending on severity. In general, if TEVIMBRA requires interruption or discontinuation, administer systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue taper for at least 1 month. Consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reactions are not controlled with corticosteroids.

Immune-mediated pneumonitis

TEVIMBRA can cause immune-mediated pneumonitis, which can be fatal. In patients treated with other PD-1/PD-L1 blocking antibodies, the incidence of pneumonitis is higher in patients who have received prior thoracic radiation.

Immune-mediated pneumonitis occurred in 3.8% (75/1972) of patients receiving TEVIMBRA, including fatal (0.2%), grade 4 (0.3%), grade 3 (1.4%) adverse reactions. %) and grade 2 (1.7%). Pneumonitis led to permanent discontinuation of TEVIMBRA in 35 (1.8%) patients and discontinuation of TEVIMBRA in 27 (1.4%) patients.

All patients with pneumonitis required systemic corticosteroids. Immune-mediated pneumonitis resolved in 47% of the 75 patients. Of the 27 patients in whom TEVIMBRA was discontinued due to pneumonitis, 18 restarted TEVIMBRA after symptom improvement; Of these, 3 (17%) patients had recurrence of pneumonitis.

Immune-mediated colitis

TEVIMBRA can cause immune-mediated colitis, which can be fatal. Cytomegalovirus (CMV) infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis treated with PD-1/PD-L1 blocking antibodies. In cases of corticosteroid-refractory colitis, consider repeating the infectious workup to exclude alternative etiologies.

Immune-mediated colitis occurred in 0.9% (17/1972) of patients receiving TEVIMBRA, including grade 3 (0.4%) and grade 2 (0.5%) adverse reactions. Colitis led to permanent discontinuation of TEVIMBRA in 2 (0.1%) patients and discontinuation of TEVIMBRA in 10 (0.5%) patients. All 17 patients received systemic corticosteroids. Twelve (71%) of the 17 patients received high doses of systemic corticosteroids. Two (12%) of the 17 patients received immunosuppressive treatment. Immune-mediated colitis resolved in 88% of the 17 patients. Of the 10 patients in whom TEVIMBRA was discontinued due to colitis, 8 restarted TEVIMBRA after symptom improvement; Of these, 1 (13%) patient had colitis recurrence.

Immune-mediated hepatitis

TEVIMBRA can cause immune-mediated hepatitis, which can be fatal.

Immune-mediated hepatitis occurred in 1.7% (34/1972) of patients receiving TEVIMBRA, including fatal (0.1%), grade 4 (0.1%), grade 3 (1%) adverse reactions. and grade 2 (0.6%). Immune-mediated hepatitis led to definitive discontinuation in 9 (0.5%) patients and discontinuation of TEVIMBRA in 20 (1%) patients. All patients received systemic corticosteroids. Twenty-nine (85%) of the 34 patients received high-dose systemic corticosteroids. One patient (2.9%) of the 34 received immunosuppressive treatment. Immune-mediated hepatitis resolved in 59% of the 34 patients. Of the 20 patients in whom TEVIMBRA was discontinued due to hepatitis, 12 restarted TEVIMBRA after symptom improvement; of these, 2 (17%) patients had hepatitis recurrence.

Immune-mediated endocrinopathies

Suprarrenal insufficiency

TEVIMBRA may cause immune-mediated adrenal insufficiency. In case of grade 2 or higher adrenal insufficiency, initiate symptomatic treatment, including hormone replacement according to clinical indication. Discontinue TEVIMBRA depending on severity.

Immune-mediated adrenal insufficiency occurred in 0.3% (6/1972) of patients receiving TEVIMBRA, including Grade 4 (0.1%), Grade 3 (0.1%), and Grade 2 (0.1%) adverse reactions. 2 %). Adrenal insufficiency did not lead to permanent discontinuation of TEVIMBRA. TEVIMBRA was discontinued in 5 of the 6 patients. All 6 patients received systemic corticosteroids. Two (33%) of the 6 patients received high doses of systemic corticosteroids. Adrenal insufficiency resolved in 17% of the 6 patients.

Hypophysitis

TEVIMBRA may cause immune-mediated hypophysitis. Hypophysitis may present with acute symptoms associated with mass effect such as headache, photophobia or visual field defects. Hypophysitis can cause hypopituitarism. Initiate hormone replacement as clinically indicated. Discontinue or permanently discontinue TEVIMBRA depending on severity.

Hypophysitis/hypopituitarism occurred in 0.1% (1/1972) of patients receiving TEVIMBRA, including one Grade 2 adverse reaction (0.1%). There was no need to interrupt or discontinue treatment with TEVIMBRA.

Thyroid disorders

TEVIMBRA may cause immune-mediated thyroid disorders. Thyroiditis can occur with or without endocrinopathy. Hyperthyroidism can be followed by hypothyroidism. Initiate hormone replacement for hypothyroidism or institute medical management of hyperthyroidism as clinically indicated. Suspend or permanently discontinue TEVIMBRA depending on severity. .

Thyroiditis: Immune-mediated thyroiditis occurred in 0.4% (7/1972) of patients receiving TEVIMBRA, including Grade 2 adverse reactions (0.3%). Thyroiditis did not lead to permanent discontinuation of TEVIMBRA. TEVIMBRA was discontinued in 1 (0.1%) patient. One (14%) of the 7 patients received systemic corticosteroids. Thyroiditis resolved in 29% of the 7 patients.

Hyperthyroidism: Immune-mediated hyperthyroidism occurred in 0.6% (12/1972) of patients receiving TEVIMBRA, including Grade 3 (0.1%), and Grade 2 (0.5%) adverse reactions. Hyperthyroidism led to permanent discontinuation of TEVIMBRA in 1 (0.1%) patient and discontinuation of TEVIMBRA in 1 (0.1%) patient. One (8%) of the 12 patients received systemic corticosteroids. Hyperthyroidism resolved in 92% of the 12 patients.

Hypothyroidism: Immune-mediated hypothyroidism occurred in 7% (132/1972) of patients receiving TEVIMBRA, including Grade 4 (0.1%) and Grade 2 (5%) adverse reactions. TEVIMBRA was not permanently discontinued in any patient, while treatment was discontinued in 6 (0.3%) patients. Two (1.5%) of the 132 patients received systemic corticosteroids. All 132 patients received hormone replacement therapy. Hypothyroidism resolved in 27% of the 132 patients. The majority (86%) of patients with hypothyroidism required long-term thyroid hormone replacement.

Type 1 diabetes mellitus, which can cause diabetic ketoacidosis

Cases of type 1 diabetes mellitus with PD-1/PD-L1 blocking antibodies have been reported. Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Start insulin treatment according to clinical indication. Suspend or permanently discontinue TEVIMBRA depending on severity.

Immune-mediated nephritis with renal dysfunction

TEVIMBRA can cause immune-mediated nephritis, which can be fatal.

Immune-mediated nephritis with renal dysfunction occurred in 0.4% (7/1972) of patients receiving TEVIMBRA, including Grade 4 (0.1%), Grade 3 (0.1%), and Grade 2 adverse reactions ( 0.2%). TEVIMBRA was permanently discontinued in 3 (0.2%) patients and treatment was discontinued in 3 (0.2%) patients. All patients received systemic corticosteroids. Nephritis with renal dysfunction resolved in 57% of the 7 patients. Of the 3 patients in whom TEVIMBRA was discontinued due to nephritis, 2 restarted TEVIMBRA after symptom improvement and one patient had a recurrence of nephritis.

Immune-mediated dermatological adverse reactions

TEVIMBRA may cause immune-mediated skin rashes or dermatitis. Cases of severe cutaneous adverse reactions (SACR), including exfoliative dermatitis, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN), some with fatal outcomes, have been reported. Topical emollients and/or topical corticosteroids may be appropriate to treat mild to moderate non-exfoliative rashes. Suspend or permanently discontinue TEVIMBRA depending on severity.

Immune-mediated dermatologic adverse reactions occurred in 1.2% (24/1972) of patients receiving TEVIMBRA, including grade 4 (0.2%), grade 3 (0.4%), and grade 2 (0.4%) adverse reactions. ,4 %). Dermatologic adverse reactions led to permanent discontinuation of TEVIMBRA in 3 (0.2%) patients and discontinuation of TEVIMBRA in 9 (0.5%) patients. Twenty-three (96%) of the 24 patients received systemic corticosteroids. Immune-mediated skin reactions resolved in 58% of the 24 patients. Of the 9 patients in whom TEVIMBRA was discontinued due to dermatological adverse reactions, 8 restarted TEVIMBRA after symptom improvement; of these, 2 (25%) patients had recurrence of immune-mediated skin rash.

Other immune-mediated adverse reactions

The following clinically significant immune-mediated adverse reactions occurred at an incidence of less than 1% each in 1972 patients receiving TEVIMBRA: myositis, myocarditis, arthritis, polymyalgia rheumatica, and pericarditis.

The following additional clinically significant immune-mediated adverse reactions have been reported with other PD-1/PD-L1 blocking antibodies, including severe or fatal cases.

Cardiac/Vascular: vasculitis

Nervous system: meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome / myasthenia gravis (including exacerbation), Guillain-Barré syndrome, nerve paresis, autoimmune neuropathy.

Ocular: Uveitis, iritis, and other ocular inflammatory toxicities may occur. Some cases may be associated with retinal detachment. Varying degrees of visual impairment can occur, including blindness. If uveitis occurs in combination with other immune-mediated adverse reactions, consider Vogt-Koyanagi-Harada-like syndrome, as it may require treatment with systemic steroids to reduce the risk of permanent vision loss.

Gastrointestinal: pancreatitis, including increased serum levels of amylase and lipase, gastritis, duodenitis

Musculoskeletal and connective tissue: polymyositis, rhabdomyolysis and associated sequelae, including renal failure

Endocrine: hypoparathyroidism

Other (hematological/immunological): hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenic purpura, solid organ transplant rejection, rejection of other transplants (including corneal graft).

Infusion-related reactions

TEVIMBRA may cause serious or life-threatening infusion-related reactions. Infusion-related reactions occurred in 4.2% (83/1972) of patients receiving TEVIMBRA, including Grade 3 or higher reactions (0.3%). Monitor patients for signs and symptoms of infusion-related reactions.

Decrease the infusion rate for mild (Grade 1) reactions and discontinue the infusion for moderate (Grade 2) infusion-related reactions. In case of serious (Grade 3) or life-threatening (Grade 4) infusion-related reactions, discontinue the infusion and permanently discontinue TEVIMBRA.

Complications of allogeneic HSCT

Fatal and other serious complications may occur in patients who receive an allogeneic hematopoietic stem cell transplant (HSCT) before or after being treated with a PD-1/PD-L1 blocking antibody. Transplant-related complications include hyperacute graft-versus-host disease (GVHD), acute GVHD, chronic GVHD, hepatic veno-occlusive disease after reduced-intensity conditioning, and febrile syndrome requiring steroids (with no identified infectious cause). These complications may occur despite intermediate treatment between PD-1/PD-L1 blockade and allogeneic HSCT.

Monitor patients closely for transplant-related complications and intervene promptly. Consider the benefit versus risks of treatment with a PD-1/PD-L1 blocking antibody before or after allogeneic HSCT.

Embryo-fetal toxicity

Based on its mechanism of action, TEVIMBRA may cause fetal harm when administered to a pregnant woman. Animal studies have shown that inhibition of the PD-1/PD-L1 pathway may lead to an increased risk of immune-mediated rejection of the developing fetus, resulting in fetal death. Warn women of the potential risk to the fetus. Advise women of reproductive potential to use effective contraception during treatment with TEVIMBRA and for 4 months following the last dose.

ADVERSE REACTIONS

Permanent discontinuation of TEVIMBRA due to an adverse reaction occurred in 19% of patients. Adverse reactions leading to permanent discontinuation in ≥1% of patients were bleeding, pneumonitis (including pneumonitis and immune-mediated pneumonitis), and pneumonia.

TEVIMBRA dose interruptions due to an adverse reaction occurred in 23% of patients. Adverse reactions requiring dose interruptions in ≥2% of patients were pneumonia, pneumonitis, and fatigue.

The most common adverse reactions (≥20%), including laboratory abnormalities, were increased glucose, decreased hemoglobin, decreased lymphocytes, decreased sodium, decreased albumin, increased alkaline phosphatase, anemia, fatigue, increased AST, musculoskeletal pain, weight loss, increased ALT, and cough.

See full US prescribing information, including Medication Guide.

About BeiGene

BeiGene is a global oncology company that discovers and develops innovative treatments that are more affordable and accessible to cancer patients around the world. With a broad product portfolio, we are accelerating the development of our diverse portfolio of novel therapeutic products through our internal capabilities and collaborations. We are committed to radically improving access to medicines for many more patients who need them. Our growing global team of more than 10,000 colleagues spans five continents, with administrative offices in Basel, Beijing and Cambridge (USA). To learn more about BeiGene, visit www.beigene.com and follow us on and follow us on LinkedIn and X (formerly known as Twitter).

Forward-looking statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 and other federal securities laws, including statements regarding BeiGene's ability to bring TEVIMBRA to more patients. Worldwide; the future importance of TEVIMBRA in BeiGene's solid tumor development program; the potential for TEVIMBRA to be an important treatment for CCEE; and BeiGene's plans, commitments, aspirations and objectives under the heading "About BeiGene". Actual results may differ materially from those indicated in the forward-looking statements as a result of various important factors, including BeiGene's ability to demonstrate the effectiveness and safety of its drug candidates; the clinical results of its drug candidates, which may not support further development or marketing approval; actions of regulatory agencies, which may affect the initiation, timing and progress of clinical trials and marketing approval; BeiGene's ability to achieve commercial success of its marketed drugs and drug candidates, if approved; BeiGene's ability to obtain and maintain intellectual property protection for its drugs and technology; BeiGene's dependence on third parties to carry out drug development, manufacturing, marketing and other services; BeiGene's limited experience in obtaining regulatory approvals and commercializing pharmaceutical products and its ability to obtain additional financing for operations and to complete the development of its drug candidates and achieve and maintain profitability; and the risks set forth in more detail in the section titled "Risk Factors" of BeiGene's most recent quarterly report on Form 10-Q, as well as discussions of potential risks, uncertainties and other important factors in subsequent filings by BeiGene before the United States Securities and Exchange Commission. All information contained in this press release speaks as of the date hereof, and BeiGene undertakes no obligation to update such information unless required by law.

To access BeiGene's media resources, visit our news and media site .

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ⁱ Shen, L., Kato, K., Kim, SB, Ajani, JA, Zhao, K., He, Z., ... & Van Cutsem, E. (2022). Tislelizumab versus chemotherapy as second-line treatment for advanced or metastatic esophageal squamous cell carcinoma (RATIONALE-302): A randomized phase III study. Journal of Clinical Oncology . 40(26), 3065-3076. DOI: 10.1200/JCO.21.01926
ⁱⁱ Morgan E, et al. The Global Landscape of Esophageal Squamous Cell Carcinoma and Esophageal Adenocarcinoma Incidence and Mortality in 2020 and Projections to 2040: New Estimates From GLOBOCAN 2020. Gastroenterology. 2022 Sep;163(3):649-658.e2. doi: 10.1053/j.gastro.2022.05.054. Epub 2022 Jun 4. PMID: 35671803.
ⁱⁱⁱ National Cancer Institute. Cancer stat facts: esophageal cancer. https://seer.cancer.gov/statfacts/html/esoph.html .

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