On January 28, 2022 Nanjing Bioheng Biotech Co., Ltd. ( hereinafter referred to as Bioheng) reported that its anti-claudin 18.2 autologous CAR-T cell therapy product CTB001 received Orphan Drug Designation (ODD) from the Food and Drug Administration (FDA) for the treatment of gastric cancer (Press release, Bioheng Biotech, JAN 28, 2022, View Source;t-product-received-orphan-drug-designation-odd-from-the-us-fda-301470432.html [SID1234607490]). Gastric cancer has a high incidence in Asian countries such as China and Japan, and the mortality rate ranks the third in the global mortality rate of malignant tumors, behind lung cancer and colorectal cancer. At present, conventional chemotherapy and surgical resection are mainly applied for the gastric cancer treatment, therefore the treatment drugs and methods are very limited.

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About CTB001:

Claudin18.2 is a pan-cancer target and is abnormally expressed in various primary tumors and metastases, including gastric cancer, pancreatic cancer, cholangiocarcinoma, ovarian cancer and lung adenocarcinoma. CTB001 is a fourth-generation autologous CAR-T cell therapy product targeting claudin18.2, which uses Bioheng Explored CAR-T platform technology to enhance the anti-tumor efficacy of the product.

The breakthrough of CAR-T therapy provides a new solution for cancer treatment, with high unmet clinical needs. CTB001 shows excellent efficacy and safety in exploratory clinical studies, and provides strong data support for the upcoming domestic declaration.

Bioheng indicates:

CTB001 is the first clinical validation of Bioheng Explored CAR-T platform technology. It is a very promising immunotherapy that can accurately, quickly and efficiently bring good benefits to claudin18.2-positive cancer patients.

The qualification of CTB001 obtained by FDA for orphan drugs will further accelerate the development and commercialization of cell and gene therapy, and promote Bioheng to enter the global innovative drug market. In the future, we look forward to bringing more products to clinical trials and providing more choices for solving the unmet medical needs.

About ODD:

The Orphan Drug Designation program provides orphan status to drugs and biologics which are defined as those intended for the treatment, prevention or diagnosis of a rare disease or condition, which is one that affects less than 200,000 persons in the US or meets cost recovery provisions of the act. After obtaining the ODD, pharmaceutical companies could receive various incentives for the drug development, including 25% federal tax credit for expenses incurred in conducting clinical research within the United States, Waiver of Prescription Drug User Fee Act (PDUFA) fees for orphan drugs, qualified to compete for research grants from the Office of Orphan Products Development (OOPD) to support clinical studies for orphan drugs, eligibility to receive regulatory assistance and guidance from the FDA in the design of an overall drug development plan and 7-year marketing exclusivity.

On January 28, 2022 Curaleaf Holdings, Inc. (CSE: CURA /OTCQX: CURLF) ("Curaleaf" or the "Company"), a leading international provider of consumer products in cannabis, reported that it will report its financial and operating results for the fourth quarter and fiscal year ended December 31, 2021 after market close on March 3, 2022 (Press release, Curaleaf Holdings, JAN 28, 2022, View Source [SID1234607489]).

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Management will host a conference call and audio webcast that evening at 5:00 p.m. ET consisting of prepared remarks followed by a question and answer session related to the Company’s operational and financial highlights.

For interested individuals unable to join the conference call, a dial-in replay of the call will be available until March 10, 2022 and can be accessed by dialing +1-877-344-7529 (U.S.), +1-855-669-9658 (Canada) or +1-412-317-0088 (International) and entering replay pin number: 4919700.

On January 28, 2022 Pfizer Inc. (NYSE: PFE) reported that the European Commission (EC) granted marketing authorization for LORVIQUA (lorlatinib, available in the U.S. under the brand name LORBRENA) as monotherapy for the treatment of adult patients with anaplastic lymphoma kinase (ALK)- positive advanced non-small cell lung cancer (NSCLC) previously not treated with an ALK inhibitor (Press release, Pfizer, JAN 28, 2022, View Source [SID1234607488]).

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"For more than a decade, Pfizer has worked tirelessly in its pursuit to help transform the trajectory for people living with advanced, biomarker-driven lung cancers," said Andy Schmeltz, Global President & General Manager, Pfizer Oncology. "The European Commission’s approval of LORVIQUA as a first-line therapy is a significant milestone that we hope will help bring a needed and meaningful difference to those impacted by this deadly disease in Europe."

The approval for the first-line use of LORVIQUA was based on the results of the pivotal Phase 3 CROWN trial, in which LORVIQUA reduced the risk of disease progression or death by 72% compared to XALKORI (crizotinib). As a secondary endpoint, the confirmed objective response rate (ORR) was 76% (95% CI, 68 to 83) with LORVIQUA and 58% (95% CI, 49 to 66) with XALKORI. In patients with measurable brain metastases, 82% of patients in the LORVIQUA arm experienced an intracranial response (71% had an intracranial complete response), compared to 23% of XALKORI patients. The CROWN trial is a randomized, open-label, parallel 2-arm trial in which 296 people with previously untreated advanced ALK-positive NSCLC were randomized 1:1 to receive LORVIQUA monotherapy (n=149) or XALKORI monotherapy (n=147).

"The expanded approval for LORVIQUA in Europe is a considerable advancement – especially for the close to 40 percent of patients with ALK-positive metastatic NSCLC who are faced with brain metastases at diagnosis," said Professor Benjamin Solomon, MBBS, PhD., Department of Medical Oncology at the Peter MacCallum Cancer Centre in Melbourne, Australia. "It is exciting to see the significant data generated from the CROWN trial continuing to support expanded use around the world and providing physicians in Europe with a highly effective option from the onset of their patients’ treatment journey."

The EC approval of LORVIQUA follows a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) in December 2021. LORVIQUA is approved in the U.S. by the Food and Drug Administration (FDA) under the brand name LORBRENA for the treatment of adults with metastatic NSCLC whose tumors are ALK-positive as detected by an FDA-approved test. In 2019, the EC granted conditional marketing authorization for LORVIQUA as a monotherapy for the treatment of adult patients with ALK-positive advanced NSCLC whose disease has progressed after alectinib or ceritinib as the first ALK tyrosine kinase inhibitor (TKI) therapy, or crizotinib and at least one other ALK TKI.

About the CROWN Trial of LORVIQUA

In the CROWN trial, patients were required to have an ECOG performance status of 0-2 and ALK-positive NSCLC as identified by the VENTANA ALK (D5F3) CDx assay. The primary endpoint of the CROWN trial was progression-free survival (PFS) based on blinded independent central review (BICR). Secondary endpoints included overall survival (OS) and tumor assessment related data by BICR, including ORR, and duration of response (DOR). In patients with measurable central nervous system (CNS) metastases at baseline, additional outcome measures were intracranial (IC)-ORR and IC-DOR by BICR. The trial is continuing in order to further evaluate the secondary endpoint of OS, which was not mature at the time of analysis.

Overall, the safety profile of LORVIQUA was similar to that reported in previous studies. The most frequent adverse events (AEs) in ≥20% of 149 patients treated with LORVIQUA were edema, weight gain, peripheral neuropathy, cognitive effects, diarrhea, dyspnea and hypertriglyceridemia. Serious AEs occurred in 34% of people treated with LORVIQUA; the most frequently reported serious AEs were pneumonia, dyspnea, respiratory failure, cognitive effects and pyrexia. Fatal AEs occurred in 3.4% of people treated with LORVIQUA. Permanent discontinuation of LORVIQUA due to AEs occurred in 6.7% of people. Detailed results from the CROWN study were published in the November 2020 issue of the New England Journal of Medicine.

About Non-Small Cell Lung Cancer (NSCLC)

Lung cancer is the number one cause of cancer-related death around the world.1 NSCLC accounts for approximately 80-85% of lung cancers,2 with ALK-positive tumors occurring in about 3-5% of NSCLC cases.3 Up to 40% of people with ALK-positive metastatic NSCLC present with brain metastases at initial diagnosis.4,5,6

About LORVIQUA (lorlatinib)

LORVIQUA is a TKI that has been shown to be highly active in preclinical lung cancer models harboring chromosomal rearrangements of ALK. LORVIQUA was specifically developed to inhibit tumor mutations that drive resistance to other ALK inhibitors and to penetrate the blood brain barrier.

The full U.S. prescribing information for LORBRENA can be found here.

IMPORTANT LORBRENA (lorlatinib) SAFETY INFORMATION FROM THE U.S. PRESCRIBING INFORMATION

Contraindications: LORBRENA is contraindicated in patients taking strong CYP3A inducers, due to the potential for serious hepatotoxicity.

Risk of Serious Hepatotoxicity with Concomitant Use of Strong CYP3A Inducers: Severe hepatotoxicity occurred in 10 of 12 healthy subjects receiving a single dose of LORBRENA with multiple daily doses of rifampin, a strong CYP3A inducer. Grade 4 ALT or AST elevations occurred in 50% of subjects, Grade 3 in 33% of subjects, and Grade 2 in 8% of subjects. ALT or AST elevations occurred within 3 days and returned to within normal limits after a median of 15 days (7 to 34 days); median time to recovery in subjects with Grade 3 or 4 or Grade 2 ALT or AST elevations was 18 days and 7 days, respectively. LORBRENA is contraindicated in patients taking strong CYP3A inducers. Discontinue strong CYP3A inducers for 3 plasma half-lives of the strong CYP3A inducer prior to initiating LORBRENA.

Central Nervous System (CNS) Effects: A broad spectrum of CNS effects can occur; overall, CNS effects occurred in 52% of the 476 patients receiving LORBRENA. These included seizures (1.9%, sometimes in conjunction with other neurologic findings), psychotic effects (7%; 0.6% severe [Grade 3 or 4]), and changes in cognitive function (28%; 2.9% severe), mood (including suicidal ideation) (21%; 1.7% severe), speech (11%; 0.6% severe), mental status (1.3%; 1.1% severe), and sleep (12%). Median time to first onset of any CNS effect was 1.4 months (1 day to 3.4 years). Overall, 2.1% and 10% of patients required permanent or temporary discontinuation of LORBRENA, respectively, for a CNS effect; 8% required dose reduction. Withhold and resume at same or reduced dose or permanently discontinue based on severity.

Hyperlipidemia: Increases in serum cholesterol and triglycerides can occur. Grade 3 or 4 elevations in total cholesterol occurred in 18% and Grade 3 or 4 elevations in triglycerides occurred in 19% of the 476 patients who received LORBRENA. Median time to onset was 15 days for both hypercholesterolemia and hypertriglyceridemia. Approximately 4% and 7% of patients required temporary discontinuation and 1% and 3% of patients required dose reduction of LORBRENA for elevations in cholesterol and in triglycerides in Study B7461001 and Study B7461006, respectively. Eighty-three percent of patients required initiation of lipid-lowering medications, with a median time to onset of start of such medications of 17 days. Initiate or increase the dose of lipid-lowering agents in patients with hyperlipidemia. Monitor serum cholesterol and triglycerides before initiating LORBRENA, 1 and 2 months after initiating LORBRENA, and periodically thereafter. Withhold and resume at same dose for the first occurrence; resume at same or reduced dose of LORBRENA for recurrence based on severity.

Atrioventricular (AV) Block: PR interval prolongation and AV block can occur. In 476 patients who received LORBRENA at a dose of 100 mg orally once daily and who had a baseline electrocardiography (ECG), 1.9% experienced AV block and 0.2% experienced Grade 3 AV block and underwent pacemaker placement. Monitor ECG prior to initiating LORBRENA and periodically thereafter. Withhold and resume at reduced or same dose in patients who undergo pacemaker placement. Permanently discontinue for recurrence in patients without a pacemaker.

Interstitial Lung Disease (ILD)/Pneumonitis: Severe or life-threatening pulmonary adverse reactions consistent with ILD/pneumonitis can occur. ILD/pneumonitis occurred in 1.9% of patients, including Grade 3 or 4 ILD/pneumonitis in 0.6% of patients. Four patients (0.8%) discontinued LORBRENA for ILD/pneumonitis. Promptly investigate for ILD/pneumonitis in any patient who presents with worsening of respiratory symptoms indicative of ILD/pneumonitis (e.g., dyspnea, cough, and fever). Immediately withhold LORBRENA in patients with suspected ILD/pneumonitis. Permanently discontinue LORBRENA for treatment-related ILD/pneumonitis of any severity.

Hypertension: Hypertension can occur. Hypertension occurred in 13% of patients, including Grade 3 or 4 in 6% of patients. Median time to onset of hypertension was 6.4 months (1 day to 2.8 years), and 2.3% of patients temporarily discontinued LORBRENA for hypertension. Control blood pressure prior to initiating LORBRENA. Monitor blood pressure after 2 weeks and at least monthly thereafter. Withhold and resume at reduced dose or permanently discontinue based on severity.

Hyperglycemia: Hyperglycemia can occur. Hyperglycemia occurred in 9% of patients, including Grade 3 or 4 in 3.2% of patients. Median time to onset of hyperglycemia was 4.8 months (1 day to 2.9 years), and 0.8% of patients temporarily discontinued LORBRENA for hyperglycemia. Assess fasting serum glucose prior to initiating LORBRENA and monitor periodically thereafter. Withhold and resume at reduced dose or permanently discontinue based on severity.

Embryo-fetal Toxicity: LORBRENA can cause fetal harm. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use an effective non-hormonal method of contraception, since LORBRENA can render hormonal contraceptives ineffective, during treatment with LORBRENA and for at least 6 months after the final dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with LORBRENA and for 3 months after the final dose.

Adverse Reactions: In the pooled safety population of 476 patients who received 100 mg LORBRENA once daily, the most frequent (≥ 20%) adverse reactions were edema (56%), peripheral neuropathy (44%), weight gain (31%), cognitive effects (28%), fatigue (27%), dyspnea (27%), arthralgia (24%), diarrhea (23%), mood effects (21%), and cough (21%). The most frequent (≥ 20%) Grade 3-4 laboratory abnormalities in patients receiving LORBRENA were hypercholesterolemia (21%) and hypertriglyceridemia (21%).

In previously untreated patients, serious adverse reactions occurred in 34% of the 149 patients treated with LORBRENA; the most frequently reported serious adverse reactions were pneumonia (4.7%), dyspnea (2.7%), respiratory failure (2.7%), cognitive effects (2.0%), and pyrexia (2.0%). Fatal adverse reactions occurred in 3.4% of patients and included pneumonia (0.7%), respiratory failure (0.7%), cardiac failure acute (0.7%), pulmonary embolism (0.7%), and sudden death (0.7%). In the Phase 1/2 study, serious adverse reactions occurred in 32% of the 295 patients; the most frequently reported serious adverse reactions were pneumonia (3.4%), dyspnea (2.7%), pyrexia (2%), mental status changes (1.4%), and respiratory failure (1.4%). Fatal adverse reactions occurred in 2.7% of patients and included pneumonia (0.7%), myocardial infarction (0.7%), acute pulmonary edema (0.3%), embolism (0.3%), peripheral artery occlusion (0.3%), and respiratory distress (0.3%).

Drug Interactions: LORBRENA is contraindicated in patients taking strong CYP3A inducers. Avoid concomitant use with moderate CYP3A inducers, strong CYP3A inhibitors, and fluconazole. If concomitant use of moderate CYP3A inducers cannot be avoided, increase the LORBRENA dose as recommended. If concomitant use with a strong CYP3A inhibitor or fluconazole cannot be avoided, reduce the LORBRENA dose as recommended. Avoid concomitant use of LORBRENA with CYP3A substrates and P-gp substrates, which may reduce the efficacy of these substrates.

Lactation: Because of the potential for serious adverse reactions in breastfed infants, instruct women not to breastfeed during treatment with LORBRENA and for 7 days after the final dose.

Hepatic Impairment: No dose adjustment is recommended for patients with mild hepatic impairment. The recommended dose of LORBRENA has not been established for patients with moderate or severe hepatic impairment.

Renal Impairment: Reduce the dose of LORBRENA for patients with severe renal impairment. No dose adjustment is recommended for patients with mild or moderate renal impairment.

On January 28, 2022 Eczacıbaşı-Monrol Nuclear Products Co. (Monrol) has reported it has signed an agreement with Curium Netherlands B.V (Curium) to license its GMP grade medical radioisotope, no-carrier-added 177Lu (n.c.a. 177Lu) cutting-edge production technology LuMagic (Press release, Eczacıbaşı-Monrol Nuclear Products, JAN 28, 2022, View Source [SID1234607487]). This agreement will enable transfer of relevant equipment and supply from Monrol to Curium.

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Monrol is one of the few producers of Lutetium-177 n.c.a worldwide, having uninterrupted worldwide supply capabilities. Monrol Lu-177 n.c.a production process is an exclusive processing technology having cleaner and safer production method with stable isotope enrichment capability. Curium planning to manufacture the product Lu-177 n.c.a in its Petten production facility, Netherlands. This licence is offering significant opportunities both for Curium; one of the world’s largest nuclear medicine companies and Monrol; a company which develops, manufactures, and distributes world-class radiopharmaceutical products, radioisotopes to improve quality of life of cancer patients globally.

Lutetium-177 n.c.a is a radioisotope of choice for targeted radionuclide therapy. Lu-177 n.c.a production process enables treatment options that have the potential to improve treatment outcomes for certain cancer patients today and more potential treatment options in future under clinical development. Unique properties of Lutetium-177 n.c.a makes it a theranostically desirable radioisotope for peptide receptor radionuclide therapy (PRRT) to treat certain cancers like Neuro Endocrine Tumors (NET) and Prostate cancer.

In line with our mission to improve the quality of life of cancer patients globally, Monrol is establishing strategic partnerships with multinational pharmaceutical companies and constructing a new production facility compliant with FDA 21 CFR Part 211 quality standards which will have an annual production capacity of 60 thousand doses. With its location close to Istanbul’s transportation hub, the new facility will benefit from a worldwide logistics network and agreements with cargo services to 320 destinations worldwide.

"Lu-177 n.c.a contributes to our mission to improve quality of life of cancer patients globally. Our new GMP certified facility exclusively designed for theranostic R&D and production with cutting edge technology will enable us to maximize supply of high-quality Lutetium. We are committed to working closely with Curium to potentially bring new therapeutic radiopharmaceutical agents into market soon to improve patients’ lives having life threatening diseases" said Monrol General Manager Aydın Kucuk".

John Sylvester CEO of Curium’s SPECT and International businesses commented "We are delighted with Monrol as a technology partner, after extensive benchmarking this technology gave both the highest quality product with the most efficient process, as it is already proven and ‘plug and play’ in nature the time to market will be very short".

On January 28, 2022 BeiGene (NASDAQ: BGNE; HKEX: 06160; SSE: 688235), a global, science-driven biotechnology company focused on developing innovative and affordable medicines, reported that the Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA) has accepted a supplemental new drug application (sNDA) for BeiGene’s BTK inhibitor BRUKINSA (zanubrutinib) as a treatment for adult patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) and granted BRUKINSA breakthrough therapy designation (BTD) (Press release, BeiGene, JAN 28, 2022, View Source [SID1234607486]).

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"This is BRUKINSA’s first filing in treatment-naïve CLL supported by the positive global Phase 3 SEQUOIA trial, a remarkable step forward in its global registration program. As presented at ASH (Free ASH Whitepaper), BRUKINSA significantly prolonged progression-free survival and was generally well-tolerated in these patients, with demonstrated superiority over chemoimmunotherapy in the SEQUOIA trial," commented Jane Huang, M.D., Chief Medical Officer of Hematology at BeiGene. "Together with the filing in Waldenström’s macroglobulinemia, we are hoping to expand the clinical use of this potential best-in-class BTK inhibitor from relapsed or refractory setting to frontline care for the blood cancer community in China."

The sNDA is supported by clinical results from the randomized, multicenter, global Phase 3 SEQUOIA trial (NCT03336333) comparing BRUKINSA to bendamustine in combination with rituximab (B+R) in patients with treatment-naïve CLL.

As assessed by an independent review committee (IRC), BRUKINSA demonstrated superiority in progression-free survival (PFS) over B+R. With a median follow-up of 26.15 months, the 24-month PFS was 85.5% (95% CI: 80.1, 89.6) with BRUKINSA, compared to 69.5% (95% CI: 62.4, 75.5) with B+R, and the hazard ratio (HR) was 0.42 (95% CI: 0.27, 0.63), p<0.0001. BRUKINSA was generally well tolerated with a safety profile consistent with its broad clinical program, including a low rate of atrial fibrillation.

About Chronic Lymphocytic Leukemia

Chronic lymphocytic leukemia (CLL) is the most common form of leukemia in adults, with a global incidence of approximately 114,000 new cases in 2017. CLL affects white blood cells or lymphocytes in the bone marrow, Proliferation of cancer cells (leukemia) in the marrow result in reduced ability to fight infection and spread into the blood, which affects other parts of the body including the lymph nodes, liver and spleen.1,2,3 The BTK pathway is a known route that signals malignant B cells and contributes to the onset of CLL.4 Small lymphocytic lymphoma (SLL) is a non-Hodgkin’s lymphoma affecting the B-lymphocytes of the immune system, which shares many similarities to CLL but with cancer cells found mostly in lymph nodes.5

About BRUKINSA

BRUKINSA is a small molecule inhibitor of Bruton’s tyrosine kinase (BTK) discovered by BeiGene scientists that is currently being evaluated globally in a broad clinical program as a monotherapy and in combination with other therapies to treat various B-cell malignancies. Because new BTK is continuously synthesized, BRUKINSA was specifically designed to deliver complete and sustained inhibition of the BTK protein by optimizing bioavailability, half-life, and selectivity. With differentiated pharmacokinetics compared to other approved BTK inhibitors, BRUKINSA has been demonstrated to inhibit the proliferation of malignant B cells within a number of disease relevant tissues.

BRUKINSA has received 20 approvals covering 43 countries and regions:

For the treatment of mantle cell lymphoma (MCL) in adult patients who have received at least one prior therapy (United States, November 2019)*;
For the treatment of MCL in adult patients who have received at least one prior therapy (China, June 2020)**;
For the treatment of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) in adult patients who have received at least one prior therapy (China, June 2020)**;
For the treatment of MCL in patients who have received at least one prior therapy (Israel, January 2021);
For the treatment of relapsed or refractory MCL (United Arab Emirates, February 2021);
For the treatment of Waldenström’s macroglobulinemia (WM) in adult patients (Canada, March 2021);
For the treatment of adult patients with WM who have received at least one prior therapy (China, June 2021)**;
For the treatment of MCL in adult patients who have received at least one prior therapy (Canada, July 2021);
For the treatment of MCL in adult patients who have received at least one prior therapy (Chile, July 2021);
For the treatment of adult patients with MCL who have received at least one previous therapy (Brazil, August 2021);
For the treatment of adult patients with WM (United States, August 2021);
For the treatment of adult patients with marginal zone lymphoma (MZL) who have received at least one anti-CD20-based regimen (United States, September 2021)*;
For the treatment of adult patients with MCL who have received at least one previous therapy (Singapore, October 2021);
For the treatment of adult patients with WM who have received at least one prior therapy, or in first line treatment for patients unsuitable for chemo-immunotherapy (Australia, October 2021);
For the treatment of adult patients with MCL who have received at least one prior therapy (Australia, October 2021);
For the treatment of adult patients with MCL who have received at least one previous therapy (Russia, October 2021);
For the treatment of adult patients with MCL who have received at least one previous therapy (Saudi Arabia, November 2021);
For the treatment of adult patients with WM who have received at least one prior therapy or first-line treatment of patients unsuitable for chemo-immunotherapy (European Union plus Iceland, Lichtenstein, and Norway, November 2021);
For the treatment of eligible adult patients with Waldenström’s macroglobulinemia (WM) who have received at least one prior therapy or for the first-line treatment of eligible patients unsuitable for chemo-immunotherapy (Great Britain, December 2021); and
For the treatment of adult patients with MCL who have received at least one previous therapy (Ecuador, December 2021).
To date, more than 20 marketing authorization applications have been submitted for BRUKINSA for various indications.

* This indication was approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

** This indication was approved under conditional approval. Complete approval for this indication may be contingent upon results from ongoing randomized, controlled confirmatory clinical trials.

IMPORTANT U.S. SAFETY INFORMATION FOR BRUKINSA (ZANUBRUTINIB)

Warnings and Precautions

Hemorrhage

Fatal and serious hemorrhagic events have occurred in patients with hematological malignancies treated with BRUKINSA monotherapy. Grade 3 or higher hemorrhage including intracranial and gastrointestinal hemorrhage, hematuria and hemothorax have been reported in 3.4% of patients treated with BRUKINSA monotherapy. Hemorrhage events of any grade occurred in 35% of patients treated with BRUKINSA monotherapy.

Bleeding events have occurred in patients with and without concomitant antiplatelet or anticoagulation therapy. Co-administration of BRUKINSA with antiplatelet or anticoagulant medications may further increase the risk of hemorrhage.

Monitor for signs and symptoms of bleeding. Discontinue BRUKINSA if intracranial hemorrhage of any grade occurs. Consider the benefit-risk of withholding BRUKINSA for 3-7 days pre- and post-surgery depending upon the type of surgery and the risk of bleeding.

Infections

Fatal and serious infections (including bacterial, viral, or fungal) and opportunistic infections have occurred in patients with hematological malignancies treated with BRUKINSA monotherapy. Grade 3 or higher infections occurred in 27% of patients, most commonly pneumonia. Infections due to hepatitis B virus (HBV) reactivation have occurred.

Consider prophylaxis for herpes simplex virus, pneumocystis jiroveci pneumonia and other infections according to standard of care in patients who are at increased risk for infections. Monitor and evaluate patients for fever or other signs and symptoms of infection and treat appropriately.

Cytopenias

Grade 3 or 4 cytopenias, including neutropenia (26%), thrombocytopenia (11%) and anemia (8%) based on laboratory measurements, developed in patients treated with BRUKINSA monotherapy. Grade 4 neutropenia occurred in 13% of patients, and Grade 4 thrombocytopenia occurred in 3.6% of patients.

Monitor complete blood counts regularly during treatment and interrupt treatment, reduce the dose, or discontinue treatment as warranted. Treat using growth factor or transfusions, as needed.

Second Primary Malignancies

Second primary malignancies, including non-skin carcinoma, have occurred in 14% of patients treated with BRUKINSA monotherapy. The most frequent second primary malignancy was non-melanoma skin cancer, reported in 8% of patients. Other second primary malignancies included malignant solid tumors (4.0%), melanoma (1.7%) and hematologic malignancies (1.2%). Advise patients to use sun protection and monitor patients for the development of second primary malignancies.

Cardiac Arrhythmias

Atrial fibrillation and atrial flutter were reported in 3.2% of patients treated with BRUKINSA monotherapy. Patients with cardiac risk factors, hypertension, and acute infections may be at increased risk. Grade 3 or higher events were reported in 1.1% of patients treated with BRUKINSA monotherapy. Monitor signs and symptoms for atrial fibrillation and atrial flutter and manage as appropriate.

Embryo-Fetal Toxicity

Based on findings in animals, BRUKINSA can cause fetal harm when administered to a pregnant woman. Administration of zanubrutinib to pregnant rats during the period of organogenesis caused embryo-fetal toxicity including malformations at exposures that were 5 times higher than those reported in patients at the recommended dose of 160 mg twice daily. Advise women to avoid becoming pregnant while taking BRUKINSA and for 1 week after the last dose. Advise men to avoid fathering a child during treatment and for 1 week after the last dose.

If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus.

Adverse reactions

The most common adverse reactions, including laboratory abnormalities, in ≥ 30% of patients who received BRUKINSA (N = 847) included decreased neutrophil count (54%), upper respiratory tract infection (47%), decreased platelet count (41%), hemorrhage (35%), decreased lymphocyte count (31%), rash (31%) and musculoskeletal pain (30%).

Drug Interactions

CYP3A Inhibitors: When BRUKINSA is co-administered with a strong CYP3A inhibitor, reduce BRUKINSA dose to 80 mg once daily. For coadministration with a moderate CYP3A inhibitor, reduce BRUKINSA dose to 80 mg twice daily.

CYP3A Inducers: Avoid coadministration with moderate or strong CYP3A inducers.

Specific Populations

Hepatic Impairment: The recommended dose of BRUKINSA for patients with severe hepatic impairment is 80 mg orally twice daily.

Please see full U.S. Prescribing Information at www.beigene.com/PDF/BRUKINSAUSPI.pdf and Patient Information at www.beigene.com/PDF/BRUKINSAUSPPI.pdf.

BeiGene Oncology

BeiGene is committed to advancing best- and first-in-class clinical candidates internally or with like-minded partners to develop impactful and affordable medicines for patients across the globe. We have a growing R&D and medical affairs team of approximately 2,900 colleagues dedicated to advancing more than 100 clinical trials that have involved more than 14,500 subjects. Our expansive portfolio is directed predominantly by our internal colleagues supporting clinical trials in more than 45 countries and regions. Hematology-oncology and solid tumor targeted therapies and immuno-oncology are key focus areas for the Company, with both mono- and combination therapies prioritized in our research and development. BeiGene currently has three approved medicines discovered and developed in our own labs: BTK inhibitor BRUKINSA in the United States, China, the EU and U.K., Canada, Australia and additional international markets; and the non-FC-gamma receptor binding anti-PD-1 antibody tislelizumab as well as the PARP inhibitor pamiparib in China.

BeiGene also partners with innovative companies who share our goal of developing therapies to address global health needs. We commercialize a range of oncology medicines in China licensed from Amgen, Bristol Myers Squibb, EUSA Pharma and Bio-Thera. We also plan to address greater areas of unmet need globally through our other collaborations including with Mirati Therapeutics, Seagen, and Zymeworks.

In January 2021 BeiGene and Novartis announced a collaboration granting Novartis rights to co-develop, manufacture, and commercialize BeiGene’s anti-PD1 antibody tislelizumab in North America, Europe, and Japan. Building upon this productive collaboration, including a biologics license application (BLA) under FDA review, BeiGene and Novartis announced an option, collaboration and license agreement in December 2021 for BeiGene’s TIGIT inhibitor ociperlimab that is in Phase 3 development. Novartis and BeiGene also entered into a strategic commercial agreement through which BeiGene will promote five approved Novartis Oncology products across designated regions of China.