CD molecules x TNF-α x TNFR

NANJING, China, March 14, 2023 /PRNewswire/ -- Simcere Pharmaceutical Group Limited (2096.HK) (Simcere), an innovative global biopharmaceutical company, announced today that Simcere Zaiming, an innovative oncology pharmaceutical company of Simcere has entered into a clinical collaboration agreement with MSD (Merck & Co., Inc., Rahway, NJ, USA) to evaluate the combination of SIM0235, a potential first-in-class humanized anti-tumor necrosis factor receptor 2 (TNFR2) monoclonal antibody, and MSD's anti-PD-1 therapy, KEYTRUDA® (pembrolizumab), in patients with advanced solid tumors and cutaneous T-cell lymphoma (CTCL). This is a Phase 1 trial（SIM1811-03-TNFR2-102） to evaluate the safety, efficacy, pharmacokinetic/pharmacodynamic characteristics and immunogenicity of SIM0235 monotherapy and SIM0235 in combination with KEYTRUDA in patients with advanced solid tumors and CTCL. Tumor necrosis factor receptor 2 (TNFR2) is a member of the tumor necrosis factor receptor superfamily and is primarily expressed on the surface of tumor cells and immune suppressive cells in the tumor microenvironment, leading to immune escape and tumor proliferation. "Data generated from preclinical models demonstrate the capability of our potential first-in-class monoclonal antibody, SIM0235, in combination with KEYTRUDA, to clinically benefit patients with these cancers," said Dr. Bijoyesh Mookerjee, M.D., Chief Medical Officer, Oncology, Simcere Pharmaceutical Group. Under the terms of the agreement, MSD will supply KEYTRUDA and collaborate with Simcere Zaiming on this study. Simcere Zaiming retains all worldwide commercial rights to SIM0235. KEYTRUDA® is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. About SIM0235 SIM0235 (SIM1811-03 injection) is an investigational humanized immunoglobulin G1 (IgG1) monoclonal antibody that targets TNFR2 and blocks its activation by endogenous tumor necrosis factor (TNF), inhibiting the immunosuppressive function and proliferation mediated by TNFR2, to enhance the anti-tumor immune response. Additionally, the antibody has shown cytotoxic effect on TNFR2-expressing immune suppressive cells including regulatory T cells (Tregs) and bone marrow-derived suppressor cells via antibody-dependent cell cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). SIM0235 is currently being studied in patients with advanced solid tumors or cutaneous T-cell lymphoma (CTCL) in Phase 1 trials in China (SIM1811-03-TNFR2-101) and the US (SIM1811-03-TNFR2-102). About Simcere Zaiming Simcere Zaiming is an oncology biopharmaceutical company, and a subsidiary of Simcere Pharmaceutical Group Limited, that focuses on the R&D, production and commercialization of innovative cancer therapeutics. The company was formed in 2023 and is committed to solving unmet clinical needs for cancer patients in China and around the world by developing breakthrough treatments. Simcere Zaiming has built an innovative R&D pipeline with differentiated clinical value. In addition to the company's R&D portfolio, Simcere Zaiming has three innovative drugs, COSELA®, Endostar®, and Envafolimab®. By collaborating with partners globally, Simcere Zaiming strives to bring potentially new innovative therapeutics to cancer patients worldwide. About Simcere Pharmaceutical Group Simcere Pharmaceutical Group Limited (2096.HK) is an innovation and R&D-driven pharmaceutical company. The Company focuses on three therapeutic areas, oncology, central nervous system and autoimmune diseases, with a forward-looking vision toward disease areas that may have significant clinical needs in the future, aiming to achieve the mission of "providing today's patients with medicines of the future." Leveraging its R&D capability and commercialization excellence, Simcere has built a market-leading product portfolio in China. Its vigorous in-house R&D efforts and extensive R&D and commercial stage collaborations have made it a strategic alliance partner with world leading innovative companies and research institutes. For more information, please visit: SOURCE Simcere Pharmaceutical Group Limited

New Real-World Evidence Highlights AMGEVITA® Utilization, Treatment Satisfaction and Persistence in European Patients New Data From First-in-Class Treatment TAVNEOS®, Evaluating Renal Function Among Adults Living With Severe Active ANCA-Associated Vasculitis THOUSAND OAKS, Calif., Nov. 7, 2022 /PRNewswire/ -- Amgen (NASDAQ:AMGN) today announced that clinical and real-world data across its broad portfolio of established treatments and pipeline assets will be presented at the annual American College of Rheumatology Convergence (ACR), taking place in Philadelphia on Nov. 10-14, 2022. Among 25 abstracts, noteworthy presentations will include real-world evidence for AMGEVITA®* (adalimumab), underscoring treatment satisfaction and persistence in German patients with rheumatic diseases. Additional data will highlight utilization in European patients with moderate to severe rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis. Other research highlights include data on TAVNEOS® (avacopan) in severe active anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis, notably an oral presentation on evaluation of recovery of renal function among patients with baseline estimated glomerular filtration rate (eGFR) at or below 20; renal function is impaired in the majority of people with the disease. Additionally, two real-world evidence posters report on the effects of Otezla® (apremilast) on cardiometabolic parameters in patients with psoriatic disease. "Given the uptake of biosimilars, we are looking forward to presenting real-world evidence data from the experiences of patients using AMGEVITA, since it was approved in Europe four years ago," said David M. Reese, M.D., executive vice president of Research and Development at Amgen. "The breadth of data being presented reflects our deep commitment to driving innovation in inflammatory diseases." *AMJEVITA™ outside the US is marketed as AMGEVITA. AMJEVITA is currently not available commercially and will not be commercially available in the United States until on or after January 31, 2023. Abstracts and Presentation Times: AMGEVITA® (adalimumab) Abstracts Real-World Utilization of Adalimumab Biosimilar (ABP 501) in Patients with Rheumatoid Arthritis, Ankylosing Spondylitis and Psoriatic Arthritis in Europe Abstract #1387, Virtual Poster Session, Sunday, Nov. 13 from 1-3 p.m. EST Treatment Persistence and Switching Patterns of ABP 501 (AMGEVITA®) in German Patients with Rheumatic Diseases Abstract #1425, Virtual Poster Session, Sunday, Nov. 13 from 1-3 p.m. EST SLE/AMG 592 Abstracts Unmet Need in Systemic Lupus Erythematosus (SLE) Therapy: High Corticosteroid Use and Poor Adherence and Persistence to SLE Treatments in the US Abstract #1275040, Oral Poster Session, Monday, Nov. 14 from 3-4:30 p.m. EST Real-World Treatment Patterns, Healthcare Resource Utilization (HCRU) and Costs in Patients with Systemic Lupus Erythematosus (SLE) in the US Abstract #1274556, Virtual Poster Session, Saturday, Nov. 12 from 1-3 p.m. EST Regulatory T Cell Defects in SLE and Therapy with a Novel IL-2 Mutein: Phase 1 Clinical Results with Efavaleukin Alfa Abstract #0989, Ignite Poster Talk, Monday, Nov.14 from 1-1:55 p.m. EST, Virtual Poster Presentation, Sunday, Nov. 13 from 9-10:30 a.m. EST Enbrel® (etanercept) Abstracts Outcomes of Etanercept and Janus Kinase Inhibitor Treatment After First-line Use of Adalimumab in Patients with Rheumatoid Arthritis Abstracts #1588, Oral Poster Session, Sunday, Nov. 13 from 3-4:30 p.m. EST Lower Healthcare Costs for Commercially Insured Patients with Rheumatoid Arthritis in Remission Abstracts #0060, Virtual Poster Session, Saturday, Nov. 12 from 1-3 p.m. EST Maintenance of Disease Activity and Treatment Persistence in Patients with Rheumatoid Arthritis Who Switched from Combination to TNF inhibitor Monotherapy: Results from the Rheumatology Informatics System for Effectiveness (RISE) Registry Abstracts #0306, Virtual Poster Session, Saturday, Nov. 12 from 1-3 p.m. EST Change in Disease Activity and Occurrence of Adverse Events After Initiation of Etanercept in Pediatric Patients with Juvenile Psoriatic Arthritis in the CARRA Registry Abstracts #1418, Virtual Poster Session, Sunday, Nov. 13 from 1-3 p.m. EST Outcomes in Patients with Rheumatoid Arthritis Initiating Monotherapy with Etanercept, Adalimumab, or Janus Kinase Inhibitors Abstracts #1420, Virtual Poster Session, Sunday, Nov. 13 from 1-3 p.m. EST EVENITY® (romosozumab-aqqg) Abstracts Effect of Romosozumab on Bone Microarchitecture as Assessed by Tissue Thickness-Adjusted Trabecular Bone Score in Postmenopausal Women with Osteoporosis: Results from the ARCH Study Abstract #319 Effect of Romosozumab in Postmenopausal Women with Knee Osteoarthritis: Results from the FRAME Clinical Trial Abstract #1278232, Virtual Poster Session, Sunday, Nov. 13 from 1-3 p.m. EST Otezla® (apremilast) Abstracts Characterization of Joint Distribution and Disease Burden in Patients with Early Oligoarticular Psoriatic Arthritis: Results from the Ongoing FOREMOST Study (EULAR 2022 Encore) Abstract #1289024, Virtual Poster Session, Sunday, Nov. 13 from 9-10:30 a.m. EST Diabetes Burden and Effects of Apremilast on Changes in Cardiometabolic Parameters in Patients with Psoriasis (PsO) or Psoriatic Arthritis (PsA) in a Real-World Setting Abstract #1290834, Virtual Poster Session, Sunday, Nov. 13 from 1-3 p.m. EST Effectiveness by Disease Severity in Patients with Psoriatic Arthritis Treated with Apremilast in the CorEvitas Psoriatic Arthritis/Spondyloarthritis (PsA/SpA) Registry Abstract #1289089, Virtual Poster Session, Sunday, Nov. 13 from 9-10:30 a.m. EST Obesity Burden and Effects of Apremilast on Changes in Cardiometabolic Parameters by Obesity Status in Patients with Psoriasis (PsO) or Psoriatic Arthritis (PsA) in a Real-World Setting Abstract #1291242, Virtual Poster Session, Sunday, Nov. 13 from 1-3 p.m. EST Exposure-Adjusted Incidence Rate for Adverse Events of Special Interest in Patients with Psoriatic Arthritis Treated with Apremilast Abstract #1289316, Virtual Poster Session, Monday, Nov. 14 from 1-3 p.m. EST Similar Improvements in Psoriatic Arthritis Disease Domains with Apremilast Treatment Regardless of Prior Nonsteroidal Anti-inflammatory Drug Use Abstract Insert, N/A Presentation Prolia® (denosumab) Abstracts Comparative Effectiveness of Osteoporosis (OP) Therapies Among a Population of Postmenopausal Women in the United States (U.S.) (Encore) Abstract #1276817, Oral Presentation Session, Sunday, Nov. 13 from 8:30-8:40 a.m. EST Myocardial Infarction and Stroke Risks Among Patients Who Initiated Treatment with Denosumab or Zoledronic Acid for Osteoporosis (Encore) Abstract #1276817, Oral Presentation Session, Sunday, Nov. 13 from 8:15-8:25 a.m. EST Long-term Effect of Denosumab on Bone Microarchitecture as Assessed by Tissue Thickness-Adjusted Trabecular Bone Score (TBS) in Postmenopausal Women with Osteoporosis: Results from the FREEDOM and Open-Label Extension (OLE) (Encore) Abstract Insert, N/A Presentation TAVNEOS® (avacopan) Abstracts Recovery of Renal Function Among ANCA-Associated Vasculitis Patients with Baseline eGFR ≤20 in the Avacopan ADVOCATE Trial Abstract #0525, Oral Presentation Session, Saturday, Nov. 12 from 3:15-3:25 p.m. EST ANCA-Associated Vasculitis Treated with Avacopan versus a Standard Prednisone Taper: Glucocorticoid Toxicity Index Scores by Domain Abstract #1076, Ignite Talk Session, Sunday, Nov. 13 from 10:15-10:20 a.m. EST Safety of Avacopan in ANCA-Associated Vasculitis: Combined Data from Three Clinical Trials Abstract #1077, Ignite Talk Session, Sunday, Nov. 13 from 10:15-10:20 a.m. EST Glucocorticoid Use and Related Adverse Events in ADVOCATE Trial of Avacopan in ANCA-Associated Vasculitis Abstract #1078, Poster Session, Sunday, Nov. 13 from 9-10:30 a.m. EST Abstracts can be found on the ACR website. ABOUT AMJEVITA® (adalimumab-atto) in the U.S. AMJEVITA is a biosimilar to adalimumab, an anti-TNF-α monoclonal antibody. The active ingredient of AMJEVITA is an anti-TNF-α monoclonal antibody that has the same amino acid sequence as, and is highly similar to, adalimumab. AMJEVITA will be delivered in prefilled syringe and autoinjector presentations to support dosing in each of the approved indications. AMJEVITA is not currently available commercially. This not an offer for sale. The following information is derived from the approved label. AMJEVITA is indicated, alone or in combination with methotrexate or other non-biologic DMARDs, for reducing signs and symptoms, inducing major clinical response, inhibiting the progression of structural damage, and improving physical function in adult patients with moderately to severely active rheumatoid arthritis. AMJEVITA is indicated, alone or in combination with methotrexate, for reducing signs and symptoms of moderately to severely active polyarticular juvenile idiopathic arthritis in patients 4 years of age and older. AMJEVITA is indicated, alone or in combination with non-biologic DMARDs, for reducing signs and symptoms, inhibiting the progression of structural damage, and improving physical function in adult patients with active psoriatic arthritis. AMJEVITA is indicated for reducing signs and symptoms in adult patients with active ankylosing spondylitis. AMJEVITA is indicated for reducing signs and symptoms and inducing and maintaining clinical remission in adult patients with moderately to severely active Crohn's disease who have had an inadequate response to conventional therapy, and reducing signs and symptoms and inducing clinical remission in these patients if they have also lost response to or are intolerant to infliximab. AMJEVITA is indicated for inducing and sustaining clinical remission in adult patients with moderately to severely active ulcerative colitis who have had an inadequate response to immunosuppressants such as corticosteroids, azathioprine, or 6-mercaptopurine. The effectiveness of adalimumab products has not been established in patients who have lost response to or were intolerant to TNF blockers. AMJEVITA is indicated for the treatment of adult patients with moderate to severe chronic plaque psoriasis who are candidates for systemic therapy or phototherapy, and when other systemic therapies are medically less appropriate. AMJEVITA should only be administered to patients who will be closely monitored and have regular follow-up visits with a physician. IMPORTANT U.S. SAFETY INFORMATION SERIOUS INFECTIONS Patients treated with AMJEVITA are at increased risk for developing serious infections that may lead to hospitalization or death. Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. Discontinue AMJEVITA if a patient develops a serious infection or sepsis. Reported infections include: Active tuberculosis (TB), including reactivation of latent TB. Patients with TB have frequently presented with disseminated or extrapulmonary disease. Test patients for latent TB before AMJEVITA use and during therapy. Initiate treatment for latent TB prior to AMJEVITA use. Invasive fungal infections, including histoplasmosis, coccidioidomycosis, candidiasis, aspergillosis, blastomycosis, and pneumocystosis. Patients with histoplasmosis or other invasive fungal infections may present with disseminated, rather than localized, disease. Antigen and antibody testing for histoplasmosis may be negative in some patients with active infection. Consider empiric anti-fungal therapy in patients at risk for invasive fungal infections who develop severe systemic illness. Bacterial, viral, and other infections due to opportunistic pathogens, including Legionella and Listeria. Carefully consider the risks and benefits of treatment with AMJEVITA prior to initiating therapy in patients: 1. with chronic or recurrent infection, 2. who have been exposed to TB, 3. with a history of opportunistic infection, 4. who resided in or traveled in regions where mycoses are endemic, 5. with underlying conditions that may predispose them to infection. Monitor patients closely for the development of signs and symptoms of infection during and after treatment with AMJEVITA, including the possible development of TB in patients who tested negative for latent TB infection prior to initiating therapy. Do not start AMJEVITA during an active infection, including localized infections. Patients older than 65 years, patients with co-morbid conditions, and/or patients taking concomitant immunosuppressants may be at greater risk of infection. If an infection develops, monitor carefully and initiate appropriate therapy. Drug interactions with biologic products: A higher rate of serious infections has been observed in rheumatoid arthritis (RA) patients treated with rituximab who received subsequent treatment with a TNF blocker. An increased risk of serious infections has been seen with the combination of TNF blockers with anakinra or abatacept, with no demonstrated added benefit in patients with RA. Concomitant administration of AMJEVITA with other biologic DMARDs (e.g., anakinra or abatacept) or other TNF blockers is not recommended based on the possible increased risk for infections and other potential pharmacological interactions. MALIGNANCY Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with TNF blockers including adalimumab products. Postmarketing cases of hepatosplenic T-cell lymphoma (HSTCL), a rare type of T-cell lymphoma, have been reported in patients treated with TNF blockers including adalimumab products. These cases have had a very aggressive disease course and have been fatal. The majority of reported TNF-blocker cases have occurred in patients with Crohn's disease or ulcerative colitis and the majority were in adolescent and young adult males. Almost all of these patients had received treatment with azathioprine or 6-mercaptopurine concomitantly with a TNF blocker at or prior to diagnosis. It is uncertain whether the occurrence of HSTCL is related to use of a TNF blocker or a TNF blocker in combination with these other immunosuppressants. Consider the risks and benefits of AMJEVITA prior to initiating or continuing therapy in a patient with known malignancy. In clinical trials of some TNF blockers, including adalimumab products, more cases of malignancies were observed among TNF-blocker-treated patients compared to control patients. Non-melanoma skin cancer (NMSC) was reported during clinical trials for adalimumab-treated patients. Examine all patients, particularly those with a history of prolonged immunosuppressant or PUVA therapy, for the presence of NMSC prior to and during treatment with AMJEVITA. In adalimumab clinical trials, there was an approximate 3-fold higher rate of lymphoma than expected in the general U.S. population. Patients with chronic inflammatory diseases, particularly those with highly active disease and/or chronic exposure to immunosuppressant therapies, may be at higher risk of lymphoma than the general population, even in the absence of TNF blockers. Postmarketing cases of acute and chronic leukemia were reported with TNF blocker use. Approximately half of the postmarketing cases of malignancies in children, adolescents, and young adults receiving TNF blockers were lymphomas; other cases included rare malignancies associated with immunosuppression and malignancies not usually observed in children and adolescents. HYPERSENSITIVITY Anaphylaxis and angioneurotic edema have been reported following administration of adalimumab products. If a serious allergic reaction occurs, stop AMJEVITA and institute appropriate therapy. HEPATITIS B VIRUS REACTIVATION Use of TNF blockers, including AMJEVITA, may increase the risk of reactivation of hepatitis B virus (HBV) in patients who are chronic carriers. Some cases have been fatal. Evaluate patients at risk for HBV infection for prior evidence of HBV infection before initiating TNF blocker therapy. Exercise caution in patients who are carriers of HBV and monitor them during and after AMJEVITA treatment. Discontinue AMJEVITA and begin antiviral therapy in patients who develop HBV reactivation. Exercise caution when resuming AMJEVITA after HBV treatment. NEUROLOGIC REACTIONS TNF blockers, including adalimumab products, have been associated with rare cases of new onset or exacerbation of central nervous system and peripheral demyelinating diseases, including multiple sclerosis, optic neuritis, and Guillain-Barré syndrome. Exercise caution when considering AMJEVITA for patients with these disorders; discontinuation of AMJEVITA should be considered if any of these disorders develop. HEMATOLOGICAL REACTIONS Rare reports of pancytopenia, including aplastic anemia, have been reported with TNF blockers. Medically significant cytopenia has been infrequently reported with adalimumab products. Consider stopping AMJEVITA if significant hematologic abnormalities occur. CONGESTIVE HEART FAILURE Worsening or new onset congestive heart failure (CHF) has been reported with TNF blockers. Cases of worsening CHF have been observed with adalimumab products; exercise caution and monitor carefully. AUTOIMMUNITY Treatment with adalimumab products may result in the formation of autoantibodies and, rarely, in development of a lupus-like syndrome. Discontinue treatment if symptoms of a lupus-like syndrome develop. IMMUNIZATIONS Patients on AMJEVITA should not receive live vaccines. Pediatric patients, if possible, should be brought up to date with all immunizations before initiating AMJEVITA therapy. Adalimumab is actively transferred across the placenta during the third trimester of pregnancy and may affect immune response in the in utero exposed infant. The safety of administering live or live-attenuated vaccines in infants exposed to adalimumab products in utero is unknown. Risks and benefits should be considered prior to vaccinating (live or live-attenuated) exposed infants. ADVERSE REACTIONS The most common adverse reactions in adalimumab clinical trials (>10%) were: infections (e.g., upper respiratory, sinusitis), injection site reactions, headache, and rash. Please see full AMJEVITA Prescribing Information , including Medication Guide. INDICATIONS AMJEVITA is indicated, alone or in combination with methotrexate or other non-biologic DMARDs, for reducing signs and symptoms, inducing major clinical response, inhibiting the progression of structural damage, and improving physical function in adult patients with moderately to severely active rheumatoid arthritis. AMJEVITA is indicated, alone or in combination with methotrexate, for reducing signs and symptoms of moderately to severely active polyarticular juvenile idiopathic arthritis in patients 2 years of age and older. AMJEVITA is indicated, alone or in combination with non-biologic DMARDs, for reducing signs and symptoms, inhibiting the progression of structural damage, and improving physical function in adult patients with active psoriatic arthritis. AMJEVITA is indicated for reducing signs and symptoms in adult patients with active ankylosing spondylitis. AMJEVITA is indicated for the treatment of moderately to severely active Crohn's disease in adults and pediatric patients 6 years of age and older. AMJEVITA is indicated for the treatment of moderately to severely active ulcerative colitis in adult patients. The effectiveness of adalimumab products has not been established in patients who have lost response to or were intolerant to TNF blockers. AMJEVITA is indicated for the treatment of adult patients with moderate to severe chronic plaque psoriasis who are candidates for systemic therapy or phototherapy, and when other systemic therapies are medically less appropriate. AMJEVITA should only be administered to patients who will be closely monitored and have regular follow-up visits with a physician. About Systemic Lupus Erythematosus & AMG 592 (efavaleukin alfa) Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease that can impact multiple organ systems. Efavaleukin alfa is an IL-2 mutein Fc fusion protein. It is being investigated for the treatment of inflammatory diseases, including SLE. About ENBREL (etanercept) ENBREL is a soluble form of a tumor necrosis factor (TNF) receptor with a clinical efficacy and safety profile established over 20 years of collective clinical experience. ENBREL was first approved in 1998 for moderate-to-severe rheumatoid arthritis. ENBREL was approved in 1999 to treat moderate-to-severe polyarticular juvenile idiopathic arthritis, in 2002 to treat psoriatic arthritis, in 2003 for the treatment of patients with ankylosing spondylitis, in 2004 to treat moderate-to-severe plaque psoriasis in adults, and in 2016 the moderate-to-severe plaque psoriasis indication was expanded to include patients 4 years or older. Prescription ENBREL is given by injection. ENBREL U.S. Important Safety Information Patients treated with ENBREL are at increased risk for developing serious infections that may lead to hospitalization or death. Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids or were predisposed to infection because of their underlying disease. ENBREL should not be initiated in the presence of sepsis, active infections, or allergy to ENBREL or its components. ENBREL should be discontinued if a patient develops a serious infection or sepsis. Reported infections include: 1) Active tuberculosis (TB), including reactivation of latent TB. Patients with TB have frequently presented with disseminated or extrapulmonary disease. Patients should be tested for latent TB before ENBREL use and periodically during therapy. Treatment for latent infection should be initiated prior to ENBREL use, 2) Invasive fungal infections, including histoplasmosis, coccidioidomycosis, candidiasis, aspergillosis, blastomycosis, and pneumocystosis. Patients with histoplasmosis or other invasive fungal infections may present with disseminated, rather than localized, disease. Antigen and antibody testing for histoplasmosis may be negative in some patients with active infection. Empiric antifungal therapy should be considered in patients at risk for invasive fungal infections who develop severe systemic illness, and 3) Bacterial, viral, and other infections due to opportunistic pathogens, including Legionella and Listeria. The risks and benefits of treatment with ENBREL should be carefully considered prior to initiating therapy in patients 1) with chronic or recurrent infection, 2) who have been exposed to TB, 3) who have resided or traveled in areas of endemic TB or endemic mycoses, or 4) with underlying conditions that may predispose them to infections such as advanced or poorly controlled diabetes. Patients should be closely monitored for the development of signs and symptoms of infection during and after treatment with ENBREL, including the possible development of TB in patients who tested negative for latent TB prior to initiating therapy. Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with tumor necrosis factor (TNF) blockers, including ENBREL. In adult clinical trials of all TNF blockers, more cases of lymphoma were seen compared to control patients. The risk of lymphoma may be up to several-fold higher in RA patients. The role of TNF blocker therapy in the development of malignancies is unknown. Cases of acute and chronic leukemia have been reported in association with postmarketing TNF blocker use in RA and other indications. The risk of leukemia may be higher in patients with RA (approximately 2-fold) than the general population. Melanoma and non-melanoma skin cancer (NMSC) have been reported in patients treated with TNF blockers, including ENBREL. Periodic skin examinations should be considered for all patients at increased risk for skin cancer. In patients who initiated therapy at ≤ 18 years of age, approximately half of the reported malignancies were lymphomas (Hodgkin's and non-Hodgkin's lymphoma). Other cases included rare malignancies usually associated with immunosuppression and malignancies that are not usually observed in children and adolescents. Most of the patients were receiving concomitant immunosuppressants. Treatment with TNF-blocking agents, including ENBREL, has been associated with rare (< 0.1%) cases of new onset or exacerbation of central nervous system demyelinating disorders, some presenting with mental status changes and some associated with permanent disability, and with peripheral nervous system demyelinating disorders. Cases of transverse myelitis, optic neuritis, multiple sclerosis, Guillain-Barré syndromes, other peripheral demyelinating neuropathies, and new onset or exacerbation of seizure disorders have been reported in post marketing experience with ENBREL therapy. Prescribers should exercise caution in considering the use of ENBREL in patients with preexisting or recent-onset central or peripheral nervous system demyelinating disorders. Cases of worsening congestive heart failure (CHF) and, rarely, new-onset cases have been reported in patients taking ENBREL. Caution should be used when using ENBREL in patients with CHF. These patients should be carefully monitored. Rare cases of pancytopenia, including aplastic anemia, some fatal, have been reported. The causal relationship to ENBREL therapy remains unclear. Exercise caution when considering ENBREL in patients who have a previous history of significant hematologic abnormalities. Advise patients to seek immediate medical attention if they develop signs or symptoms of blood dyscrasias or infection. Consider discontinuing ENBREL if significant hematologic abnormalities are confirmed. Reactivation of hepatitis B has been reported in patients who were previously infected with hepatitis B virus (HBV) and received concomitant TNF-blocking agents, including ENBREL. Most reports occurred in patients also taking immunosuppressive agents, which may contribute to hepatitis B reactivation. Exercise caution when considering ENBREL in these patients. Allergic reactions associated with administration of ENBREL during clinical trials have been reported in < 2% of patients. If an anaphylactic reaction or other serious allergic reaction occurs, administration of ENBREL should be discontinued immediately and appropriate therapy initiated. Live vaccines should not be administered to patients on ENBREL. Pediatric patients, if possible, should be brought up to date with all immunizations prior to initiating ENBREL. In patients with exposure to varicella virus, temporarily discontinue ENBREL and consider prophylactic treatment with Varicella Zoster Immune Globulin. Autoantibodies may develop with ENBREL, and rarely lupus-like syndrome or autoimmune hepatitis may occur. These may resolve upon withdrawal of ENBREL. Stop ENBREL if lupus-like syndrome or autoimmune hepatitis develops. The use of ENBREL in patients with Wegener's granulomatosis receiving immunosuppressive agents (e.g., cyclophosphamide) is not recommended. Based on a study of patients treated for alcoholic hepatitis, exercise caution when using ENBREL in patients with moderate-to-severe alcoholic hepatitis. The most commonly reported adverse reactions in RA clinical trials were injection site reaction and infection. In clinical trials of all other adult indications, adverse reactions were similar to those reported in RA clinical trials. In general, the adverse reactions in pediatric patients were similar in frequency and type as those seen in adult patients. The types of infections reported in pediatric patients were generally mild and consistent with those commonly seen in the general pediatric population. The use of ENBREL in patients receiving concurrent cyclophosphamide therapy is not recommended. The risk of serious infection may increase with concomitant use of abatacept therapy. Concurrent therapy with ENBREL and anakinra is not recommended. Hypoglycemia has been reported following initiation of ENBREL therapy in patients receiving medication for diabetes, necessitating a reduction in anti-diabetic medication in some of these patients. Please see ENBREL full Prescribing Information . About EVENITY® (romosozumab-aqqg) EVENITY is a bone-building humanized monoclonal antibody. It is designed to work by inhibiting the activity of sclerostin, which simultaneously results in increased bone formation and to a lesser extent decreased bone resorption. The EVENITY development program includes 19 clinical studies that enrolled more than 14,000 patients. EVENITY has been studied for its potential to reduce the risk of fractures in an extensive global Phase 3 program that included two large fracture trials comparing EVENITY to either placebo or active comparator in nearly 12,000 postmenopausal women with osteoporosis. Amgen and UCB are co-developing EVENITY. EVENITY® U.S. Indication EVENITY® is indicated for the treatment of osteoporosis in postmenopausal women at high risk for fracture, defined as a history of osteoporotic fracture, or multiple risk factors for fracture; or patients who have failed or are intolerant to other available osteoporosis therapy. The anabolic effect of EVENITY® wanes after 12 monthly doses of therapy. Therefore, the duration of EVENITY® use should be limited to 12 monthly doses. If osteoporosis therapy remains warranted, continued therapy with an antiresorptive agent should be considered. EVENITY® Important U.S. Important Safety Information POTENTIAL RISK OF MYOCARDIAL INFARCTION, STROKE AND CARDIOVASCULAR DEATH EVENITY® may increase the risk of myocardial infarction, stroke and cardiovascular death. EVENITY® should not be initiated in patients who have had a myocardial infarction or stroke within the preceding year. Consider whether the benefits outweigh the risks in patients with other cardiovascular risk factors. Monitor for signs and symptoms of myocardial infarction and stroke and instruct patients to seek prompt medical attention if symptoms occur. If a patient experiences a myocardial infarction or stroke during therapy, EVENITY® should be discontinued. In a randomized controlled trial in postmenopausal women, there was a higher rate of major adverse cardiac events (MACE), a composite endpoint of cardiovascular death, nonfatal myocardial infarction and nonfatal stroke, in patients treated with EVENITY® compared to those treated with alendronate. Contraindications: EVENITY® is contraindicated in patients with hypocalcemia. Pre-existing hypocalcemia must be corrected prior to initiating therapy with EVENITY®. EVENITY® is contraindicated in patients with a history of systemic hypersensitivity to romosozumab or to any component of the product formulation. Reactions have included angioedema, erythema multiforme, and urticaria. Hypersensitivity: Hypersensitivity reactions, including angioedema, erythema multiforme, dermatitis, rash, and urticaria have occurred in EVENITY®-treated patients. If an anaphylactic or other clinically significant allergic reaction occurs, initiate appropriate therapy and discontinue further use of EVENITY®. Hypocalcemia: Hypocalcemia has occurred in patients receiving EVENITY®. Correct hypocalcemia prior to initiating EVENITY®. Monitor patients for signs and symptoms of hypocalcemia, particularly in patients with severe renal impairment or receiving dialysis. Adequately supplement patients with calcium and vitamin D while on EVENITY®. Osteonecrosis of the Jaw (ONJ): ONJ, which can occur spontaneously, is generally associated with tooth extraction and/or local infection with delayed healing, and has been reported in patients receiving EVENITY®. A routine oral exam should be performed by the prescriber prior to initiation of EVENITY®. Concomitant administration of drugs associated with ONJ (chemotherapy, bisphosphonates, denosumab, angiogenesis inhibitors, and corticosteroids) may increase the risk of developing ONJ. Other risk factors for ONJ include cancer, radiotherapy, poor oral hygiene, pre-existing dental disease or infection, anemia, and coagulopathy. For patients requiring invasive dental procedures, clinical judgment should guide the management plan of each patient. Patients who are suspected of having or who develop ONJ should receive care by a dentist or an oral surgeon. In these patients, dental surgery to treat ONJ may exacerbate the condition. Discontinuation of EVENITY® should be considered based on benefit-risk assessment. Atypical Femoral Fractures: Atypical low-energy or low trauma fractures of the femoral shaft have been reported in patients receiving EVENITY®. Causality has not been established as these fractures also occur in osteoporotic patients who have not been treated. During EVENITY® treatment, patients should be advised to report new or unusual thigh, hip, or groin pain. Any patient who presents with thigh or groin pain should be evaluated to rule out an incomplete femur fracture. Interruption of EVENITY® therapy should be considered based on benefit-risk assessment. Adverse Reactions: The most common adverse reactions (≥ 5%) reported with EVENITY® were arthralgia and headache. EVENITY® is a humanized monoclonal antibody. As with all therapeutic proteins, there is potential for immunogenicity. Please see EVENITY® full Prescribing Information , including Medication Guide. About Otezla® (apremilast) Otezla® (apremilast) is an oral small-molecule inhibitor of phosphodiesterase 4 (PDE4) specific for cyclic adenosine monophosphate (cAMP). PDE4 inhibition results in increased intracellular cAMP levels, which is thought to indirectly modulate the production of inflammatory mediators. The specific mechanism(s) by which Otezla exerts its therapeutic action in patients is not well defined. Since its initial FDA approval in 2014, Otezla has been prescribed to more than 700,000 patients worldwide. Otezla® (apremilast) U.S. INDICATIONS Otezla® (apremilast) is indicated for the treatment of adult patients with plaque psoriasis who are candidates for phototherapy or systemic therapy. Otezla is indicated for the treatment of adult patients with active psoriatic arthritis. Otezla is indicated for the treatment of adult patients with oral ulcers associated with Behçet's Disease. Otezla® (apremilast) U.S. IMPORTANT SAFETY INFORMATION Contraindications Otezla is contraindicated in patients with a known hypersensitivity to apremilast or to any of the excipients in the formulation Warnings and Precautions Hypersensitivity reactions: Hypersensitivity reactions, including angioedema and anaphylaxis, have been reported during postmarketing surveillance. If signs or symptoms of serious hypersensitivity reactions occur, discontinue Otezla and institute appropriate therapy Diarrhea, Nausea, and Vomiting: Cases of severe diarrhea, nausea, and vomiting were associated with the use of Otezla. Most events occurred within the first few weeks of treatment. In some cases, patients were hospitalized. Patients 65 years of age or older and patients taking medications that can lead to volume depletion or hypotension may be at a higher risk of complications from severe diarrhea, nausea, or vomiting. Monitor patients who are more susceptible to complications of diarrhea or vomiting; advise patients to contact their healthcare provider. Consider Otezla dose reduction or suspension if patients develop severe diarrhea, nausea, or vomiting Depression: Carefully weigh the risks and benefits of treatment with Otezla for patients with a history of depression and/or suicidal thoughts/behavior, or in patients who develop such symptoms while on Otezla. Patients, caregivers, and families should be advised of the need to be alert for the emergence or worsening of depression, suicidal thoughts or other mood changes, and they should contact their healthcare provider if such changes occur Plaque Psoriasis: Treatment with Otezla is associated with an increase in depression. During clinical trials in patients with moderate to severe plaque psoriasis, 1.3% (12/920) of patients reported depression compared to 0.4% (2/506) on placebo. Depression was reported as serious in 0.1% (1/1308) of patients exposed to Otezla, compared to none in placebo-treated patients (0/506). Suicidal behavior was observed in 0.1% (1/1308) of patients on Otezla, compared to 0.2% (1/506) on placebo. One patient treated with Otezla attempted suicide; one patient on placebo committed suicide Psoriatic Arthritis: Treatment with Otezla is associated with an increase in depression. During clinical trials, 1.0% (10/998) reported depression or depressed mood compared to 0.8% (4/495) treated with placebo. Suicidal ideation and behavior was observed in 0.2% (3/1441) of patients on Otezla, compared to none in placebo-treated patients. Depression was reported as serious in 0.2% (3/1441) of patients exposed to Otezla, compared to none in placebo-treated patients (0/495). Two patients who received placebo committed suicide compared to none on Otezla Behçet's Disease: Treatment with Otezla is associated with an increase in depression. During the clinical trial, 1% (1/104) reported depression or depressed mood compared to 1% (1/103) treated with placebo. No instances of suicidal ideation or behavior were reported in patients treated with Otezla or treated with placebo Weight Decrease: Monitor body weight regularly; evaluate unexplained or clinically significant weight loss, and consider discontinuation of Otezla Plaque Psoriasis: Body weight loss of 5-10% occurred in 12% (96/784) of patients with moderate to severe plaque psoriasis treated with Otezla and in 5% (19/382) of patients treated with placebo. Body weight loss of ≥10% occurred in 2% (16/784) of patients treated with Otezla compared to 1% (3/382) of patients treated with placebo Psoriatic Arthritis: Body weight loss of 5-10% was reported in 10% (49/497) of patients taking Otezla and in 3.3% (16/495) of patients taking placebo Behçet's Disease: Body weight loss of >5% was reported in 4.9% (5/103) of patients taking Otezla and in 3.9% (4/102) of patients taking placebo Drug Interactions: Apremilast exposure was decreased when Otezla was co-administered with rifampin, a strong CYP450 enzyme inducer; loss of Otezla efficacy may occur. Concomitant use of Otezla with CYP450 enzyme inducers (e.g., rifampin, phenobarbital, carbamazepine, phenytoin) is not recommended Adverse Reactions Plaque Psoriasis: The most common adverse reactions (≥ 5%) are diarrhea, nausea, upper respiratory tract infection, and headache, including tension headache. Overall, the safety profile of Otezla in patients with mild to moderate plaque psoriasis was consistent with the safety profile previously established in adult patients with moderate to severe plaque psoriasis Psoriatic Arthritis: The most common adverse reactions (≥ 5%) are diarrhea, nausea, and headache Behçet's Disease: The most common adverse reactions (≥ 10%) are diarrhea, nausea, headache, and upper respiratory tract infection. Use in Specific Populations Otezla has not been studied in pregnant women. Advise pregnant women of the potential risk of fetal loss. Please see Otezla full Prescribing Information . About Prolia® (denosumab) Prolia is the first approved therapy that specifically targets RANK Ligand, an essential regulator of bone-removing cells (osteoclasts). Prolia is approved and marketed in over 80 countries worldwide. Prolia® U.S. Indications Prolia® is indicated for the treatment of postmenopausal women with osteoporosis at high risk for fracture, defined as a history of osteoporotic fracture, or multiple risk factors for fracture; or patients who have failed or are intolerant to other available osteoporosis therapy. In postmenopausal women with osteoporosis, Prolia® reduces the incidence of vertebral, nonvertebral, and hip fractures. Prolia® is indicated for treatment to increase bone mass in men with osteoporosis at high risk for fracture, defined as a history of osteoporotic fracture, or multiple risk factors for fracture; or patients who have failed or are intolerant to other available osteoporosis therapy. Prolia® is indicated for the treatment of glucocorticoid-induced osteoporosis in men and women at high risk of fracture who are either initiating or continuing systemic glucocorticoids in a daily dosage equivalent to 7.5 mg or greater of prednisone and expected to remain on glucocorticoids for at least 6 months. High risk of fracture is defined as a history of osteoporotic fracture, multiple risk factors for fracture, or patients who have failed or are intolerant to other available osteoporosis therapy. Prolia® is indicated as a treatment to increase bone mass in men at high risk for fracture receiving androgen deprivation therapy for nonmetastatic prostate cancer. In these patients Prolia® also reduced the incidence of vertebral fractures. Prolia® is indicated as a treatment to increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer. Prolia® U.S. Important Safety Information Contraindications Prolia® is contraindicated in patients with hypocalcemia. Pre–existing hypocalcemia must be corrected prior to initiating Prolia®. Prolia® is contraindicated in women who are pregnant and may cause fetal harm. In women of reproductive potential, pregnancy testing should be performed prior to initiating treatment with Prolia®. Prolia® is contraindicated in patients with a history of systemic hypersensitivity to any component of the product. Reactions have included anaphylaxis, facial swelling and urticaria. Same Active Ingredient Prolia® contains the same active ingredient (denosumab) found in XGEVA®. Patients receiving Prolia® should not receive XGEVA® Hypersensitivity Clinically significant hypersensitivity including anaphylaxis has been reported with Prolia®. Symptoms have included hypotension, dyspnea, throat tightness, facial and upper airway edema, pruritus, and urticaria. If an anaphylactic or other clinically significant allergic reaction occurs, initiate appropriate therapy and discontinue further use of Prolia®. Hypocalcemia Hypocalcemia may worsen with the use of Prolia®, especially in patients with severe renal impairment. In patients predisposed to hypocalcemia and disturbances of mineral metabolism, including treatment with other calcium-lowering drugs, clinical monitoring of calcium and mineral levels is highly recommended within 14 days of Prolia® injection. Concomitant use of calcimimetic drugs may worsen hypocalcemia risk and serum calcium should be closely monitored. Adequately supplement all patients with calcium and vitamin D. Osteonecrosis of the Jaw (ONJ) ONJ, which can occur spontaneously, is generally associated with tooth extraction and/or local infection with delayed healing, and has been reported in patients receiving Prolia®. An oral exam should be performed by the prescriber prior to initiation of Prolia®. A dental examination with appropriate preventive dentistry is recommended prior to treatment in patients with risk factors for ONJ such as invasive dental procedures, diagnosis of cancer, concomitant therapies (e.g., chemotherapy, corticosteroids, angiogenesis inhibitors), poor oral hygiene, and co-morbid disorders. Good oral hygiene practices should be maintained during treatment with Prolia®. The risk of ONJ may increase with duration of exposure to Prolia®. For patients requiring invasive dental procedures, clinical judgment should guide the management plan of each patient. Patients who are suspected of having or who develop ONJ should receive care by a dentist or an oral surgeon. Extensive dental surgery to treat ONJ may exacerbate the condition. Discontinuation of Prolia® should be considered based on individual benefit-risk assessment. Atypical Femoral Fractures Atypical low-energy, or low trauma fractures of the shaft have been reported in patients receiving Prolia®. Causality has not been established as these fractures also occur in osteoporotic patients who have not been treated with antiresorptive agents. During Prolia® treatment, patients should be advised to report new or unusual thigh, hip, or groin pain. Any patient who presents with thigh or groin pain should be evaluated to rule out an incomplete femur fracture. Interruption of Prolia® therapy should be considered, pending a risk/benefit assessment, on an individual basis. Multiple Vertebral Fractures (MVF) Following Discontinuation of Prolia® Treatment Following discontinuation of Prolia® treatment, fracture risk increases, including the risk of multiple vertebral fractures. New vertebral fractures occurred as early as 7 months (on average 19 months) after the last dose of Prolia®. Prior vertebral fracture was a predictor of multiple vertebral fractures after Prolia® discontinuation. Evaluate an individual's benefit/risk before initiating treatment with Prolia®. If Prolia® treatment is discontinued, patients should be transitioned to an alternative antiresorptive therapy. Serious Infections In a clinical trial (N= 7808) in women with postmenopausal osteoporosis, serious infections leading to hospitalization were reported more frequently in the Prolia® group than in the placebo group. Serious skin infections, as well as infections of the abdomen, urinary tract and ear were more frequent in patients treated with Prolia®. Endocarditis was also reported more frequently in Prolia®-treated patients. The incidence of opportunistic infections and the overall incidence of infections were similar between the treatment groups. Advise patients to seek prompt medical attention if they develop signs or symptoms of severe infection, including cellulitis. Patients on concomitant immunosuppressant agents or with impaired immune systems may be at increased risk for serious infections. In patients who develop serious infections while on Prolia®, prescribers should assess the need for continued Prolia® therapy. Dermatologic Adverse Reactions In the same clinical trial in women with postmenopausal osteoporosis, epidermal and dermal adverse events such as dermatitis, eczema and rashes occurred at a significantly higher rate with Prolia® compared to placebo. Most of these events were not specific to the injection site. Consider discontinuing Prolia® if severe symptoms develop. Musculoskeletal Pain Severe and occasionally incapacitating bone, joint, and/or muscle pain has been reported in patients taking Prolia®. Consider discontinuing use if severe symptoms develop. Suppression of Bone Turnover In clinical trials in women with postmenopausal osteoporosis, Prolia® resulted in significant suppression of bone remodeling as evidenced by markers of bone turnover and bone histomorphometry. The significance of these findings and the effect of long-term treatment are unknown. Monitor patients for these consequences, including ONJ, atypical fractures, and delayed fracture healing. Adverse Reactions The most common adverse reactions (>5% and more common than placebo) in women with postmenopausal osteoporosis are back pain, pain in extremity, musculoskeletal pain, hypercholesterolemia, and cystitis. The most common adverse reactions (> 5% and more common than placebo) in men with osteoporosis are back pain, arthralgia, and nasopharyngitis. Pancreatitis has been reported with Prolia®. In women with postmenopausal osteoporosis, the overall incidence of new malignancies was 4.3% in the placebo group and 4.8% in the Prolia® group. In men with osteoporosis, new malignancies were reported in no patients in the placebo group and 4 (3.3%) patients in the Prolia® group. A causal relationship to drug exposure has not been established. The most common adverse reactions (> 3% and more common than active-control group) in patients with glucocorticoid-induced osteoporosis are back pain, hypertension, bronchitis, and headache. The most common (per patient incidence ≥ 10%) adverse reactions reported with Prolia® in patients with bone loss receiving ADT for prostate cancer or adjuvant AI therapy for breast cancer are arthralgia and back pain. Pain in extremity and musculoskeletal pain have also been reported in clinical trials. Additionally, in Prolia®–treated men with nonmetastatic prostate cancer receiving ADT, a greater incidence of cataracts was observed. Denosumab is a human monoclonal antibody. As with all therapeutic proteins, there is potential for immunogenicity. Please see full Prolia® Prescribing Information , including Medication Guide. About TAVNEOS® (avacopan) TAVNEOS (avacopan), approved by the FDA as an adjunctive treatment for adults with severe active ANCA-associated vasculitis, is a first-in-class, orally administered small molecule that employs a novel, highly targeted mode of action in complement-driven autoimmune and inflammatory diseases. While the precise mechanism in ANCA-associated vasculitis has not been definitively established, TAVNEOS, by blocking the complement 5a receptor (C5aR) for the pro-inflammatory complement system fragment known as C5a on destructive inflammatory cells such as blood neutrophils, is presumed to arrest the ability of those cells to do damage in response to C5a activation, which is known to be the driver of ANCA-associated vasculitis. U.S. PRESCRIBING INFORMATION TAVNEOS (avacopan) is indicated as an adjunctive treatment of adult patients with severe active anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (granulomatosis with polyangiitis [GPA] and microscopic polyangiitis [MPA]) in combination with standard therapy including glucocorticoids. TAVNEOS does not eliminate glucocorticoid use. IMPORTANT U.S. SAFETY INFORMATION Contraindications: Serious hypersensitivity to avacopan or to any of the excipients Warning and Precautions Hepatotoxicity: Serious cases of hepatic injury have been observed in patients taking TAVNEOS, including life-threatening events. Obtain liver test panel before initiating TAVNEOS, every 4 weeks after start of therapy for six months and as clinically indicated thereafter. Monitor patients closely for hepatic adverse reactions, and consider pausing or discontinuing treatment as clinically indicated (refer to section 5.1 of the Prescribing Information). TAVNEOS is not recommended for patients with active, untreated and/or uncontrolled chronic liver disease (e.g., chronic active hepatitis B, untreated hepatitis C, uncontrolled autoimmune hepatitis) and cirrhosis. Consider the risk and benefit before administering this drug to a patient with liver disease. Serious Hypersensitivity Reactions: Cases of angioedema occurred in a clinical trial, including one serious event requiring hospitalization. Discontinue immediately if angioedema occurs and manage accordingly. TAVNEOS must not be re-administered unless another cause has been established. Hepatitis B Virus (HBV) Reactivation: Hepatitis B reactivation, including life threatening hepatitis B, was observed in the clinical program. Screen patients for HBV. For patients with evidence of prior infection, consult with physicians with expertise in HBV and monitor during TAVNEOS therapy and for six months following. If patients develop HBV reactivation, immediately discontinue TAVNEOS and concomitant therapies associated with HBV reactivation, and consult with experts before resuming. Serious Infections: Serious infections, including fatal infections, have been reported in patients receiving TAVNEOS. The most common serious infections reported in TAVNEOS group were pneumonia and urinary tract infections. Avoid use of TAVNEOS in patients with active, serious infection, including localized infections. Consider the risks and benefits before initiating TAVNEOS in patients with chronic infection, at increased risk of infection or who have been to places where certain infections are common. Adverse Reactions: The most common adverse reactions (≥5% of patients and higher in the TAVNEOS group vs. prednisone group) were: nausea, headache, hypertension, diarrhea, vomiting, rash, fatigue, upper abdominal pain, dizziness, blood creatinine increased, and paresthesia. Drug Interactions: Avoid coadministration of TAVNEOS with strong and moderate CYP3A4 enzyme inducers. Reduce TAVNEOS dose when co-administered with strong CYP3A4 enzyme inhibitors to 30 mg once daily. Monitor for adverse reactions and consider dose reduction of certain sensitive CYP3A4 substrates. Please see full TAVNEOS Prescribing Information . About Amgen Amgen is committed to unlocking the potential of biology for patients suffering from serious illnesses by discovering, developing, manufacturing and delivering innovative human therapeutics. This approach begins by using tools like advanced human genetics to unravel the complexities of disease and understand the fundamentals of human biology. Amgen focuses on areas of high unmet medical need and leverages its expertise to strive for solutions that improve health outcomes and dramatically improve people's lives. A biotechnology pioneer since 1980, Amgen has grown to be one of the world's leading independent biotechnology companies, has reached millions of patients around the world and is developing a pipeline of medicines with breakaway potential. Amgen is one of the 30 companies that comprise the Dow Jones Industrial Average and is also part of the Nasdaq-100 index. In 2022, Amgen was named one of the "World's Best Employers" by Forbes and one of "America's 100 Most Sustainable Companies" by Barron's. For more information, visit Amgen.com and follow us on Twitter, LinkedIn, Instagram, TikTok and YouTube. Amgen Forward-Looking Statements This news release contains forward-looking statements that are based on the current expectations and beliefs of Amgen. 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BioVie Provides Updates on Other Clinical Programs Vast majority of patients saw significant improvements in the Global Rating of Change (overall impression of patient’s daily abilities) with NE3107 treatment (p<0.0001 to p<0.05). NE3107 is associated with significant improvements in cognition as evidenced by the ADAS-Cog12 scale. 82% of 17 patients with MMSE >=20 experienced a 2.6 point decrease in ADAS-Cog12 (p=0.0046). Reductions in TNFa (considered to be an initial factor driving inflammation) after NE3107 treatment are significantly correlated with improvement in cognition. NE3107 treatment associated with trending improvements in ratio of p-tau:Ab. 60% of 10 patients with MMSE >=20 improved 0.002 in the ratio of p-tau / Ab (p=0.055). Early analyses of imaging data suggest fundamental biological improvements in blood flow and reduced oxidative stress that are consistent with the mechanism for NE3107 and are unlikely to be accounted for by placebo effect. No drug-related adverse events (AEs) were reported. Detailed results will be presented at the CTAD 2022 Annual Conference. CARSON CITY, Nev., Sept. 07, 2022 (GLOBE NEWSWIRE) -- BioVie Inc., (NASDAQ: BIVI) (“BioVie” or the “Company”) a clinical-stage company developing innovative drug therapies for the treatment of advanced liver disease and neurological and neurodegenerative disorders, today announced topline results from an investigator-Sponsored Phase 2 clinical trial of NE3107 for the treatment of Alzheimer’s Disease (AD). Updates from other trials underway are also provided. AD research has largely focused on Amyloid Beta (Ab) and phospho-tau (p-tau) for decades and has resulted in a large number of trials targeting these mechanisms.1 More recently, however, research focus has shifted towards targeting neuroinflammation, as evidenced by the 23 disease-modifying agents listed in clinicaltrials.gov in 2021 investigating inflammation or the immune system. NE3107 is the only molecule in this group that is pursuing a two-pronged approach targeting both neuroinflammation and insulin resistance. Furthermore, NE3107 is the only molecule in the group that is conducting a potentially pivotal Phase 3 trial (NCT04669028) that is currently underway in mild- to moderate-AD patients with co-primary endpoints of cognition, as measured by the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog12), and function, as measured by Alzheimer’s Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC), whereas 17 other agents are in Phase 2. This Phase 3 trial is expected to provide topline results in mid-2023. Tumor Necrosis Factor Alpha (TNFa) is a cytokine identified as a major regulator of inflammation given that its excessive activation is associated with chronic inflammation.2 It is considered to be the central mediator of inflammation due to its role at the top of the biochemical pathway that leads to the production of other inflammatory factors such as various cytokines (e.g., IFNg, IL-1b, IL23, IL-4, IL-17), neurotoxic Aβ peptide oligomers, activation of IKK and JNK (that leads to insulin resistance), and others. A large retrospective study analyzing the electronic medical records of 56 million unique patients demonstrated the linkage between TNFa and AD by showing that patients with rheumatoid arthritis and psoriasis taking TNF blocking agents had significantly lower AD risk.3 Preclinical studies showed NE3107 is a modulator of TNFa production through its ability to modulate the activation of the Extracellular Regulated Kinase (ERK) and Nuclear Factor kappa B (NFkB).4 By down regulating the activation of ERK and NFkB, NE3107 has been shown to reduce the production of TNFa.5 The Company’s newly generated data supporting a new patent application show that NE3107 inhibits inflammatory ERK activation and blocks the phosphorylation of TNF receptor 1 (TNFR1) in an IKK-MAP3K8-MEK dependent pathway to decrease forward-feeding TNF inflammatory cascades, thereby lowering the expression of other downstream inflammatory factors. Since the NE3107 Phase 3 trial underway is focused on cognition and function and is not focused on collecting neuroinflammatory biomarkers, the Company supported a Phase 2 investigator-initiated trial (NCT05227820) to explore the link between NE3107’s role in neuroinflammation and insulin resistance to the biomarkers historically used by the AD research community. It also was designed to provide, if possible, a glimpse into what can be expected regarding cognition and function when the Phase 3 trial reads out next year. This was done by using a modified ADAS-Cog12 scale for cognition and the Global Rating of Change (GRoC), which is an instrument that can be administered more easily in general clinical practices than the ADCS-CGIC. The Phase 2 trial— A Phase II Open-Label Study for the Use of Anti-Inflammatory, Insulin-Sensitizing NE3107 for Treatment of Cognitive Decline Due to Degenerative Dementias (NCT05227820) — is an exploratory biomarker study conducted by Dr. Sheldon Jordan6, who served as principal investigator for the trial. The trial was intended to explore NE3107’s potential role in real-world clinical practice as an exploratory precursor informing the design of subsequent placebo-controlled blinded studies. Results from Phase 2 Exploratory Biomarker Trial The trial enrolled a total of 23 patients – 17 patients with Mini-Mental State Examination (MMSE) scores greater than or equal to 20 (i.e., mild cognitive impairment [MCI] to mild AD) and 6 patients with MMSE <20 (i.e., moderate AD) – in an open-label, single arm study. The trial measured changes in cognition through verbal and visual test procedures, changes in biomarkers of Alzheimer’s disease and inflammation that can be measured in cerebral spinal fluid (CSF) and serum samples, and with functional magnetic resonance imaging techniques in patients before and after treatment with 20 mg of NE3107 twice daily for 3 months. Initial results showed that the measurements for most patients improved with NE3107 treatment, although MCI/mild AD patients showed greater change. The Global Rating of Change is a frequently used outcome measure that tracks improvements in a patient’s conditions, abilities and overall sense of well-being as perceived by the clinician, the caretakers and the patients. A large proportion of MCI/mild AD patients in the trial showed improvements as evidenced by an increase of the GRoC scale after treatment with NE3107 compared to baseline as scored by the clinician (94% of 17 patients improved, p=0.0001), the study partner (65% of 17 patients improved, p=0.078), and the patient (88% of 17 patients improved, p=0.0039). A similar pattern of improvements was observed within the total pool of patients. Several tools were used to assess changes in cognition, including a modified ADAS-Cog12, the Quick Dementia Rating Scale (QDRS), Mini-Mental State Examination (MMSE), and the Montreal Cognitive Assessment (MoCA). 82% of 17 MCI/mild AD patients improved with a mean ADAS-Cog12 change of -2.6 points (p=0.046) equating to a mean percentage change of -25.1% (p=0.0026). 61% of all 23 patients improved with a mean change of -1.04 (p=ns). A similar pattern of improvement was observed using the QDRS. 71% of 17 MCI/mild AD patients improved with a mean change of –1.35 (p=.0051). Improvements in ADAS-Cog12 were correlated with improvements in the Global Rating of Change as reported by the clinician (R=0.52, p<0.05) and the caretaker (R=0.46, p<.05). 62% of 13 MCI/mild AD patients had decreased plasma TNF with a mean change of -0.55 pg/mL (p=0.22). Importantly, improvements in TNFa statistically correlated to improvements in ADAS-Cog12 (R=0.70, p=0.0077). The ratio of p-tau to Ab42 has been shown by the Mayo Clinic and others to be an effective predictor of PET Ab status.7 63% of 16 patients improved with a mean change in the ratio of -0.0033 (p=0.069). While quantitative scoring of imaging data is currently underway, review of imaging scans and data by the study’s Principal Investigator (who is an imaging expert) indicates that NE3107 treatment in patients with MMSE >=20 is associated with certain changes in the brain. Among patients with MMSE >=20: 24% had increased blood flow in the brain while 6% declined. Blood flow is a marker for metabolism and brain activity. 41% to 47% had reduced the hyperactivation associated with cognitive impairment that results when the hippocampus (part of the brain that plays a major role in learning and memory) is stressed while 6% declined. This is a marker for network connectivity in the brain 41% had increased levels of glutathione (considered the master antioxidant and regulator of oxidative stress8) in the brain while 35% declined. No treatment related AEs were reported. The Company will present the final data and statistical analyses, which may deviate from the initial result presented here, at the Clinical Trial in Alzheimer’s Disease (CTAD) annual conference, to be held in San Francisco, CA November 29-December 2, 2022. Platform presentations and posters will provide detailed findings on changes on biomarker, neuropsychological assessments, and advanced MRI imaging. Research papers are being prepared to present the findings and will be submitted to peer-reviewed journals for publication. “Through our work, we are seeking to deepen our understanding of brain degeneration and ultimately identify promising treatments that have the potential to counteract the degenerative process. Results from this trial provide encouraging signals that NE3107 may offer significant potential to reduce neuroinflammation and potentially improve metabolic parameters such as glutathione in the brain, and warrant further study in this patient population,” said Dr. Jordan. “I was surprised to see imaging data changes and how so many patients had increased GRoC score, indicating they can perform more activities of daily living." “We are delighted to support the work of Dr. Jordan and his team and are very pleased to have this initial data-driven validation of NE3107’s potential role for the treatment of people suffering from cognitive impairment and dementia,” stated Dr. Joseph Palumbo, BioVie’s Chief Medical Officer. “Despite this being an open label study, the insights provided are instructional and directionally very interesting. While it is not possible to isolate the placebo effect in an open label study as a placebo-controlled double blinded trial can, results on TPO arterial spin label imaging, hippocampal blood oxygen level-dependent imaging, brain NMR spectroscopy measuring glutathione, and peripheral TNF reduction from this study provide helpful information to plan our next steps.” “This study provides us with an early opportunity to assess the effects of NE3107’s mechanism of action in the brain, and these topline results represent the first detailed data linking NE3107’s role in neuroinflammation and insulin resistance with the traditional biomarkers of interest to the AD research community,” added Cuong V. Do, President and CEO of BioVie. “I was excited about correlation of TNFa reduction with improvements in cognition and how treated patients saw an improvement in the ratio of p-tau:Ab. We supported Dr. Jordan’s Investigator-Sponsored trial as an exploratory biomarker study to guide our efforts to design future placebo-controlled trials to examine the potential impact of NE3107 on traditional AD biomarkers and measures of cognition and function. We are very grateful for the work of Dr. Jordan and his team on this important study and look forward to the team’s presentation at CTAD later this year.” Commenting on the mixed results observed in AD research over the decades, Mr. Do added, “AD drug development at BioVie is based on the evidence that AD pathology is multifactorial in nature. While Ab and p-tau are important factors, decades of research on dozens of agents have not conclusively correlated improvements on these individual factors to improvements in cognition. We believe additional factors such as inflammation, insulin resistance, metabolic dyshomeostasis, apoptosis, oxidative stress, and glucose utilization also play critical roles in AD etiology. Data shows that NE3107’s ability to reduce TNFa (the major regulator of inflammation) is highly correlated to improvements in cognition. We are pleased that the Principal Investigator observed these changes in 23 patients in only 3 months. We hypothesize that the modulation of TNFa levels and its inflammatory activation via TNFR1 lead to a multitude of changes among the many factors downstream from this master regulator, which collectively lead to improvements in neuronal health and cognition.” Update on other clinal trials In addition to the Phase 2 exploratory biomarker trial, the Company has three other trials underway. The potentially pivotal Phase 3 trial for NE3107 in AD (NCT04669028) has enrolled one-half of the targeted 316 patients. In blinded data, no drug-related adverse events have been seen in daily medical reviews. The study pre-specified the potential to increase enrollment up to 400 patients as deemed appropriate through a review by the data safety monitoring board (DSMB) in a manner that is blinded to the Company. This DSMB review will take place later this year and will determine if a sample size adjustment is needed for the purpose of enhancing the probability of achieving statistical significance. If no sample size adjustments are needed, the Company expects full enrollment of the study by the end of the year, enabling topline data readout by mid-2023. The study may be delayed if additional patients need to be enrolled in the event of a DSMB recommendation. The Phase 2 trial (NCT05083260) is enrolling 40 patients to examine NE3107 in Parkinson’s disease (PD) with two design objectives. The primary objective is a drug-drug interaction study as requested by the FDA to demonstrate the absence of adverse interactions of NE3107 with levodopa in humans (no indications of adverse DDI were observed in prior animal studies). The secondary objective is to explore an efficacy signal and determine if preclinical indications of promotoric activity and apparent enhancement of levodopa activity in MPTP rodents and marmosets can be observed in humans. In preclinical studies, NE3107 had promotoric activity equal to levodopa and the combination of NE3107 with levodopa was superior to either agent alone, providing the most “on time” without dyskinesia. The Company expects the trial to be fully enrolled in the next couple of months and data readout by the end of 2022. Similar to the AD Phase 3, no drug-related adverse events have been seen in daily medical reviews. We are detecting an efficacy signal among patients who have completed 28 days of treatment, but more data is needed to quantify the full therapeutic impact. The Phase 2b trial for BIV201 in refractory ascites (NCT04112199) is enrolling 30 patients with co-primary endpoints measuring the incidence of ascites-related complications over 180 days and change in ascites fluid removed over 90 days. The trial is taking much longer than expected. Patient recruitment has been hampered by Covid-19, which appears to have disproportionately affected this population of very sick patients. The pace of patient screening, however, appears to be picking up in recent weeks. At this pace, the Company anticipates data readout by mid-2023. The updated corporate overview and additional information can be found at . About BioVie BioVie Inc. (NASDAQ: BIVI) is a clinical-stage company developing innovative therapies to overcome unmet medical needs in chronic debilitating conditions. In neurodegenerative disease, the Company’s drug candidate NE3107 inhibits inflammatory activation of ERK and NFkB (e.g., TNF signaling) that leads to neuroinflammation and insulin resistance, but not their homeostatic functions (e.g., insulin signaling and neuron growth and survival). Both are drivers of Alzheimer’s and Parkinson’s diseases. The Company is conducting a potentially pivotal Phase 3 randomized, double blind, placebo controlled, parallel group, multicenter study to evaluate NE3107 in patients who have mild to moderate Alzheimer's disease (NCT04669028) and is targeting primary completion in mid-2023. An estimated six million Americans suffer from Alzheimer’s. A Phase 2 study of NE3107 in Parkinson’s disease (NCT05083260) is enrolling patients and expects to have topline data readout by the end of 2022. In liver disease, the Company’s Orphan drug candidate BIV201 (continuous infusion terlipressin), with FDA Fast Track status, is being evaluated in a US Phase 2b study for the treatment of refractory ascites due to liver cirrhosis with top-line results anticipated in mid-2023. BIV201 is administered as a patent-pending liquid formulation. The active agent is approved in about 40 countries for related complications of advanced liver cirrhosis but is not available in the US or Japan. For more information, visit Forward-Looking Statements This press release contains forward-looking statements, which may be identified by words such as "expect," "look forward to," "anticipate" "intend," "plan," "believe," "seek," "estimate," "will," "project" or words of similar meaning. Although BioVie Inc. believes such forward-looking statements are based on reasonable assumptions, it can give no assurance that its expectations will be attained. Actual results may vary materially from those expressed or implied by the statements herein due to the Company's ability to successfully raise sufficient capital on reasonable terms or at all, available cash on hand and contractual and statutory limitations that could impair our ability to pay future dividends, our ability to complete our pre-clinical or clinical studies and to obtain approval for our product candidates, to successfully defend potential future litigation, changes in local or national economic conditions as well as various additional risks, many of which are now unknown and generally out of the Company's control, and which are detailed from time to time in reports filed by the Company with the SEC, including quarterly reports on Form 10-Q, reports on Form 8-K and annual reports on Form 10-K. BioVie Inc. does not undertake any duty to update any statements contained herein (including any forward-looking statements), except as required by law. Abbreviations Used Ab Amyloid beta AD Alzheimer’s disease ADAS Cog 12 Alzheimer's Disease Assessment Scale-Cognitive subscale 12 ADCS-CGIC Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change Scale AKI Acute kidney injury CSF Cerebral spinal fluid CTAD Clinical Trials on Alzheimer’s Disease (a medical conference) DSMB Data and Safety Monitoring Board ERK Extracellular signal regulated kinase 1 and 2 GRoC Global Rating of Change HRS Hepatic renal syndrome IKK IkappaB kinase, an inflammatory signaling protein that activates NFkB INFg Interferon gamma IL-1b Interleukin one beta IL- 4, 17, 23 Interleukin 4, 17, 23 JNK c-Jun N-terminal kinases, an inflammatory signaling protein kinase MAP3K8 Mitogen-activated protein kinase kinase kinase 8, an inflammatory signaling protein involved in pathological inflammation MCI Mild cognitive impairment MEK Mitogen and ERK kinase, an ERK activating protein kinase MMSE Mini Mental State Examination MoCA Montreal Cognitive Assessment NE3107 17a-ethynyl-androst-5-ene-3b,7b,17b-triol NFkB Nuclear factor kappa-light-chain-enhancer of activated B cells p38 One of several mitogen-activated protein kinases involved in inflammatory signaling PD Parkinson’s disease pg picogram p-tau Hyperphosphorylated tau protein QDRS Quick Dementia Rating Scale TNFa Tumor necrosis factor alpha TNFR1 Tumor necrosis factor receptor R1 For Investor Relations Inquiries: Contact: Bruce Mackle Managing Director LifeSci Advisors, LLC bmackle@lifesciadvisors.com 1 Cummings et al. 2022 DOI: 10.1002/trc2.12295 2 Jang et al. Int J Mol Sci. 2021 Mar; 22(5): 2719. 3 Zhou et al. 2020 PLoS ONE 15(3): e0229819. 4 Lu 2010 Am J Physiol Endocrinol Metab 298 E1036; Wang 2010 J Pharmacol Exp Ther 333 70 5 Offner 2009 J Pharmacol Exp Ther 329 1100 6 Dr. Jordan is Adjunct Clinical Associate Professor of Neurology at UCLA. Dr. Jordan is board certified by the American Board of Psychiatry & Neurology, American Board of Clinical Neurophysiology, American Board of Addiction Medicine, and American Board of Interventional Pain Medicine. He was elected as Fellow of the American Academy of Neurology and holds additional certifications from the American Society of Neuroimaging in Magnetic Resonance Imaging, Computed Tomography and Ultrasonography. Dr. Jordan is the senior author of a recent paper on quantitative MRI imaging in dementia (Kuhn et al., 2021 Quant Imaging Med Surg 11) 7 Campbell et al. Alzheimers Dement (Amst). 2021; 13(1): e12190. 8 Teskey et al. Advances in Clinical Chemistry Volume 87, 2018, Pages 141-159