Leukoencephalopathy, Progressive Multifocal

MINT Study Results Show Clinically Meaningful and Statistically Significant Efficacy in AChR+ and MuSK+ Patients First and Only Phase 3 Placebo-Controlled gMG Trial for a Biologic That Tapered Corticosteroid Use THOUSAND OAKS, Calif., Oct. 15, 2024 /PRNewswire/ -- Amgen (NASDAQ:AMGN) today announced the presentation of positive top-line results from the Phase 3 MINT trial evaluating the efficacy and safety of UPLIZNA® (inebilizumab-cdon) for the treatment of adults with generalized myasthenia gravis (gMG), a rare autoimmune disorder. Results from this randomized, double-blind, placebo-controlled, parallel-group trial will be presented at the Myasthenia Gravis Foundation of America (MGFA) Scientific Session during the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) Annual Meeting, taking place Oct. 15-18 in Savannah, Georgia. The trial met its primary endpoint, with a statistically significant change from baseline in Myasthenia Gravis Activities of Daily Living (MG-ADL) score for UPLIZNA (-4.2) compared with placebo (-2.2) (difference: –1.9, p<0.0001) at Week 26 for the combined study population. The study included patients who are acetylcholine receptor autoantibody-positive (AChR+) and those who are muscle-specific kinase autoantibody-positive (MuSK+), with participants receiving UPLIZNA or placebo on Day 1 and Day 15. UPLIZNA demonstrated continued improvement through Week 26. Notably, patients who entered the study taking corticosteroids were tapered down starting at Week 4 to prednisone 5 mg per day by Week 24. No new safety signals were identified. "Patients living with generalized myasthenia gravis deserve an effective treatment option that provides long-term symptom relief. Once approved, UPLIZNA is expected to offer a new option for patients earlier in their treatment plan," said Jay Bradner, M.D., executive vice president, Research and Development, and chief scientific officer at Amgen. "UPLIZNA targets CD19+ pre-B cells, mature B-cells and some plasmablasts, which are drivers of the disease. The clinically significant results from the MINT trial further strengthen the growing evidence for UPLIZNA in severe autoimmune diseases and reinforce Amgen's leadership in B-cell targeting therapeutics." Key secondary endpoints were tested sequentially in a predefined order. UPLIZNA demonstrated a statistically significant and clinically meaningful change from baseline compared to placebo for the first four key secondary endpoints. UPLIZNA demonstrated a statistically significant change in Quantitative Myasthenia Gravis (QMG) score for the combined population (-4.8) compared to placebo (-2.3) at Week 26 (difference: -2.5, p=0.0002). In the AChR+ population, UPLIZNA demonstrated mean change from baseline (-4.2) in MG-ADL score at Week 26 compared to placebo (-2.4) (difference: -1.8, p=0.0015). In the AChR+ population, UPLIZNA demonstrated mean change from baseline (-4.4) in QMG score at Week 26 compared to placebo (-2.0) (difference -2.5, p=0.0011). In the MuSK+ population, UPLIZNA demonstrated mean change from baseline (-3.9) in MG-ADL score at Week 26 compared to placebo (-1.7) (difference -2.2, p=0.0297). Additionally, in the MuSK+ population, the mean change from baseline in QMG score at Week 26 showed a trend favoring UPLIZNA but was not statistically significant (-5.2 for UPLIZNA and -3.0 for placebo, difference -2.3, p=0.1326). "Myasthenia gravis can have a profound impact on patients by causing severe fatigable muscle weakness that impairs physical functioning, activities of daily living and quality of life," said Richard J. Nowak, M.D., M.S., global principal study investigator and director of the Myasthenia Gravis Clinic at Yale University. "This trial demonstrates clinically meaningful benefits of UPLIZNA, a twice-yearly infused medicine with a unique mechanism of action that selectively targets and depletes CD19+ B cells, which are key upstream drivers of myasthenia gravis. MINT is also the only Phase 3 biologic trial that included a protocol-specified steroid taper, an important consideration for patients as effects of prolonged high-dose steroid use contribute to the overall burden of disease." The overall safety results during the placebo-controlled period of the trial were consistent with the known safety profile of UPLIZNA. The most common treatment-emergent adverse events were COVID-19, nasopharyngitis, urinary tract infection, infusion related reaction, headache and cough in the combined population. MINT is the largest placebo-controlled gMG clinical trial for a biologic therapy (238 adults) and enrolled the largest number of patients (48 adults) who are MuSK+. The trial also included 190 adults who are AChR+. Further data will characterize placebo-controlled efficacy and safety of UPLIZNA over 12 months in AChR+ patients with gMG. At the 2024 AANEM Annual Meeting, Amgen will also be presenting a poster titled, "The Burden of Glucocorticoid Use Among Patients with Generalized Myasthenia Gravis in the United States," highlighting how higher use of glucocorticoids was associated with more toxicities and overall health care resource utilization and costs. UPLIZNA is currently approved for the treatment of neuromyelitis optica spectrum disorder (NMOSD) in adult patients who are anti-aquaporin-4 (AQP4) antibody positive in the United States, European Union, Brazil and Canada, among other countries. UPLIZNA was also recently granted Breakthrough Therapy Designation for IgG4-Related Diseases by FDA following Phase 3 results announced in June. Based on the MINT primary results, Amgen is planning to file for approval in the U.S., followed by other key markets. About the MINT Trial The MINT trial is a randomized, double-blind, placebo-controlled, parallel-group trial (NCT04524273) evaluating the efficacy and safety of UPLIZNA in adults with gMG. The trial enrolled 238 adults with gMG, including 190 patients who are acetylcholine receptor autoantibody-positive (AChR+) and 48 patients who are muscle-specific kinase autoantibody-positive (MuSK+). Eligibility criteria at screening and randomization included a Myasthenia Gravis Foundation of America (MGFA) classification of II, III, or IV disease, MG-ADL score between 6 and 10 with greater than 50% of this score attributed to non-ocular items, or an MG-ADL score of at least 11, QMG score of at least 11, and use of a corticosteroid and/or non-steroidal immunosuppressant. The primary endpoint was change from baseline in MG-ADL score at Week 26 in the combined population. Key secondary endpoints included change from baseline in QMG scores in the combined study population; change from baseline in MG-ADL score at Week 26 for the AChR+ cohort and separately the MuSK+ cohort; and change from baseline in QMG score at Week 26 for the AChR+ cohort and separately the MuSK+ cohort. Patients who entered the study taking a corticosteroid were tapered down to prednisone 5 mg a day, starting at Week 4 to Week 24. The MINT trial also includes an optional three-year open-label treatment period. About Generalized Myasthenia Gravis (gMG) Generalized myasthenia gravis (gMG) is a rare, chronic, B-cell-mediated autoimmune disorder that impairs neuromuscular communication and can cause muscle weakness, trouble breathing, difficulty swallowing and impaired speech and vision.1-4 Approximately 85% of patients with myasthenia gravis have the generalized form, or gMG.4,5 The prevalence and incidence of gMG are increasing worldwide.5 There are between 80,000 and 100,000 patients with myasthenia gravis in the U.S.6,7 Approximately 85% of patients with myasthenia gravis have detectable antibodies against AChR, and approximately 7% have detectable antibodies against MuSK.8 Global prevalence is estimated at 2-36 cases per 100,000.9 The disease is more frequently seen in young women (age 20-30) and men aged 50 years and older.5,9 B cells are central to the pathogenesis of gMG. The disease is thought to be primarily driven by pathogenic CD19+ plasmablasts and plasma cells that target critical proteins in the neuromuscular junction.1-3 About UPLIZNA® (inebilizumab-cdon) in NMOSD INDICATION UPLIZNA® (inebilizumab-cdon) is indicated for the treatment of neuromyelitis optica spectrum disorder (NMOSD) in adult patients who are anti-aquaporin-4 (AQP4) antibody positive. IMPORTANT SAFETY INFORMATION UPLIZNA is contraindicated in patients with: A history of life-threatening infusion reaction to UPLIZNA Active hepatitis B infection Active or untreated latent tuberculosis WARNINGS AND PRECAUTIONS Infusion Reactions: UPLIZNA can cause infusion reactions, which can include headache, nausea, somnolence, dyspnea, fever, myalgia, rash, or other symptoms. Infusion reactions were most common with the first infusion but were also observed during subsequent infusions. Administer pre-medication with a corticosteroid, an antihistamine, and an anti-pyretic. Infections: The most common infections reported by UPLIZNA-treated patients in the randomized and open-label periods included urinary tract infection (20%), nasopharyngitis (13%), upper respiratory tract infection (8%), and influenza (7%). Delay UPLIZNA administration in patients with an active infection until the infection is resolved. Increased immunosuppressive effects are possible if combining UPLIZNA with another immunosuppressive therapy. The risk of Hepatitis B Virus (HBV) reactivation has been observed with other B-cell-depleting antibodies. Perform HBV screening in all patients before initiation of treatment with UPLIZNA. Do not administer to patients with active hepatitis. Although no confirmed cases of Progressive Multifocal Leukoencephalopathy (PML) were identified in UPLIZNA clinical trials, JC virus infection resulting in PML has been observed in patients treated with other B-cell-depleting antibodies and other therapies that affect immune competence. At the first sign or symptom suggestive of PML, withhold UPLIZNA and perform an appropriate diagnostic evaluation. Patients should be evaluated for tuberculosis risk factors and tested for latent infection prior to initiating UPLIZNA. Vaccination with live-attenuated or live vaccines is not recommended during treatment and after discontinuation, until B-cell repletion. Reduction in Immunoglobulins: There may be a progressive and prolonged hypogammaglobulinemia or decline in the levels of total and individual immunoglobulins such as immunoglobulins G and M (IgG and IgM) with continued UPLIZNA treatment. Monitor the level of immunoglobulins at the beginning, during, and after discontinuation of treatment with UPLIZNA until B-cell repletion especially in patients with opportunistic or recurrent infections. Fetal Risk: May cause fetal harm based on animal data. Advise females of reproductive potential of the potential risk to a fetus and to use an effective method of contraception during treatment and for 6 months after stopping UPLIZNA. Adverse Reactions: The most common adverse reactions (at least 10% of patients treated with UPLIZNA and greater than placebo) were urinary tract infection and arthralgia. For additional information on UPLIZNA, please see the Full Prescribing Information at . About Amgen Amgen discovers, develops, manufactures, and delivers innovative medicines to help millions of patients in their fight against some of the world's toughest diseases. More than 40 years ago, Amgen helped to establish the biotechnology industry and remains on the cutting-edge of innovation, using technology and human genetic data to push beyond what's known today. Amgen is advancing a broad and deep pipeline that builds on its existing portfolio of medicines to treat cancer, heart disease, osteoporosis, inflammatory diseases and rare diseases. In 2024, Amgen was named one of the "World's Most Innovative Companies" by Fast Company and one of "America's Best Large Employers" by Forbes, among other external recognitions. Amgen is one of the 30 companies that comprise the Dow Jones Industrial Average®, and it is also part of the Nasdaq-100 Index®, which includes the largest and most innovative non-financial companies listed on the Nasdaq Stock Market based on market capitalization. For more information, visit Amgen.com and follow Amgen on X, LinkedIn, Instagram, TikTok, YouTube and Threads. Forward-Looking Statements This news release contains forward-looking statements that are based on the current expectations and beliefs of Amgen. All statements, other than statements of historical fact, are statements that could be deemed forward-looking statements, including any statements on the outcome, benefits and synergies of collaborations, or potential collaborations, with any other company (including BeiGene, Ltd. or Kyowa Kirin Co., Ltd.), the performance of Otezla® (apremilast) (including anticipated Otezla sales growth and the timing of non-GAAP EPS accretion), our acquisitions of Teneobio, Inc., ChemoCentryx, Inc., or Horizon Therapeutics plc (including the prospective performance and outlook of Horizon's business, performance and opportunities, any potential strategic benefits, synergies or opportunities expected as a result of such acquisition, and any projected impacts from the Horizon acquisition on our acquisition-related expenses going forward), as well as estimates of revenues, operating margins, capital expenditures, cash, other financial metrics, expected legal, arbitration, political, regulatory or clinical results or practices, customer and prescriber patterns or practices, reimbursement activities and outcomes, effects of pandemics or other widespread health problems on our business, outcomes, progress, and other such estimates and results. Forward-looking statements involve significant risks and uncertainties, including those discussed below and more fully described in the Securities and Exchange Commission reports filed by Amgen, including our most recent annual report on Form 10-K and any subsequent periodic reports on Form 10-Q and current reports on Form 8-K. Unless otherwise noted, Amgen is providing this information as of the date of this news release and does not undertake any obligation to update any forward-looking statements contained in this document as a result of new information, future events or otherwise. No forward-looking statement can be guaranteed and actual results may differ materially from those we project. Discovery or identification of new product candidates or development of new indications for existing products cannot be guaranteed and movement from concept to product is uncertain; consequently, there can be no guarantee that any particular product candidate or development of a new indication for an existing product will be successful and become a commercial product. Further, preclinical results do not guarantee safe and effective performance of product candidates in humans. The complexity of the human body cannot be perfectly, or sometimes, even adequately modeled by computer or cell culture systems or animal models. The length of time that it takes for us to complete clinical trials and obtain regulatory approval for product marketing has in the past varied and we expect similar variability in the future. Even when clinical trials are successful, regulatory authorities may question the sufficiency for approval of the trial endpoints we have selected. We develop product candidates internally and through licensing collaborations, partnerships and joint ventures. Product candidates that are derived from relationships may be subject to disputes between the parties or may prove to be not as effective or as safe as we may have believed at the time of entering into such relationship. Also, we or others could identify safety, side effects or manufacturing problems with our products, including our devices, after they are on the market. Our results may be affected by our ability to successfully market both new and existing products domestically and internationally, clinical and regulatory developments involving current and future products, sales growth of recently launched products, competition from other products including biosimilars, difficulties or delays in manufacturing our products and global economic conditions. 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Further, while we routinely obtain patents for our products and technology, the protection offered by our patents and patent applications may be challenged, invalidated or circumvented by our competitors, or we may fail to prevail in present and future intellectual property litigation. We perform a substantial amount of our commercial manufacturing activities at a few key facilities, including in Puerto Rico, and also depend on third parties for a portion of our manufacturing activities, and limits on supply may constrain sales of certain of our current products and product candidate development. An outbreak of disease or similar public health threat, such as COVID-19, and the public and governmental effort to mitigate against the spread of such disease, could have a significant adverse effect on the supply of materials for our manufacturing activities, the distribution of our products, the commercialization of our product candidates, and our clinical trial operations, and any such events may have a material adverse effect on our product development, product sales, business and results of operations. We rely on collaborations with third parties for the development of some of our product candidates and for the commercialization and sales of some of our commercial products. In addition, we compete with other companies with respect to many of our marketed products as well as for the discovery and development of new products. Further, some raw materials, medical devices and component parts for our products are supplied by sole third-party suppliers. Certain of our distributors, customers and payers have substantial purchasing leverage in their dealings with us. The discovery of significant problems with a product similar to one of our products that implicate an entire class of products could have a material adverse effect on sales of the affected products and on our business and results of operations. Our efforts to collaborate with or acquire other companies, products or technology, and to integrate the operations of companies or to support the products or technology we have acquired, may not be successful. There can be no guarantee that we will be able to realize any of the strategic benefits, synergies or opportunities arising from the Horizon acquisition, and such benefits, synergies or opportunities may take longer to realize than expected. We may not be able to successfully integrate Horizon, and such integration may take longer, be more difficult or cost more than expected. A breakdown, cyberattack or information security breach of our information technology systems could compromise the confidentiality, integrity and availability of our systems and our data. Our stock price is volatile and may be affected by a number of events. Our business and operations may be negatively affected by the failure, or perceived failure, of achieving our environmental, social and governance objectives. The effects of global climate change and related natural disasters could negatively affect our business and operations. Global economic conditions may magnify certain risks that affect our business. Our business performance could affect or limit the ability of our Board of Directors to declare a dividend or our ability to pay a dividend or repurchase our common stock. We may not be able to access the capital and credit markets on terms that are favorable to us, or at all. Any scientific information discussed in this news release relating to new indications for our products is preliminary and investigative and is not part of the labeling approved by the U.S. Food and Drug Administration for the products. The products are not approved for the investigational use(s) discussed in this news release, and no conclusions can or should be drawn regarding the safety or effectiveness of the products for these uses. CONTACT: Amgen, Thousand Oaks Madison Howard, 773-636-4910 (media) Elissa Snook, 609-251-1407 (media) Justin Claeys, 805-313-9775 (investors) References Yi, J. S., Guptill, J. T., Stathopoulos, P., Nowak, R. J., & O'Connor, K. C. (2018). B cells in the pathophysiology of myasthenia gravis. Muscle Nerve, 57(2):172-184. Willcox H. N., Newsom-Davis, J., & Calder, L. R. (1984). Cell types required for anti-acetylcholine receptor antibody synthesis by cultured thymocytes and blood lymphocytes in myasthenia gravis. Clinical and Experimental Immunology., 58:97-106. Stathopoulos P., Kumar, A., Nowak, R. J., & O'Connor, K. C. (2017). Autoantibody-producing plasmablasts after B cell depletion identified in muscle-specific kinase myasthenia gravis. JCI Insight, 2(17):e94263. Lazaridis K., & Tzartos, S. J. (2020). Autoantibody Specificities in Myasthenia Gravis; Implications for Improved Diagnostics and Therapeutics. Frontiers in Immunology, 11:212. Dresser L., Wlodarski, R., Rezania, K., & Soliven, B. (2021). Myasthenia Gravis: Epidemiology, Pathophysiology and Clinical Manifestations. J Clin Med, 10(11):2235. Ye et al. Frontiers in Neurology. (2024);15:1339167. Rodrigues E., Umeh, E., Aishwarya, Navaratnarajah, N., Cole, A., & Moy, K. (2024). Incidence and prevalence of myasthenia gravis in the United States: A claims-based analysis. Muscle Nerve, 69(2):166-171. Hehir, M. K., & Silvestri, N. J. (2018). Generalized myasthenia gravis: classification, clinical presentation, natural history, and epidemiology. Neurologic Clinics, 36:253-60. Bubuioc, A. M., Kudebayeva, A., Turuspekova, S., Lisnic, V., & Leone, M. A. (2021). The epidemiology of myasthenia gravis. Journal of Medicine and Life, 14(1):7-16. SOURCE Amgen WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

MINT Study Results Show Clinically Meaningful and Statistically Significant Efficacy in AChR+ and MuSK+ Patients First and Only Phase 3 Placebo-Controlled gMG Trial for a Biologic That Tapered Corticosteroid Use THOUSAND OAKS, Calif. , Oct. 15, 2024 /PRNewswire/ -- Amgen (NASDAQ:AMGN) today announced the presentation of positive top-line results from the Phase 3 MINT trial evaluating the efficacy and safety of UPLIZNA ® (inebilizumab-cdon) for the treatment of adults with generalized myasthenia gravis (gMG), a rare autoimmune disorder. Results from this randomized, double-blind, placebo-controlled, parallel-group trial will be presented at the Myasthenia Gravis Foundation of America (MGFA) Scientific Session during the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) Annual Meeting, taking place Oct. 15-18 in Savannah, Georgia . The trial met its primary endpoint, with a statistically significant change from baseline in Myasthenia Gravis Activities of Daily Living (MG-ADL) score for UPLIZNA (-4.2) compared with placebo (-2.2) (difference: –1.9, p<0.0001) at Week 26 for the combined study population. The study included patients who are acetylcholine receptor autoantibody-positive (AChR+) and those who are muscle-specific kinase autoantibody-positive (MuSK+), with participants receiving UPLIZNA or placebo on Day 1 and Day 15. UPLIZNA demonstrated continued improvement through Week 26. Notably, patients who entered the study taking corticosteroids were tapered down starting at Week 4 to prednisone 5 mg per day by Week 24. No new safety signals were identified. "Patients living with generalized myasthenia gravis deserve an effective treatment option that provides long-term symptom relief. Once approved, UPLIZNA is expected to offer a new option for patients earlier in their treatment plan," said Jay Bradner , M.D., executive vice president, Research and Development, and chief scientific officer at Amgen . "UPLIZNA targets CD19+ pre-B cells, mature B-cells and some plasmablasts, which are drivers of the disease. The clinically significant results from the MINT trial further strengthen the growing evidence for UPLIZNA in severe autoimmune diseases and reinforce Amgen 's leadership in B-cell targeting therapeutics." Key secondary endpoints were tested sequentially in a predefined order. UPLIZNA demonstrated a statistically significant and clinically meaningful change from baseline compared to placebo for the first four key secondary endpoints. Additionally, in the MuSK+ population, the mean change from baseline in QMG score at Week 26 showed a trend favoring UPLIZNA but was not statistically significant (-5.2 for UPLIZNA and -3.0 for placebo, difference -2.3, p=0.1326). "Myasthenia gravis can have a profound impact on patients by causing severe fatigable muscle weakness that impairs physical functioning, activities of daily living and quality of life," said Richard J. Nowak , M.D., M.S., global principal study investigator and director of the Myasthenia Gravis Clinic at Yale University . "This trial demonstrates clinically meaningful benefits of UPLIZNA, a twice-yearly infused medicine with a unique mechanism of action that selectively targets and depletes CD19+ B cells, which are key upstream drivers of myasthenia gravis. MINT is also the only Phase 3 biologic trial that included a protocol-specified steroid taper, an important consideration for patients as effects of prolonged high-dose steroid use contribute to the overall burden of disease." The overall safety results during the placebo-controlled period of the trial were consistent with the known safety profile of UPLIZNA. The most common treatment-emergent adverse events were COVID-19, nasopharyngitis, urinary tract infection, infusion related reaction, headache and cough in the combined population. MINT is the largest placebo-controlled gMG clinical trial for a biologic therapy (238 adults) and enrolled the largest number of patients (48 adults) who are MuSK+. The trial also included 190 adults who are AChR+. Further data will characterize placebo-controlled efficacy and safety of UPLIZNA over 12 months in AChR+ patients with gMG. At the 2024 AANEM Annual Meeting, Amgen will also be presenting a poster titled, "The Burden of Glucocorticoid Use Among Patients with Generalized Myasthenia Gravis in the United States ," highlighting how higher use of glucocorticoids was associated with more toxicities and overall health care resource utilization and costs. UPLIZNA is currently approved for the treatment of neuromyelitis optica spectrum disorder (NMOSD) in adult patients who are anti-aquaporin-4 (AQP4) antibody positive in the United States , European Union , Brazil and Canada , among other countries. UPLIZNA was also recently granted Breakthrough Therapy Designation for IgG4-Related Diseases by FDA following Phase 3 results announced in June. Based on the MINT primary results, Amgen is planning to file for approval in the U.S. , followed by other key markets. About the MINT Trial The MINT trial is a randomized, double-blind, placebo-controlled, parallel-group trial ( NCT04524273 ) evaluating the efficacy and safety of UPLIZNA in adults with gMG. The trial enrolled 238 adults with gMG, including 190 patients who are acetylcholine receptor autoantibody-positive (AChR+) and 48 patients who are muscle-specific kinase autoantibody-positive (MuSK+). Eligibility criteria at screening and randomization included a Myasthenia Gravis Foundation of America (MGFA) classification of II, III, or IV disease, MG-ADL score between 6 and 10 with greater than 50% of this score attributed to non-ocular items, or an MG-ADL score of at least 11, QMG score of at least 11, and use of a corticosteroid and/or non-steroidal immunosuppressant. The primary endpoint was change from baseline in MG-ADL score at Week 26 in the combined population. Key secondary endpoints included change from baseline in QMG scores in the combined study population; change from baseline in MG-ADL score at Week 26 for the AChR+ cohort and separately the MuSK+ cohort; and change from baseline in QMG score at Week 26 for the AChR+ cohort and separately the MuSK+ cohort. Patients who entered the study taking a corticosteroid were tapered down to prednisone 5 mg a day, starting at Week 4 to Week 24. The MINT trial also includes an optional three-year open-label treatment period. About Generalized Myasthenia Gravis (gMG) Generalized myasthenia gravis (gMG) is a rare, chronic, B-cell-mediated autoimmune disorder that impairs neuromuscular communication and can cause muscle weakness, trouble breathing, difficulty swallowing and impaired speech and vision. 1-4 Approximately 85% of patients with myasthenia gravis have the generalized form, or gMG. 4,5 The prevalence and incidence of gMG are increasing worldwide. 5 There are between 80,000 and 100,000 patients with myasthenia gravis in the U.S. 6,7 Approximately 85% of patients with myasthenia gravis have detectable antibodies against AChR, and approximately 7% have detectable antibodies against MuSK. 8 Global prevalence is estimated at 2-36 cases per 100,000. 9 The disease is more frequently seen in young women (age 20-30) and men aged 50 years and older. 5,9 B cells are central to the pathogenesis of gMG. The disease is thought to be primarily driven by pathogenic CD19+ plasmablasts and plasma cells that target critical proteins in the neuromuscular junction. 1-3 About UPLIZNA® (inebilizumab-cdon) in NMOSD INDICATION UPLIZNA® (inebilizumab-cdon) is indicated for the treatment of neuromyelitis optica spectrum disorder (NMOSD) in adult patients who are anti-aquaporin-4 (AQP4) antibody positive. IMPORTANT SAFETY INFORMATION UPLIZNA is contraindicated in patients with: WARNINGS AND PRECAUTIONS Infusion Reactions: UPLIZNA can cause infusion reactions, which can include headache, nausea, somnolence, dyspnea, fever, myalgia, rash, or other symptoms. Infusion reactions were most common with the first infusion but were also observed during subsequent infusions.  Administer pre-medication with a corticosteroid, an antihistamine, and an anti-pyretic. Infections: The most common infections reported by UPLIZNA-treated patients in the randomized and open-label periods included urinary tract infection (20%), nasopharyngitis (13%), upper respiratory tract infection (8%), and influenza (7%). Delay UPLIZNA administration in patients with an active infection until the infection is resolved. Increased immunosuppressive effects are possible if combining UPLIZNA with another immunosuppressive therapy. The risk of Hepatitis B Virus (HBV) reactivation has been observed with other B-cell-depleting antibodies. Perform HBV screening in all patients before initiation of treatment with UPLIZNA. Do not administer to patients with active hepatitis. Although no confirmed cases of Progressive Multifocal Leukoencephalopathy (PML) were identified in UPLIZNA clinical trials, JC virus infection resulting in PML has been observed in patients treated with other B-cell-depleting antibodies and other therapies that affect immune competence. At the first sign or symptom suggestive of PML, withhold UPLIZNA and perform an appropriate diagnostic evaluation. Patients should be evaluated for tuberculosis risk factors and tested for latent infection prior to initiating UPLIZNA. Vaccination with live-attenuated or live vaccines is not recommended during treatment and after discontinuation, until B-cell repletion. Reduction in Immunoglobulins: There may be a progressive and prolonged hypogammaglobulinemia or decline in the levels of total and individual immunoglobulins such as immunoglobulins G and M (IgG and IgM) with continued UPLIZNA treatment. Monitor the level of immunoglobulins at the beginning, during, and after discontinuation of treatment with UPLIZNA until B-cell repletion especially in patients with opportunistic or recurrent infections. Fetal Risk: May cause fetal harm based on animal data. Advise females of reproductive potential of the potential risk to a fetus and to use an effective method of contraception during treatment and for 6 months after stopping UPLIZNA. Adverse Reactions: The most common adverse reactions (at least 10% of patients treated with UPLIZNA and greater than placebo) were urinary tract infection and arthralgia. For additional information on UPLIZNA, please see the Full Prescribing Information at www.UPLIZNA.com . About Amgen Amgen discovers, develops, manufactures, and delivers innovative medicines to help millions of patients in their fight against some of the world's toughest diseases. More than 40 years ago, Amgen helped to establish the biotechnology industry and remains on the cutting-edge of innovation, using technology and human genetic data to push beyond what's known today. Amgen is advancing a broad and deep pipeline that builds on its existing portfolio of medicines to treat cancer, heart disease, osteoporosis, inflammatory diseases and rare diseases. In 2024, Amgen was named one of the "World's Most Innovative Companies" by Fast Company and one of "America's Best Large Employers" by Forbes, among other external recognitions . Amgen is one of the 30 companies that comprise the Dow Jones Industrial Average ® , and it is also part of the Nasdaq-100 Index ® , which includes the largest and most innovative non-financial companies listed on the Nasdaq Stock Market based on market capitalization. For more information, visit Amgen.com and follow Amgen on X , LinkedIn , Instagram , TikTok , YouTube and Threads . Forward-Looking Statements This news release contains forward-looking statements that are based on the current expectations and beliefs of Amgen . All statements, other than statements of historical fact, are statements that could be deemed forward-looking statements, including any statements on the outcome, benefits and synergies of collaborations, or potential collaborations, with any other company (including BeiGene, Ltd. or Kyowa Kirin Co., Ltd.), the performance of Otezla ® (apremilast) (including anticipated Otezla sales growth and the timing of non-GAAP EPS accretion), our acquisitions of Teneobio, Inc. , ChemoCentryx, Inc. , or Horizon Therapeutics plc (including the prospective performance and outlook of Horizon's business, performance and opportunities, any potential strategic benefits, synergies or opportunities expected as a result of such acquisition, and any projected impacts from the Horizon acquisition on our acquisition-related expenses going forward), as well as estimates of revenues, operating margins, capital expenditures, cash, other financial metrics, expected legal, arbitration, political, regulatory or clinical results or practices, customer and prescriber patterns or practices, reimbursement activities and outcomes, effects of pandemics or other widespread health problems on our business, outcomes, progress, and other such estimates and results. Forward-looking statements involve significant risks and uncertainties, including those discussed below and more fully described in the Securities and Exchange Commission reports filed by Amgen , including our most recent annual report on Form 10-K and any subsequent periodic reports on Form 10-Q and current reports on Form 8-K. Unless otherwise noted, Amgen is providing this information as of the date of this news release and does not undertake any obligation to update any forward-looking statements contained in this document as a result of new information, future events or otherwise. No forward-looking statement can be guaranteed and actual results may differ materially from those we project. Discovery or identification of new product candidates or development of new indications for existing products cannot be guaranteed and movement from concept to product is uncertain; consequently, there can be no guarantee that any particular product candidate or development of a new indication for an existing product will be successful and become a commercial product. Further, preclinical results do not guarantee safe and effective performance of product candidates in humans. The complexity of the human body cannot be perfectly, or sometimes, even adequately modeled by computer or cell culture systems or animal models. The length of time that it takes for us to complete clinical trials and obtain regulatory approval for product marketing has in the past varied and we expect similar variability in the future. Even when clinical trials are successful, regulatory authorities may question the sufficiency for approval of the trial endpoints we have selected. 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An outbreak of disease or similar public health threat, such as COVID-19, and the public and governmental effort to mitigate against the spread of such disease, could have a significant adverse effect on the supply of materials for our manufacturing activities, the distribution of our products, the commercialization of our product candidates, and our clinical trial operations, and any such events may have a material adverse effect on our product development, product sales, business and results of operations. We rely on collaborations with third parties for the development of some of our product candidates and for the commercialization and sales of some of our commercial products. In addition, we compete with other companies with respect to many of our marketed products as well as for the discovery and development of new products. Further, some raw materials, medical devices and component parts for our products are supplied by sole third-party suppliers. Certain of our distributors, customers and payers have substantial purchasing leverage in their dealings with us. The discovery of significant problems with a product similar to one of our products that implicate an entire class of products could have a material adverse effect on sales of the affected products and on our business and results of operations. Our efforts to collaborate with or acquire other companies, products or technology, and to integrate the operations of companies or to support the products or technology we have acquired, may not be successful. There can be no guarantee that we will be able to realize any of the strategic benefits, synergies or opportunities arising from the Horizon acquisition, and such benefits, synergies or opportunities may take longer to realize than expected. We may not be able to successfully integrate Horizon, and such integration may take longer, be more difficult or cost more than expected. A breakdown, cyberattack or information security breach of our information technology systems could compromise the confidentiality, integrity and availability of our systems and our data. Our stock price is volatile and may be affected by a number of events. Our business and operations may be negatively affected by the failure, or perceived failure, of achieving our environmental, social and governance objectives. The effects of global climate change and related natural disasters could negatively affect our business and operations. Global economic conditions may magnify certain risks that affect our business. Our business performance could affect or limit the ability of our Board of Directors to declare a dividend or our ability to pay a dividend or repurchase our common stock. We may not be able to access the capital and credit markets on terms that are favorable to us, or at all. Any scientific information discussed in this news release relating to new indications for our products is preliminary and investigative and is not part of the labeling approved by the U.S. Food and Drug Administration for the products. The products are not approved for the investigational use(s) discussed in this news release, and no conclusions can or should be drawn regarding the safety or effectiveness of the products for these uses. CONTACT: Amgen, Thousand Oaks Madison Howard , 773-636-4910 (media) Elissa Snook , 609-251-1407 (media) Justin Claeys , 805-313-9775 (investors) References View original content to download multimedia: https://www.prnewswire.com/news-releases/amgen-presents-positive-phase-3-data-for-uplizna-inebilizumab-cdon-in-generalized-myasthenia-gravis-gmg-at-aanem-2024-302275645.html SOURCE Amgen

Infusion related reactions in patients receiving 30-minute BRIUMVI infusions were all mild (Grade 1) and resolved completely Data also demonstrate patients switching from prior anti-CD20 treatment can successfully eliminate initial BRIUMVI infusion NEW YORK, Sept. 18, 2024 (GLOBE NEWSWIRE) -- TG Therapeutics, Inc. (NASDAQ: TGTX), today presented updated data from the ENHANCE Phase 3b trial evaluating BRIUMVI® (ublituximab-xiiy) in patients with relapsing forms of multiple sclerosis (RMS), at the 2024 European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) annual meeting. Highlights from the presentation are outlined below. Michael S. Weiss, the Company’s Chairman and Chief Executive Officer stated, “We are excited to present an update from our ENHANCE Phase 3b study which is evaluating potential optimized dosing regimens for BRIUMVI. This study initially focused on patients switching from a prior anti-CD20 therapy in a B-cell depleted state, and we believe the data emerging from this study continues to support that these patients can successfully make that transition conveniently and safely without the initial 150 mg, 4-hour BRIUMVI infusion.” Mr. Weiss continued, “Separately, we are excited to present, for the first time, data exploring even faster infusions of BRIUMVI, from 1 hour down to 30 minutes for full doses starting at week 24. Notably, these rapid infusions are being accomplished with non-drowsy pre-medications and no required post-infusion observation time as per the protocol, consistent with the BRIUMVI prescribing information. We look forward to continuing to find ways to improve patient tolerability and convenience and working with regulatory agencies to transition these efforts into label-enabling studies.” DATA HIGHLIGHTS:Poster Presentation: Efficacy and Tolerability of BRIUMVI (ublituximab) after Transitioning from a Different Disease-Modifying Therapy: Updates from the ENHANCE Study ENHANCE is a multi-center, open-label, 48-week study in participants with relapsing forms of multiple sclerosis (RMS) designed to evaluate optimized dosing regimens for BRIUMVI with two primary objectives: Evaluating the elimination of the initial 150 mg BRIUMVI infusion in patients who are B-cell depletedExploring shorter infusion durations for the full 450 mg BRIUMVI infusions Data continue to support that 450 mg of BRIUMVI may be safely administered in 1 hour as an initial infusion for participants who are B-cell depleted, with 97% of infusions being completed without interruption or slowing12 patients received 450 mg BRIUMVI infusions in 30 minutes at week 24, with all infusions completed without interruption or slowing, and infusions related reactions (IRRs) were limited to Grade 1 (n=2) The data presentation is also available on the Publications page, located within the Pipeline section, of the Company’s website at www.tgtherapeutics.com/publications.cfm. ABOUT THE ULTIMATE I & II PHASE 3 TRIALSULTIMATE I & II are two randomized, double-blind, double-dummy, parallel group, active comparator-controlled clinical trials of identical design, in patients with RMS treated for 96 weeks. Patients were randomized to receive either BRIUMVI, given as an IV infusion of 150 mg administered in four hours, 450 mg two weeks after the first infusion administered in one hour, and 450 mg every 24 weeks administered in one hour, with oral placebo administered daily; or teriflunomide, the active comparator, given orally as a 14 mg daily dose with IV placebo administered on the same schedule as BRIUMVI. Both studies enrolled patients who had experienced at least one relapse in the previous year, two relapses in the previous two years, or had the presence of a T1 gadolinium (Gd)-enhancing lesion in the previous year. Patients were also required to have an Expanded Disability Status Scale (EDSS) score from 0 to 5.5 at baseline. The ULTIMATE I & II trials enrolled a total of 1,094 patients with RMS across 10 countries. These trials were led by Lawrence Steinman, MD, Zimmermann Professor of Neurology & Neurological Sciences, and Pediatrics at Stanford University. Additional information on these clinical trials can be found at http://www.clinicaltrials.gov (NCT03277261; NCT03277248). ABOUT BRIUMVI® (ublituximab-xiiy) 150 mg/6 mL Injection for IVBRIUMVI is a novel monoclonal antibody that targets a unique epitope on CD20-expressing B-cells. Targeting CD20 using monoclonal antibodies has proven to be an important therapeutic approach for the management of autoimmune disorders, such as RMS. BRIUMVI is uniquely designed to lack certain sugar molecules normally expressed on the antibody. Removal of these sugar molecules, a process called glycoengineering, allows for efficient B-cell depletion at low doses. BRIUMVI is indicated for the treatment of adults with relapsing forms of multiple sclerosis (RMS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease. A list of authorized specialty distributors can be found at www.briumvi.com. IMPORTANT SAFETY INFORMATIONContraindications: BRIUMVI is contraindicated in patients with: Active Hepatitis B Virus infectionA history of life-threatening infusion reaction to BRIUMVI WARNINGS AND PRECAUTIONS Infusion Reactions: BRIUMVI can cause infusion reactions, which can include pyrexia, chills, headache, influenza-like illness, tachycardia, nausea, throat irritation, erythema, and an anaphylactic reaction. In MS clinical trials, the incidence of infusion reactions in BRIUMVI-treated patients who received infusion reaction-limiting premedication prior to each infusion was 48%, with the highest incidence within 24 hours of the first infusion. 0.6% of BRIUMVI-treated patients experienced infusion reactions that were serious, some requiring hospitalization. Observe treated patients for infusion reactions during the infusion and for at least one hour after the completion of the first two infusions unless infusion reaction and/or hypersensitivity has been observed in association with the current or any prior infusion. Inform patients that infusion reactions can occur up to 24 hours after the infusion. Administer the recommended pre-medication to reduce the frequency and severity of infusion reactions. If life-threatening, stop the infusion immediately, permanently discontinue BRIUMVI, and administer appropriate supportive treatment. Less severe infusion reactions may involve temporarily stopping the infusion, reducing the infusion rate, and/or administering symptomatic treatment. Infections: Serious, life-threatening or fatal, bacterial and viral infections have been reported in BRIUMVI-treated patients. In MS clinical trials, the overall rate of infections in BRIUMVI-treated patients was 56% compared to 54% in teriflunomide-treated patients. The rate of serious infections was 5% compared to 3% respectively. There were 3 infection-related deaths in BRIUMVI-treated patients. The most common infections in BRIUMVI-treated patients included upper respiratory tract infection (45%) and urinary tract infection (10%). Delay BRIUMVI administration in patients with an active infection until the infection is resolved. Consider the potential for increased immunosuppressive effects when initiating BRIUMVI after immunosuppressive therapy or initiating an immunosuppressive therapy after BRIUMVI. Hepatitis B Virus (HBV) Reactivation: HBV reactivation occurred in an MS patient treated with BRIUMVI in clinical trials. Fulminant hepatitis, hepatic failure, and death caused by HBV reactivation have occurred in patients treated with anti-CD20 antibodies. Perform HBV screening in all patients before initiation of treatment with BRIUMVI. Do not start treatment with BRIUMVI in patients with active HBV confirmed by positive results for HBsAg and anti-HB tests. For patients who are negative for surface premedantigen [HBsAg] and positive for HB core antibody [HBcAb+] or are carriers of HBV [HBsAg+], consult a liver disease expert before starting and during treatment. Progressive Multifocal Leukoencephalopathy (PML): Although no cases of PML have occurred in BRIUMVI-treated MS patients, JCV infection resulting in PML has been observed in patients treated with other anti-CD20 antibodies and other MS therapies. If PML is suspected, withhold BRIUMVI and perform an appropriate diagnostic evaluation. Typical symptoms associated with PML are diverse, progress over days to weeks, and include progressive weakness on one side of the body or clumsiness of limbs, disturbance of vision, and changes in thinking, memory, and orientation leading to confusion and personality changes. MRI findings may be apparent before clinical signs or symptoms; monitoring for signs consistent with PML may be useful. Further investigate suspicious findings to allow for an early diagnosis of PML, if present. Following discontinuation of another MS medication associated with PML, lower PML-related mortality and morbidity have been reported in patients who were initially asymptomatic at diagnosis compared to patients who had characteristic clinical signs and symptoms at diagnosis. If PML is confirmed, treatment with BRIUMVI should be discontinued. Vaccinations: Administer all immunizations according to immunization guidelines: for live or live-attenuated vaccines at least 4 weeks and, whenever possible at least 2 weeks prior to initiation of BRIUMVI for non-live vaccines. BRIUMVI may interfere with the effectiveness of non-live vaccines. The safety of immunization with live or live-attenuated vaccines during or following administration of BRIUMVI has not been studied. Vaccination with live virus vaccines is not recommended during treatment and until B-cell repletion. Vaccination of Infants Born to Mothers Treated with BRIUMVI During Pregnancy: In infants of mothers exposed to BRIUMVI during pregnancy, assess B-cell counts prior to administration of live or live-attenuated vaccines as measured by CD19+ B-cells. Depletion of B-cells in these infants may increase the risks from live or live-attenuated vaccines. Inactivated or non-live vaccines may be administered prior to B-cell recovery. Assessment of vaccine immune responses, including consultation with a qualified specialist, should be considered to determine whether a protective immune response was mounted. Fetal Risk: Based on data from animal studies, BRIUMVI may cause fetal harm when administered to a pregnant woman. Transient peripheral B-cell depletion and lymphocytopenia have been reported in infants born to mothers exposed to other anti-CD20 B-cell depleting antibodies during pregnancy. A pregnancy test is recommended in females of reproductive potential prior to each infusion. Advise females of reproductive potential to use effective contraception during BRIUMVI treatment and for 6 months after the last dose. Reduction in Immunoglobulins: As expected with any B-cell depleting therapy, decreased immunoglobulin levels were observed. Decrease in immunoglobulin M (IgM) was reported in 0.6% of BRIUMVI-treated patients compared to none of the patients treated with teriflunomide in RMS clinical trials. Monitor the levels of quantitative serum immunoglobulins during treatment, especially in patients with opportunistic or recurrent infections, and after discontinuation of therapy until B-cell repletion. Consider discontinuing BRIUMVI therapy if a patient with low immunoglobulins develops a serious opportunistic infection or recurrent infections, or if prolonged hypogammaglobulinemia requires treatment with intravenous immunoglobulins. Most Common Adverse Reactions: The most common adverse reactions in RMS trials (incidence of at least 10%) were infusion reactions and upper respiratory tract infections. Physicians, pharmacists, or other healthcare professionals with questions about BRIUMVI should visit www.briumvi.com. ABOUT BRIUMVI PATIENT SUPPORT BRIUMVI Patient Support is a flexible program designed by TG Therapeutics to support U.S. patients through their treatment journey in a way that works best for them. More information about the BRIUMVI Patient Support program can be accessed at www.briumvipatientsupport.com. ABOUT MULTIPLE SCLEROSIS Relapsing multiple sclerosis (RMS) is a chronic demyelinating disease of the central nervous system (CNS) and includes people with relapsing-remitting multiple sclerosis (RRMS) and people with secondary progressive multiple sclerosis (SPMS) who continue to experience relapses. RRMS is the most common form of multiple sclerosis (MS) and is characterized by episodes of new or worsening signs or symptoms (relapses) followed by periods of recovery. It is estimated that nearly 1 million people are living with MS in the United States and approximately 85% are initially diagnosed with RRMS.1,2 The majority of people who are diagnosed with RRMS will eventually transition to SPMS, in which they experience steadily worsening disability over time. Worldwide, more than 2.3 million people have a diagnosis of MS.1 ABOUT TG THERAPEUTICSTG Therapeutics is a fully integrated, commercial stage, biopharmaceutical company focused on the acquisition, development and commercialization of novel treatments for B-cell diseases. In addition to a research pipeline including several investigational medicines, TG has received U.S. Food and Drug Administration (FDA) approval for BRIUMVI® (ublituximab-xiiy), for the treatment of adult patients with relapsing forms of multiple sclerosis (RMS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, as well as approval by the European Commission (EC) and the Medicines and Healthcare Products Regulatory Agency (MHRA) for BRIUMVI to treat adult patients with RMS who have active disease defined by clinical or imaging features in Europe and the United Kingdom, respectively. For more information, visit www.tgtherapeutics.com, and follow us on X (formerly Twitter) @TGTherapeutics and on LinkedIn. BRIUMVI® is a registered trademark of TG Therapeutics, Inc. Cautionary StatementThis press release contains forward-looking statements that involve a number of risks and uncertainties. For those statements, we claim the protection of the safe harbor for forward-looking statements contained in the Private Securities Litigation Reform Act of 1995. Any forward-looking statements in this press release are based on management's current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this press release. In addition to the risk factors identified from time to time in our reports filed with the U.S. Securities and Exchange Commission (SEC), factors that could cause our actual results to differ materially include the below. Such forward looking statements include but are not limited to statements regarding the results of the ULTIMATE I & II Phase 3 studies, the ENHANCE Phase 3b study, and BRIUMVI as a treatment for relapsing forms of multiple sclerosis (RMS). Additional factors that could cause our actual results to differ materially include the following: the risk that the data from the ULTIMATE I & II and its Open-Label Extension (OLE) or ENHANCE trials that we announce or publish may change, or the product profile of BRIUMVI may be impacted, as more data or additional endpoints are analyzed; the risk that the dose-optimization efforts being undertaken in ENHANCE will not transition into label-enabling studies, or that any label-enabling efforts may be unsuccessful; the risk that data may emerge from future clinical studies or from adverse event reporting that may affect the safety and tolerability profile and commercial potential of BRIUMVI; the risk that any individual patient’s clinical experience in the post-marketing setting, or the aggregate patient experience in the post-marketing setting, may differ from that demonstrated in controlled clinical trials such as ULTIMATE I and II; the risk that BRIUMVI will not be commercially successful; our ability to expand our commercial infrastructure, and successfully market and sell BRIUMVI in RMS; the Company’s reliance on third parties for manufacturing, distribution and supply, and a range of other support functions for our commercial and clinical products, including BRIUMVI, and the ability of the Company and its manufacturers and suppliers to produce and deliver BRIUMVI to meet the market demand for BRIUMVI; the failure to obtain and maintain requisite regulatory approvals, including the risk that the Company fails to satisfy post-approval regulatory requirements; the uncertainties inherent in research and development; and general political, economic and business conditions, including the risk that the ongoing COVID-19 pandemic could have on the safety profile of BRIUMVI and any of our other drug candidates as well as any government control measures associated with COVID-19 that could have an adverse impact on our research and development plans or commercialization efforts. Further discussion about these and other risks and uncertainties can be found in our Annual Report on Form 10-K for the fiscal year ended December 31, 2023 and in our other filings with the U.S. Securities and Exchange Commission. Any forward-looking statements set forth in this press release speak only as of the date of this press release. We do not undertake to update any of these forward-looking statements to reflect events or circumstances that occur after the date hereof. This press release and prior releases are available at www.tgtherapeutics.com. The information found on our website is not incorporated by reference into this press release and is included for reference purposes only. CONTACT: Investor Relations Email: ir@tgtxinc.comTelephone: 1.877.575.TGTX (8489), Option 4 Media Relations: Email: media@tgtxinc.com Telephone: 1.877.575.TGTX (8489), Option 6 1. MS Prevalence. National Multiple Sclerosis Society website. https://www.nationalmssociety.org/About-the-Society/MS-Prevalence. Accessed October 26, 2020. 2. Multiple Sclerosis International Federation, 2013 via Datamonitor p. 236.