Phenytoin

PRINCETON, N.J.--( BUSINESS WIRE )-- Bristol Myers Squibb (NYSE: BMY) today announced the presentation of research across its robust cardiovascular portfolio at the European Society of Cardiology (ESC) Congress, taking place August 30 – September 2, 2024, in London, England. Data to be presented at the meeting includes long-term extension data evaluating the efficacy and safety profile of CAMZYOS ® (mavacamten) up to 180 weeks (3.5 years) for the treatment of New York Heart Association (NYHA) class II-III symptomatic obstructive hypertrophic cardiomyopathy (oHCM), as well as data on behalf of the BMS-Pfizer Alliance on ELIQUIS ® (apixaban) and the BMS-Johnson & Johnson Collaboration on milvexian. “With the data to be presented from our cardiovascular franchise at this year’s ESC Congress, we continue to demonstrate our longstanding and unwavering commitment to improving the lives of patients impacted by cardiovascular diseases,” said Roland Chen, MD , senior vice president and head of Immunology, Cardiovascular & Neuroscience (ICN) Development at Bristol Myers Squibb. “We look forward to showcasing how we’re advancing development of our medicines for anticoagulation and thrombosis management as well as for the treatment of obstructive HCM for patients in need at the upcoming meeting.” Key presentations include: An oral presentation highlighting long-term efficacy and safety of CAMZYOS in NYHA class II-III obstructive HCM up to 180 weeks (nearly 3.5 years), an unprecedented follow-up duration for patients using the first and only approved cardiac myosin inhibitor for oHCM (EXPLORER Ph3 MAVA LTE study). A moderated poster presentation characterizing the relationship between key pharmacodynamic biomarkers of coagulation and systemic milvexian exposure in patients from the AXIOMATIC-TKR study. A moderated poster presentation spotlighting the gender and racial differences in clinical outcomes among Medicare beneficiaries with non-valvular atrial fibrillation (NVAF) treated with oral anticoagulants, including ELIQUIS. Select abstracts sponsored by Bristol Myers Squibb, BMS-Pfizer Alliance and BMS-Johnson & Johnson Collaboration to be presented at ESC Congress 2024 can be found below. Complete abstracts may be accessed online here . Visit this page on BMS.com for more information on Bristol Myers Squibb’s scientific approach and resources on cardiovascular diseases. Abstract Title Primary Author Type Session Title Date/Time (BST) CAMZYOS (mavacamten) Assessing the alignment of obstructive hypertrophic cardiomyopathy pharmacological treatments with ESC guidelines in Germany Sedaghat-Hamedani, F Moderated Poster HOCM - clearing the roadblock Friday, Aug. 30 13:00 Clinical characteristics and burden of non-obstructive hypertrophic cardiomyopathy: a real-world survey in Italy and Spain Lowe, M Moderated Poster Hypertrophic and other cardiomyopathies: misc findings Saturday, Aug. 31 13:00 Long-term safety and efficacy of mavacamten in obstructive hypertrophic cardiomyopathy: up to 3.5-year follow-up results of the EXPLORER cohort of MAVA-Long-Term Extension study Garcia-Pavia, P Oral Presentation Novel therapies for hypertrophic cardiomyopathy - recent developments and future prospects Sunday, Sept. 1 08:33 Serial changes in left and right ventricular global longitudinal strain in symptomatic obstructive hypertrophic cardiomyopathy treated with mavacamten: Insights from VALOR-HCM trial Desai, M Oral Presentation Cardiac myosin inhibitors for treatment of hypertrophic obstructive cardiomyopathy Monday, Sept. 2 12:20 Serial changes in left atrial strain in symptomatic obstructive hypertrophic cardiomyopathy treated with mavacamten: Insights from VALOR-HCM trial Desai, M Oral Presentation New imaging insights into hypertrophic cardiomyopathy Monday, Sept. 2 14:03 ELIQUIS (apixaban) Gender and racial differences in outcomes among patients with NVAF treated with oral anticoagulants: a real-world evaluation of Medicare beneficiaries* Atreja, N Moderated Poster Antithrombotic and anticoagulant therapy in social Friday, Aug. 30 16:00 A novel dynamic risk score to predict venous thromboembolism (VTE) recurrences after 3 months of anticoagulation in patients with incident VTE and without active cancer* Cohen, AT Moderated Poster Pearls of acute pulmonary embolism Friday, Aug. 30 17:00 The incidence of cardiovascular conditions in patients admitted to hospital with and without COVID-19 in the South-East of Scotland* Bulgara, A Moderated Poster New considerations in acute coronary syndromes Sunday, Sept. 1 10:00 GUARD-AF - Reducing stroke by screening for undiagnosed atrial fibrillation in elderly individuals* Lopes, R Late- breaking Oral Presentation HOT LINE 9 Sunday, Sept. 1 17:50 A novel dynamic risk score to predict clinically significant bleeding (CSB) after 3 months of anticoagulation in patients with incident venous thromboembolism (VTE) and without active cancer* Choudhuri, S Moderated Poster Venous thromboembolism – international perspectives Monday, Sept. 2 09:00 Milvexian Characterisation of the pharmacokinetic and pharmacodynamic relationship of milvexian in total knee replacement patients † Zhou, W Moderated Poster Novel anticoagulants and indications Monday, Sept. 2 13:00 *Sponsored by the Bristol Myers Squibb-Pfizer Alliance † Sponsored by the Bristol Myers Squibb-Johnson & Johnson Collaboration About Milvexian ‡ Milvexian is an investigational, oral factor XIa (FXIa) inhibitor (anticoagulant) being studied for the prevention and treatment of major thrombotic conditions as part of the Phase 3 Librexia program, the most comprehensive FXIa clinical development program to date. ‡ Milvexian is an investigational agent and has not been approved for use in any country, for any indication. About the Bristol Myers Squibb-Johnson & Johnson Collaboration Bristol Myers Squibb and Johnson & Johnson, two unsurpassed leaders in cardiovascular care, are determined to close the gap in unmet needs in thrombosis management by overcoming the limits of today’s treatments. The collaboration to develop and commercialize milvexian aims to leverage the combined scientific expertise and world-class commercial capabilities of each company, to improve patient outcomes. The alliance is uniquely equipped to deliver on the promise of FXIa inhibitors and is working diligently to ensure cutting-edge safe and effective treatment options are available for patients. About CAMZYOS ® (mavacamten) CAMZYOS ® (mavacamten) is the first and only cardiac myosin inhibitor approved in the U.S., indicated for the treatment of adults with symptomatic New York Heart Association (NYHA) class II-III obstructive hypertrophic cardiomyopathy (oHCM) to improve functional capacity and symptoms, and in the European Union, indicated for the treatment of symptomatic (NYHA, class II-III) obstructive HCM in adult patients. It has also received regulatory approvals in countries and regions across five continents including Argentina, Australia, Brazil, Canada, China, Chile, Great Britain, Hong Kong, Israel, Macau, Singapore, South Korea, Switzerland, and the United Arab Emirates. CAMZYOS is an allosteric and reversible inhibitor selective for cardiac myosin. CAMZYOS modulates the number of myosin heads that can enter “on actin” (power-generating) states, thus reducing the probability of force-producing (systolic) and residual (diastolic) cross-bridge formation. Excess myosin actin cross-bridge formation and dysregulation of the super-relaxed state are mechanistic hallmarks of HCM. CAMZYOS shifts the overall myosin population towards an energy-sparing, recruitable, super-relaxed state. In HCM patients, myosin inhibition with CAMZYOS reduces dynamic left ventricular outflow tract (LVOT) obstruction and improves cardiac filling pressures. IMPORTANT SAFETY INFORMATION WARNING: RISK OF HEART FAILURE CAMZYOS reduces left ventricular ejection fraction (LVEF) and can cause heart failure due to systolic dysfunction. Echocardiogram assessments of LVEF are required prior to and during treatment with CAMZYOS. Initiation of CAMZYOS in patients with LVEF <55% is not recommended. Interrupt CAMZYOS if LVEF is <50% at any visit or if the patient experiences heart failure symptoms or worsening clinical status. Concomitant use of CAMZYOS with certain cytochrome P450 inhibitors or discontinuation of certain cytochrome P450 inducers may increase the risk of heart failure due to systolic dysfunction; therefore, the use of CAMZYOS is contraindicated with the following: Moderate to strong CYP2C19 inhibitors or strong CYP3A4 inhibitors Moderate to strong CYP2C19 inducers or moderate to strong CYP3A4 inducers Because of the risk of heart failure due to systolic dysfunction, CAMZYOS is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the CAMZYOS REMS PROGRAM. CONTRAINDICATIONS CAMZYOS is contraindicated with concomitant use of: Moderate to strong CYP2C19 inhibitors or strong CYP3A4 inhibitors Moderate to strong CYP2C19 inducers or moderate to strong CYP3A4 inducers WARNINGS AND PRECAUTIONS Heart Failure CAMZYOS reduces systolic contraction and can cause heart failure or totally block ventricular function. Patients who experience a serious intercurrent illness (e.g., serious infection) or arrhythmia (e.g., atrial fibrillation or other uncontrolled tachyarrhythmia) are at greater risk of developing systolic dysfunction and heart failure. Assess the patient’s clinical status and LVEF prior to and regularly during treatment and adjust the CAMZYOS dose accordingly. New or worsening arrhythmia, dyspnea, chest pain, fatigue, palpitations, leg edema, or elevations in N-terminal pro-B-type natriuretic peptide (NT-proBNP) may be signs and symptoms of heart failure and should also prompt an evaluation of cardiac function. Asymptomatic LVEF reduction, intercurrent illnesses, and arrhythmias require additional dosing considerations. Initiation of CAMZYOS in patients with LVEF <55% is not recommended. Avoid concomitant use of CAMZYOS in patients on disopyramide, ranolazine, verapamil with a beta blocker, or diltiazem with a beta blocker as these medications and combinations increase the risk of left ventricular systolic dysfunction and heart failure symptoms and clinical experience is limited. CYP 450 Drug Interactions Leading to Heart Failure or Loss of Effectiveness CAMZYOS is primarily metabolized by CYP2C19 and CYP3A4 enzymes. Concomitant use of CAMZYOS and drugs that interact with these enzymes may lead to life-threatening drug interactions such as heart failure or loss of effectiveness. Advise patients of the potential for drug interactions, including with over-the-counter medications (such as omeprazole, esomeprazole, or cimetidine). Advise patients to inform their healthcare provider of all concomitant products prior to and during CAMZYOS treatment. CAMZYOS Risk Evaluation and Mitigation Strategy (REMS) Program CAMZYOS is only available through a restricted program called the CAMZYOS REMS Program because of the risk of heart failure due to systolic dysfunction. Notable requirements of the CAMZYOS REMS Program include the following: Prescribers must be certified by enrolling in the REMS Program. Patients must enroll in the REMS Program and comply with ongoing monitoring requirements. Pharmacies must be certified by enrolling in the REMS Program and must only dispense to patients who are authorized to receive CAMZYOS. Wholesalers and distributors must only distribute to certified pharmacies. Further information is available at www.CAMZYOSREMS.com or by telephone at 1-833-628-7367. Embryo-Fetal Toxicity CAMZYOS may cause fetal toxicity when administered to a pregnant female, based on animal studies. Confirm absence of pregnancy in females of reproductive potential prior to treatment and advise patients to use effective contraception during treatment with CAMZYOS and for 4 months after the last dose. CHCs containing a combination of ethinyl estradiol and norethindrone may be used with CAMZYOS. However, CAMZYOS may reduce the effectiveness of combined hormonal contraceptives (CHC). If these CHCs are used, advise patients to add nonhormonal contraception (such as condoms) during concomitant use and for 4 months after the last dose of CAMZYOS. ADVERSE REACTIONS In the EXPLORER-HCM trial, adverse reactions occurring in >5% of patients and more commonly in the CAMZYOS group than in the placebo group were dizziness (27% vs 18%) and syncope (6% vs 2%). There were no new adverse reactions identified in VALOR-HCM. Effects on Systolic Function In the EXPLORER-HCM trial, mean (SD) resting LVEF was 74% (6) at baseline in both treatment groups. Mean (SD) absolute change from baseline in LVEF was -4% (8) in the CAMZYOS group and 0% (7) in the placebo group over the 30-week treatment period. At Week 38, following an 8-week interruption of trial drug, mean LVEF was similar to baseline for both treatment groups. In the EXPLORER-HCM trial, 7 (6%) patients in the CAMZYOS group and 2 (2%) patients in the placebo group experienced reversible reductions in LVEF <50% (median 48%: range 35-49%) while on treatment. In all 7 patients treated with CAMZYOS, LVEF recovered following interruption of CAMZYOS. DRUG INTERACTIONS Potential for Other Drugs to Affect Plasma Concentrations of CAMZYOS CAMZYOS is primarily metabolized by CYP2C19 and to a lesser extent by CYP3A4 and CYP2C9. Inducers and inhibitors of CYP2C19 and moderate to strong inhibitors or inducers of CYP3A4 may affect the exposures of CAMZYOS. Impact of Other Drugs on CAMZYOS: Moderate to Strong CYP2C19 Inhibitors or Strong CYP3A4 Inhibitors : Concomitant use increases CAMZYOS exposure, which may increase the risk of heart failure due to systolic dysfunction. Concomitant use is contraindicated. Moderate to Strong CYP2C19 Inducers or Moderate to Strong CYP3A4 Inducers : Concomitant use decreases CAMZYOS exposure, which may reduce CAMZYOS’ efficacy. The risk of heart failure due to systolic dysfunction may increase with discontinuation of these inducers as the levels of induced enzyme normalizes. Concomitant use is contraindicated. Weak CYP2C19 Inhibitors or Moderate CYP3A4 Inhibitors : Concomitant use with a weak CYP2C19 inhibitor or a moderate CYP3A4 inhibitor increases CAMZYOS exposure, which may increase the risk of adverse drug reactions. Initiate CAMZYOS at the recommended starting dose of 5 mg orally once daily in patients who are on stable therapy with a weak CYP2C19 inhibitor or a moderate CYP3A4 inhibitor. Reduce dose of CAMZYOS by one level (i.e., 15 to 10 mg, 10 to 5 mg, or 5 to 2.5 mg) in patients who are on CAMZYOS treatment and intend to initiate a weak CYP2C19 inhibitor or a moderate CYP3A4 inhibitor. Schedule clinical and echocardiographic assessment 4 weeks after inhibitor initiation, and do not up-titrate CAMZYOS until 12 weeks after inhibitor initiation. Avoid initiation of concomitant weak CYP2C19 and moderate CYP3A4 inhibitors in patients who are on stable treatment with 2.5 mg of CAMZYOS because a lower dose is not available. Potential for CAMZYOS to Affect Plasma Concentrations of Other Drugs CAMZYOS is an inducer of CYP3A4, CYP2C9, and CYP2C19. Concomitant use with CYP3A4, CYP2C19, or CYP2C9 substrates may reduce plasma concentration of these drugs. Closely monitor when CAMZYOS is used in combination with CYP3A4, CYP2C19, or CYP2C9 substrates unless otherwise recommended in the Prescribing Information. Certain Combined Hormonal Contraceptives (CHC): Progestin and ethinyl estradiol are CYP3A4 substrates. Concomitant use of CAMZYOS may decrease exposures of certain progestins, which may lead to contraceptive failure. CHCs containing a combination of ethinyl estradiol and norethindrone may be used with CAMZYOS, but if other CHCs are used, advise patients to add nonhormonal contraception (such as condoms) during concomitant use and for 4 months after the last dose of CAMZYOS. Drugs That Reduce Cardiac Contractility Expect additive negative inotropic effects of CAMZYOS and other drugs that reduce cardiac contractility. Avoid concomitant use of CAMZYOS in patients on disopyramide, ranolazine, verapamil with a beta blocker, or diltiazem with a beta blocker as these medications and combinations increase the risk of left ventricular systolic dysfunction and heart failure symptoms and clinical experience is limited. If concomitant therapy with a negative inotrope is initiated, or if the dose of a negative inotrope is increased, monitor LVEF closely until stable doses and clinical response have been achieved. SPECIFIC POPULATIONS Pregnancy CAMZYOS may cause fetal harm when administered to a pregnant female. Advise pregnant females about the potential risk to the fetus with maternal exposure to CAMZYOS during pregnancy. There is a pregnancy safety study for CAMZYOS. If CAMZYOS is administered during pregnancy, or if a patient becomes pregnant while receiving CAMZYOS or within 4 months after the last dose of CAMZYOS, healthcare providers should report CAMZYOS exposure by contacting Bristol Myers Squibb at 1-800-721-5072 or www.bms.com . Lactation The presence of CAMZYOS in human or animal milk, the drug’s effects on the breastfed infant, or the effects on milk production are unknown. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for CAMZYOS and any potential adverse effects on the breastfed child from CAMZYOS or from the underlying maternal condition. Females and Males of Reproductive Potential Confirm absence of pregnancy in females of reproductive potential prior to initiation of CAMZYOS. Advise females of reproductive potential to use effective contraception during treatment with CAMZYOS and for 4 months after the last dose. CHCs containing a combination of ethinyl estradiol and norethindrone may be used with CAMZYOS. However, CAMZYOS may reduce the effectiveness of certain other combined hormonal contraceptives (CHC). If these CHCs are used, advise patients to add nonhormonal contraception (such as condoms) during concomitant use and for 4 months after the last dose of CAMZYOS. Please see U.S. Full Prescribing Information , including Boxed WARNING and Medication Guide . About ELIQUIS ® (apixaban) ELIQUIS ® is an oral selective Factor Xa inhibitor. By inhibiting Factor Xa, a key blood clotting protein, ELIQUIS decreases thrombin generation and blood clot formation. ELIQUIS is approved for multiple indications in the U.S. based on efficacy and safety data from multiple Phase 3 clinical trials. ELIQUIS is a prescription medicine indicated to reduce the risk of stroke and systemic embolism in patients with non-valvular atrial fibrillation (NVAF); for the prophylaxis of deep vein thrombosis (DVT), which may lead to pulmonary embolism (PE), in patients who have undergone hip or knee replacement surgery; for the treatment of DVT and PE; and to reduce the risk of recurrent DVT and PE, following initial therapy. ELIQUIS continues to be developed and commercialized by The Bristol Myers Squibb-Pfizer Alliance. ELIQUIS Important Safety Information Indications ELIQUIS is indicated to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. ELIQUIS is indicated for the prophylaxis of deep vein thrombosis (DVT), which may lead to pulmonary embolism (PE), in patients who have undergone hip or knee replacement surgery. ELIQUIS is indicated for the treatment of DVT and PE, and to reduce the risk of recurrent DVT and PE following initial therapy. Important Safety Information WARNING: (A) PREMATURE DISCONTINUATION OF ELIQUIS INCREASES THE RISK OF THROMBOTIC EVENTS, (B) SPINAL/EPIDURAL HEMATOMA (A) Premature discontinuation of any oral anticoagulant, including ELIQUIS, increases the risk of thrombotic events. If anticoagulation with ELIQUIS is discontinued for a reason other than pathological bleeding or completion of a course of therapy, consider coverage with another anticoagulant. (B) Epidural or spinal hematomas may occur in patients treated with ELIQUIS who are receiving neuraxial anesthesia or undergoing spinal puncture. These hematomas may result in long-term or permanent paralysis. Consider these risks when scheduling patients for spinal procedures. Factors that can increase the risk of developing epidural or spinal hematomas in these patients include: use of indwelling epidural catheters concomitant use of other drugs that affect hemostasis, such as nonsteroidal anti-inflammatory drugs (NSAIDs), platelet inhibitors, other anticoagulants a history of traumatic or repeated epidural or spinal punctures a history of spinal deformity or spinal surgery optimal timing between the administration of ELIQUIS and neuraxial procedures is not known Monitor patients frequently for signs and symptoms of neurological impairment. If neurological compromise is noted, urgent treatment is necessary. Consider the benefits and risks before neuraxial intervention in patients anticoagulated or to be anticoagulated. CONTRAINDICATIONS Active pathological bleeding Severe hypersensitivity reaction to ELIQUIS (e.g., anaphylactic reactions) WARNINGS AND PRECAUTIONS Increased Risk of Thrombotic Events after Premature Discontinuation: Premature discontinuation of any oral anticoagulant, including ELIQUIS, in the absence of adequate alternative anticoagulation increases the risk of thrombotic events. An increased rate of stroke was observed during the transition from ELIQUIS to warfarin in clinical trials in atrial fibrillation patients. If ELIQUIS is discontinued for a reason other than pathological bleeding or completion of a course of therapy, consider coverage with another anticoagulant. Bleeding Risk: ELIQUIS increases the risk of bleeding and can cause serious, potentially fatal, bleeding. Concomitant use of drugs affecting hemostasis increases the risk of bleeding, including aspirin and other antiplatelet agents, other anticoagulants, heparin, thrombolytic agents, SSRIs, SNRIs, and NSAIDs. Advise patients of signs and symptoms of blood loss and to report them immediately or go to an emergency room. Discontinue ELIQUIS in patients with active pathological hemorrhage. The anticoagulant effect of apixaban can be expected to persist for at least 24 hours after the last dose (i.e., about two half-lives). An agent to reverse the anti-factor Xa activity of apixaban is available. Please visit www.andexxa.com for more information on availability of a specific reversal agent. Spinal/Epidural Anesthesia or Puncture: Patients treated with ELIQUIS undergoing spinal/epidural anesthesia or puncture may develop an epidural or spinal hematoma which can result in long-term or permanent paralysis. The risk of these events may be increased by the postoperative use of indwelling epidural catheters or the concomitant use of medicinal products affecting hemostasis. Indwelling epidural or intrathecal catheters should not be removed earlier than 24 hours after the last administration of ELIQUIS. The next dose of ELIQUIS should not be administered earlier than 5 hours after the removal of the catheter. The risk may also be increased by traumatic or repeated epidural or spinal puncture. If traumatic puncture occurs, delay the administration of ELIQUIS for 48 hours. Monitor patients frequently and if neurological compromise is noted, urgent diagnosis and treatment is necessary. Physicians should consider the potential benefit versus the risk of neuraxial intervention in ELIQUIS patients. Prosthetic Heart Valves: The safety and efficacy of ELIQUIS have not been studied in patients with prosthetic heart valves and is not recommended in these patients. Acute PE in Hemodynamically Unstable Patients or Patients who Require Thrombolysis or Pulmonary Embolectomy : Initiation of ELIQUIS is not recommended as an alternative to unfractionated heparin for the initial treatment of patients with PE who present with hemodynamic instability or who may receive thrombolysis or pulmonary embolectomy. Increased Risk of Thrombosis in Patients with Triple Positive Antiphospholipid Syndrome (APS): Direct-acting oral anticoagulants (DOACs), including ELIQUIS, are not recommended for use in patients with triple-positive APS. For patients with APS (especially those who are triple positive [positive for lupus anticoagulant, anticardiolipin, and anti–beta 2-glycoprotein I antibodies]), treatment with DOACs has been associated with increased rates of recurrent thrombotic events compared with vitamin K antagonist therapy. ADVERSE REACTIONS The most common and most serious adverse reactions reported with ELIQUIS were related to bleeding. TEMPORARY INTERRUPTION FOR SURGERY AND OTHER INTERVENTIONS ELIQUIS should be discontinued at least 48 hours prior to elective surgery or invasive procedures with a moderate or high risk of unacceptable or clinically significant bleeding. ELIQUIS should be discontinued at least 24 hours prior to elective surgery or invasive procedures with a low risk of bleeding or where the bleeding would be noncritical in location and easily controlled. Bridging anticoagulation during the 24 to 48 hours after stopping ELIQUIS and prior to the intervention is not generally required. ELIQUIS should be restarted after the surgical or other procedures as soon as adequate hemostasis has been established. DRUG INTERACTIONS Combined P-gp and Strong CYP3A4 Inhibitors: Inhibitors of P-glycoprotein (P-gp) and cytochrome P450 3A4 (CYP3A4) increase exposure to apixaban and increase the risk of bleeding. For patients receiving ELIQUIS doses of 5 mg or 10 mg twice daily, reduce the dose of ELIQUIS by 50% when ELIQUIS is coadministered with drugs that are combined P-gp and strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, or ritonavir). In patients already taking 2.5 mg twice daily, avoid coadministration of ELIQUIS with combined P-gp and strong CYP3A4 inhibitors. Clarithromycin Although clarithromycin is a combined P-gp and strong CYP3A4 inhibitor, pharmacokinetic data suggest that no dose adjustment is necessary with concomitant administration with ELIQUIS. Combined P-gp and Strong CYP3A4 Inducers: Avoid concomitant use of ELIQUIS with combined P-gp and strong CYP3A4 inducers (e.g., rifampin, carbamazepine, phenytoin, St. John’s wort) because such drugs will decrease exposure to apixaban. Anticoagulants and Antiplatelet Agents: Coadministration of antiplatelet agents, fibrinolytics, heparin, aspirin, and chronic NSAID use increases the risk of bleeding. APPRAISE-2, a placebo-controlled clinical trial of apixaban in high-risk post-acute coronary syndrome patients treated with aspirin or the combination of aspirin and clopidogrel, was terminated early due to a higher rate of bleeding with apixaban compared to placebo. PREGNANCY The limited available data on ELIQUIS use in pregnant women are insufficient to inform drug-associated risks of major birth defects, miscarriage, or adverse developmental outcomes. Treatment may increase the risk of bleeding during pregnancy and delivery, and in the fetus and neonate. Labor or delivery: ELIQUIS use during labor or delivery in women who are receiving neuraxial anesthesia may result in epidural or spinal hematomas. Consider use of a shorter acting anticoagulant as delivery approaches. LACTATION Breastfeeding is not recommended during treatment with ELIQUIS. FEMALES AND MALES OF REPRODUCTIVE POTENTIAL Females of reproductive potential requiring anticoagulation should discuss pregnancy planning with their physician. The risk of clinically significant uterine bleeding, potentially requiring gynecological surgical interventions, identified with oral anticoagulants including ELIQUIS should be assessed in these patients and those with abnormal uterine bleeding. Please see U.S. Full Prescribing Information , including Boxed WARNINGS , available at BMS.com . About the Bristol Myers Squibb-Pfizer Collaboration The Bristol Myers Squibb-Pfizer Alliance (the Alliance) is committed to driving education and awareness about atrial fibrillation and deep vein thrombosis (DVT) and/or pulmonary embolism (PE). With long-standing cardiovascular leadership, global scale and expertise in this field, the Alliance strives to implement global, research-driven approaches to illuminate and address the unmet needs around strokes related to non-valvular atrial fibrillation, which are often fatal or debilitating. Through collaborations with non-profit organizations, the Alliance aims to provide patients, healthcare professionals and decision makers with the information they need to understand and take appropriate action on risk factors associated with stroke and other cardiovascular conditions. About Bristol Myers Squibb Bristol Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol Myers Squibb, visit us at BMS.com or follow us on LinkedIn , Twitter , YouTube , Facebook and Instagram . Cautionary Statement Regarding Forward-Looking Statements This press release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995 regarding, among other things, the research, development and commercialization of pharmaceutical products. All statements that are not statements of historical facts are, or may be deemed to be, forward-looking statements. Such forward-looking statements are based on current expectations and projections about our future financial results, goals, plans and objectives and involve inherent risks, assumptions and uncertainties, including internal or external factors that could delay, divert or change any of them in the next several years, that are difficult to predict, may be beyond our control and could cause our future financial results, goals, plans and objectives to differ materially from those expressed in, or implied by, the statements. These risks, assumptions, uncertainties and other factors include, among others, that future study results may not be consistent with the results to date, that CAMZYOS (mavacamten), ELIQUIS (apixaban) or milvexian may not receive regulatory approval for the indications described in this release, any marketing approvals, if granted, may have significant limitations on their use, and, if approved whether such products and product candidates for such indications described in this release will be commercially successful. No forward-looking statement can be guaranteed. Forward-looking statements in this press release should be evaluated together with the many risks and uncertainties that affect Bristol Myers Squibb’s business and market, particularly those identified in the cautionary statement and risk factors discussion in Bristol Myers Squibb’s Annual Report on Form 10-K for the year ended December 31, 2023, as updated by our subsequent Quarterly Reports on Form 10-Q, Current Reports on Form 8-K and other filings with the Securities and Exchange Commission. The forward-looking statements included in this document are made only as of the date of this document and except as otherwise required by applicable law, Bristol Myers Squibb undertakes no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events, changed circumstances or otherwise. corporate financial-news

First and Only Pill for Children and Adolescents Ages 6-17 with Moderate to Severe Plaque Psoriasis THOUSAND OAKS, Calif., Aug. 20, 2024 /PRNewswire/ -- Amgen (NASDAQ:AMGN) today announced Otezla® (apremilast) is now available in the U.S. for pediatric use. Earlier this year, the U.S. Food and Drug Administration (FDA) approved Otezla for the treatment of moderate to severe plaque psoriasis in children and adolescents ages 6 and older who weigh at least 20 kg (44 lb) and are candidates for phototherapy or systemic therapy. There are currently no other FDA-approved oral medications for moderate to severe plaque psoriasis in this patient population. "For the first time, children and adolescents with moderate to severe plaque psoriasis and their caregivers have an oral option to treat this chronic disease, with its highly visible, uncomfortable symptoms," said Murdo Gordon, executive vice president of Global Commercial Operations at Amgen. "In the last decade, Otezla has been prescribed to over one million adults worldwide, and today's announcement represents the potential for Otezla to offer relief to many younger patients." "Children living with moderate to severe plaque psoriasis often experience uncomfortable and highly visible symptoms, such as itchy, dry lesions that may bleed or cause pain. However, treatment options for this chronic immune-mediated disease are limited," said Leah M. Howard, JD, president and CEO of the National Psoriasis Foundation. "Until now, FDA-approved systemic treatment options for youth have been injections or infusions. The addition of an oral treatment option with a well-established safety profile is great news for children with this disease and their families." The FDA approval was based on results from SPROUT, a Phase 3, multicenter, randomized, placebo-controlled, double-blind study which investigated the efficacy and safety of Otezla in pediatric patients aged 6 to 17 years with moderate to severe plaque psoriasis inadequately controlled by or intolerant to topical therapy. The primary endpoint – static Physician's Global Assessment (sPGA) response (defined as an sPGA score of clear [0] or almost clear [1] with at least a 2-point reduction from baseline) – at week 16 was met with a 33.1% sPGA response for Otezla versus 10.8% for placebo (95% CI: 12.2%, 32.4%; P<0.0001). The adverse events were consistent with the known safety profile of Otezla in adult patients. The most common side effects of Otezla include diarrhea, nausea, upper respiratory tract infection, tension headache and headache. After the initial titration period, the maintenance dosage of Otezla in this patient group will be administered in either 20 or 30 mg doses, based on weight, twice daily. The recommended dose is 20 mg twice daily for pediatric patients weighing 20 kg to <50 kg, and 30 mg twice daily for those who weigh at least 50 kg. Amgen is committed to supporting plaque psoriasis patients to ensure that appropriate patients have affordable access to Otezla. For more information, please visit Otezla.com. About Psoriasis Psoriasis is a chronic disease where skin cells build up quickly, typically causing red or discolored, scaly, and itchy patches on the skin.1 Approximately 125 million people worldwide have psoriasis, including around 14 million people in Europe and more than 8 million people in the United States.2,3 About 80% of those patients have plaque psoriasis.4 Among pediatric patients with plaque psoriasis, one in five have moderate to severe disease.5 Approximately one-third of those who get psoriasis are under 18 years old when the disease first surfaces.6 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 1 million patients worldwide.7 INDICATIONS Otezla® (apremilast) is indicated for the treatment of: Adult patients with plaque psoriasis who are candidates for phototherapy or systemic therapy Pediatric patients 6 years of age and older and weighing at least 20 kg with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy Adult patients with active psoriatic arthritis Adult patients with oral ulcers associated with Behçet's Disease 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: 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 adult 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 adult 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 adult patients treated with Otezla compared to 1% (3/382) of patients treated with placebo. Body weight loss of 5%-10% occurred in 12% (19/163) of pediatric patients with moderate to severe plaque psoriasis treated with Otezla compared to 2.5% (2/80) with placebo. Body weight loss of ≥ 10% occurred in 1% (1/163) of pediatric patients treated with Otezla twice daily compared to 0% (0/80) of patients with placebo. Closely monitor growth (height and weight) in Otezla-treated pediatric patients. Pediatric patients who are not growing or gaining weight as expected may need to have their treatment interrupted 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 adult patients with mild to moderate plaque psoriasis and pediatric patients with moderate to severe plaque psoriasis was consistent with the safety profile 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 click here for the full Prescribing Information for Otezla. 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. 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CONTACT: Amgen, Thousand Oaks Elissa Snook, 609-251-1407 (media) Kate Meyer, 872-867-0754 (media) Justin Claeys, 805-313-9775 (investors) References National Psoriasis Foundation. About Psoriasis. Available at: . Accessed June 4, 2024. National Psoriasis Foundation. Statistics. Available at: . Accessed June 4, 2024. Ortonne JP, Prinz JC. Alefacept: a novel and selective biologic agent for the treatment of chronic plaque psoriasis. Eur J Dermatol. 2004;14(1):41–45. National Psoriasis Foundation. Plaque Psoriasis. Available at: . Accessed June 4, 2024. Eichenfield LF, Paller AS, Tom WL, et al. Pediatric psoriasis. Pediatr Dermatol. 2018;35(2):170-181. Accessed June 4, 2024. Menter A, Cordoro KM, Davis DMR, et al. Joint American Academy of Dermatology-National Psoriasis Foundation guidelines of care for the management and treatment of psoriasis in pediatric patients. Available at: (19)32655-6%20/fulltext. Accessed June 4, 2024. Amgen Data on File. SOURCE Amgen