Hematoma, Epidural, Cranial

Analysis from a 10-month post-launch evaluation of the REMS Program finds 2.8% incidence of LVEF <50% in over 1500 patients, strengthening the safety pro CAMZYOS® (mavacamten) for NYHA class II-III obstructive hypertrophic cardiomyopathy Real-world data reaffirm therapeutic value and treatment benefit of CAMZYOS in improving cardiac symptoms and NYHA class in patients with obstructive hypertrophic cardiomyopathy PRINCETON, N.J.--(BUSINESS WIRE)-- Bristol Myers Squibb Company (NYSE: BMY) today announced the presentation of data at the American College of Cardiology (ACC) Annual Scientific Session & Expo, taking place April 6-8, 2024 in Atlanta, Georgia. “The therapeutic benefit of CAMZYOS in real-world practice, demonstrated by our data at ACC, builds on the well-established clinical program and further underscores the importance of this transformational medicine which is the first and only approved cardiac myosin inhibitor. With thousands of patients around the world treated to date, CAMZYOS is redefining the treatment landscape for this patient population and may offer hope to countless others moving forward,” said Roland Chen, MD, Senior Vice President and Head of Development, Immunology, Cardiovascular & Neurology. “In addition to showcasing our growing body of real-world evidence and safety data for CAMZYOS at ACC, we look forward to highlighting additional data from our cardiovascular portfolio, including an analysis of the real-world clinical impact of ELIQUIS.” Research to be presented at the meeting supports the robust safety and clinical pro CAMZYOS® (mavacamten) and compliance with the Risk Evaluation and Mitigation Strategy (REMS) Program. These data include: An analysis of results from the 10-month post-launch evaluation of the CAMZYOS REMS Program in 1,524 patients with patient status forms submitted, which demonstrated that approximately 1% (n=17) of patients reported clinical heart failure requiring hospitalization and 2.8% (n=43) of patients reported a decrease in left ventricular ejection fraction (LVEF) to <50%. These data are consistent with the clinical development program and reinforce the safety pro CAMZYOS in clinical practice. These data (abstract 1075-07) will be featured as a moderated poster on Sunday, April 7 from 1:30 PM – 1:40 PM ET. A single-center real-world experience analysis of 53 patients treated with CAMZYOS which found that at 24 weeks, CAMZYOS led to improvements in cardiovascular symptoms (96%) and improvements in one or more New York Heart Association (NYHA) class (49%). Additionally, resting and Valsalva LVOT gradient decreased during the first four weeks after starting treatment, with statistically significant reductions from baseline at week 24 (P<0.001). No patients required cessation of treatment due to reduction of LVEF to <50% or other side effects, though two patients required temporary drug discontinuation due to Valsalva LVOT gradient less than 20 mmHg during the 24-week treatment period. These data (abstract 1424-134) will be featured as a poster on Sunday, April 7 from 1:15 PM – 2:00 PM ET. The BMS-Pfizer Alliance will also present research at the meeting that adds to the robust body of evidence pertaining to the safety and efficacy pro ELIQUIS® (apixaban). These data include: A real-world evidence study of non-valvular atrial fibrillation (NVAF) patients on Medicare previously treated with warfarin and switched to a direct oral anticoagulant (DOAC: apixaban, dabigatran, or rivaroxaban), which found that those who received ELIQUIS had a statistically significant lower risk of stroke/systemic embolism (S/SE) and major bleeding (MB) than those patients who received rivaroxaban (S/SE HR: 0.91; 95% CI: 0.85-0.97 and MB HR: 0.68; 95% CI: 0.65-0.72) or dabigatran (S/SE HR: 0.83; 95% CI: 0.72-0.96 and MB HR: 0.79; 95% CI: 0.71-0.89). This pairwise comparative analysis provides the rates of S/SE and MB shown in patients with NVAF on Medicare associated with switching from warfarin to different DOACs. This effectiveness and safety information about ELIQUIS use in clinical practice can supplement data from randomized clinical trials. These data (abstract 1306-157) will be featured as a poster on Saturday, April 6 from 2:45 PM – 3:00 PM ET. Select BMS and BMS-Pfizer Alliance-sponsored abstracts to be presented at ACC 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 Time (ET) Saturday, April 6, 2024 The experiences, values and goals of people in Australia living with obstructive hypertrophic cardiomyopathy: In-depth patient interviews Fifer, S. Poster – 1244-128 1244 - Heart Failure and Cardiomyopathies: Basic and Translational Science 03 11:45 AM – 12:30 PM Effect of mavacamten on health status in Chinese patients with symptomatic obstructive hypertrophic cardiomyopathy: Results from the EXPLORER-CN study Tian, Z. Poster – 1284-132 1284 - Heart Failure and Cardiomyopathies: Pharmacology 05 1:45 PM – 2:30 PM Evaluation of effectiveness and safety outcomes among Medicare patients with non-valvular atrial fibrillation who switched from warfarin to direct oral anticoagulants* Atreja, N. Poster – 1306-157 1306 - Ischemic Heart Disease: Special Populations 06 2:45 PM – 3:30 PM Sunday, April 7, 2024 Greatest absolute benefit of apixaban and limiting aspirin is in those with comorbidity: Results from the AUGUSTUS trial* Krychtiuk, K. Poster – 1065-11 1065 - Vascular Vistas: Tailored Research for Special Populations 12:00 PM – 12:10 PM Real-world experience and 24-week outcomes of patients with symptomatic obstructive hypertrophic cardiomyopathy treated with mavacamten in the US Reza, N. Poster – 1424-134 1424 - Heart Failure and Cardiomyopathies: Special Populations 12 1:15 PM – 2:00 PM The CAMZYOS (mavacamten) risk evaluation and mitigation strategy program: Results from 10 months post-launch Martinez, M. Poster – 1075-07 1075 - Bulking Up: Advances in Hypertrophic Cardiomyopathy 1:30 PM – 1:40 PM Effects of mavacamten on circulating biomarkers in obstructive hypertrophic cardiomyopathy: Insights from the EXPLORER-HCM study using comprehensive proteomics profiling Wang, Z. Poster – 1075-09 1075 - Bulking Up: Advances in Hypertrophic Cardiomyopathy 1:45 PM – 1:55 PM *Sponsored by the Bristol Myers Squibb-Pfizer Alliance 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 (HCM) 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 on five continents including in Argentina, Australia, Brazil, Canada, Great Britain, Hong Kong, Israel, Singapore, South Korea, and Switzerland. 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 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. CAMZYOS may reduce the effectiveness of combined hormonal contraceptives (CHCs). Advise patients using CHCs to use an alternative contraceptive method that is not affected by CYP 450 enzyme induction or to add nonhormonal contraception. Advise females of reproductive potential about the potential risk to the fetus with maternal exposure to CAMZYOS during pregnancy. 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 where decreases in the plasma concentration of these drugs may reduce their activity. Hormonal Contraceptives: Progestin and ethinyl estradiol are CYP3A4 substrates. Concomitant use of CAMZYOS may decrease exposures of ethinyl estradiol and progestin, which may lead to contraceptive failure or an increase in breakthrough bleeding. Advise patients to use a contraceptive method that is not affected by CYP 450 enzyme induction (e.g., intrauterine system) or 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 . 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. Use of CAMZYOS may reduce the effectiveness of CHCs. Advise patients using CHCs to use an alternative contraceptive method or add nonhormonal contraception. 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 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 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. 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. 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 the results of future post-marketing studies will be consistent with the results of these studies, that CAMZYOS (mavacamten) or ELIQUIS (apixaban) may not be commercially successful, any marketing approvals, if granted, may have significant limitations on their use, and that continued approval of such products for such indications may be contingent upon verification and description of clinical benefit in additional confirmatory trials. 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. corporatefinancial-news

New clinical analyses and real-world data continue to demonstrate the benefit of treatment with CAMZYOS® (mavacamten) for patients with symptomatic obstructive HCM PRINCETON, N.J.--(BUSINESS WIRE)-- Bristol Myers Squibb (NYSE: BMY) today announced that research across the company’s cardiovascular franchise will be presented at the American Heart Association’s (AHA) annual Scientific Sessions, taking place November 11-13, 2023 in Philadelphia, Pennsylvania. Clinical trial data to be featured include new analyses of the effectiveness of CAMZYOS® (mavacamten) in patients with and without gene variants from the Phase 3 EXPLORER-HCM study, as well as new real-world analyses of patients with symptomatic New York Heart Association (NYHA) class II-III obstructive hypertrophic cardiomyopathy (HCM) receiving CAMZYOS in clinical practice. The Bristol Myers Squibb-Pfizer Alliance will also provide new data describing disparity in oral anticoagulant utilization patterns among commercially insured patients with non-valvular atrial fibrillation (NVAF) with high stroke risk by geographic region and race in the U.S. “We’re looking forward to the opportunity to showcase new clinical and real-world analyses across our cardiovascular franchise, which support our commitment to develop medicines that address the global burden of cardiovascular disease,” said Roland Chen, Senior Vice President, Head of Development, Immunology, Cardiovascular & Neurology. “These data at the AHA Scientific Sessions continue to demonstrate the benefit that treatment with CAMZYOS provides for a broad spectrum of patients with symptomatic obstructive hypertrophic cardiomyopathy in clinical studies as well as in clinical practice.” Key presentations include: An exploratory subgroup analysis of the Phase 3 EXPLORER-HCM study analyzing treatment effectiveness with CAMZYOS for patients with and without sarcomere gene variants. Findings from an analysis of an EXPLORER-HCM study assessing the relationship between patient-reported KCCQ and physician-assessed NYHA class to enhance understanding of KCCQ scores and aid shared decision-making process of patients and physicians in clinical practice. A retrospective cohort study of claims data from commercial specialty pharmacies demonstrating high real-world adherence to CAMZYOS in >600 patients with symptomatic obstructive HCM in the United States. An analysis of Medicare claims data from 2016 to 2020 investigating evidence of diagnosis-related disparities in patients over 65 with HCM specifically relating to race/ethnicity and county-level disparities. Summary of Presentations Select Bristol Myers Squibb and Bristol Myers Squibb-Pfizer Alliance studies at AHA Congress 2023 include: Abstract Title Primary Author Type/# Session Title Time (EST) Saturday, November 11, 2023 Real-World Adherence to Mavacamten in Patients With Obstructive Hypertrophic Cardiomyopathy in the United States Masri, A. Poster – 3002 Drugs, Drugs, and More Drugs: New Pharmacologic Insights in Heart Failure Management 11:30 AM – 12:45 PM Disparities in Speed of Diagnosis of Hypertrophic Cardiomyopathy in the United States Masri, A. Rapid Oral Fire – 515 Exciting Developments in Heart Failure Diagnosis and Evaluation 12:10 PM – 12:15 PM Healthcare Resource Utilization and Costs Associated With New York Heart Association Functional Class in Patients With Obstructive Hypertrophic Cardiomyopathy in the United States Wang, Y. Poster – 3116 Socioeconomic Disparities and Cardiovascular Health 3:00 PM – 4:15 PM Biomarker Pro Patients With Atrial Fibrillation and Heart Failure With Preserved Ejection Fraction or Reduced Ejection Fraction: Insights From the ARISTOTLE Trial* Pol, T. Poster - 1059 HFpEF 3:00 PM – 4:15 PM Sunday, November 12, 2023 Real-World Patients With Obstructive Hypertrophic Cardiomyopathy Treated With Mavacamten: A US Single Center Experience Reza, N. Poster – 2160 Hypertrophic, Obstructive, and Takotsubo Cardiomyopathy: From Genetics to Outcomes 11:30 AM – 12:45 PM Monday, November 13, 2023 Relationship Between the Kansas City Cardiomyopathy Questionnaire Score and New York Heart Association Class in Patients With Hypertrophic Cardiomyopathy: Insights from EXPLORER-HCM Sherrod, C. Poster - 2194 Game Changing Disease Management in Hypertrophic, Amyloid, and Cardiomyopathy Care 10:30 AM –11:45 AM Geographic and Racial Variation in Oral Anticoagulant Treatment Among Commercially Insured Patients With Non-Valvular Atrial Fibrillation in the United States* Atwater, B. E-poster - 2146 Treatment of Arrhythmias: Risk Stratification for Stroke and Stroke Reduction Therapies 1:30 PM – 2:45 PM Response to Mavacamten by Sarcomere Gene Mutation Status in EXPLORER-HCM Ho, C. Rapid fire oral – 551 The Pharmacologic Management of Heart Failure: Beyond Guidelines and Paradigms 1:50 PM – 1:55 PM The Effect of Mavacamten Treatment on Hemolysis Biomarkers in Patients With Obstructive Hypertrophic Cardiomyopathy in the EXPLORER-HCM Study Wang, Z. Rapid fire oral – 553 The Pharmacologic Management of Heart Failure: Beyond Guidelines and Paradigms 2:10 PM – 2:15 PM *Sponsored by the Bristol Myers Squibb-Pfizer Alliance 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 (HCM) 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 on five continents including in Argentina, Australia, Brazil, Canada, Great Britain, Israel, Macau, Singapore, South Korea, and Switzerland. 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 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. CAMZYOS may reduce the effectiveness of combined hormonal contraceptives (CHCs). Advise patients using CHCs to use an alternative contraceptive method that is not affected by CYP 450 enzyme induction or to add nonhormonal contraception. Advise females of reproductive potential about the potential risk to the fetus with maternal exposure to CAMZYOS during pregnancy. 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 where decreases in the plasma concentration of these drugs may reduce their activity. Hormonal Contraceptives: Progestin and ethinyl estradiol are CYP3A4 substrates. Concomitant use of CAMZYOS may decrease exposures of ethinyl estradiol and progestin, which may lead to contraceptive failure or an increase in breakthrough bleeding. Advise patients to use a contraceptive method that is not affected by CYP 450 enzyme induction (e.g., intrauterine system) or 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 . 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. Use of CAMZYOS may reduce the effectiveness of CHCs. Advise patients using CHCs to use an alternative contraceptive method or add nonhormonal contraception. 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 PRECAUTION 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 for more information on availability of a 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 . 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. 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. 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 the product candidates may not receive regulatory approval for the indications described in this release, that future study results may not be consistent with the results to date, that any marketing approvals, if granted, may have significant limitations on their use, and, if approved, whether such 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, 2022, 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. corporatefinancial-news

Switching from Eliquis (apixaban) to rivaroxaban in Non-Valvular Atrial Fibrillation (NVAF) patients was associated with a higher risk of stroke/systemic embolism (S/SE) and major bleeding (MB) than those who continued Eliquis PRINCETON, N.J. & NEW YORK--(BUSINESS WIRE)-- The Bristol Myers Squibb-Pfizer (BMS NYSE: BMY) – (Pfizer NYSE: PFE) Alliance today presented results from ATHENS, a retrospective real-world data study, at the European Society of Cardiology (ESC) Congress 2023 showing that switching from Eliquis® (apixaban) to rivaroxaban in Non-Valvular Atrial Fibrillation (NVAF) patients was associated with a higher risk of stroke/systemic embolism (S/SE) and major bleeding (MB) than those who continued Eliquis. “Although some NVAF patients switch direct oral anticoagulants in real-world clinical practice, either for medical or non-medical reasons, there hasn’t been a lot of information gathered on the clinical outcomes of those switches,” said Steve Deitelzweig, MD, MMM, FACC, SFHM, FACP, RVT, System Chairman for Hospital Medicine, Ochsner Health System. “The study results provide insights about the real-world risk of stroke and major bleeding associated with switching from apixaban to rivaroxaban in patients with NVAF.” This retrospective study identified NVAF patients who initiated Eliquis or rivaroxaban between 01 January 2013 and 31 December 2021 using Optum’s de-identified Clinformatics® Data Mart database. There were 167,868 Eliquis initiators and 65,888 rivaroxaban initiators who met study criteria. Using propensity score matching (PSM), 2,900 patients who switched from Eliquis to rivaroxaban were matched to 14,500 patients who continued Eliquis, and 2,873 patients who switched from rivaroxaban to Eliquis were matched to 14,365 patients who continued rivaroxaban. "Data collected in real-world settings can enhance patient care. By gathering insights from everyday clinical practice, we can better understand how Eliquis is used and its impact on patients’ lives,” said Narinder Bhalla, MD, Senior Vice President, Worldwide Medical, Head of Cardiovascular and Established Brands at Bristol Myers Squibb. “This real-world data provides pragmatic information to help clinicians manage the care of their patients.” In this study, switching from Eliquis to rivaroxaban was associated with a higher risk of S/SE (Hazard Ratio (HR):1.99, 95% Confidence Interval (CI): 1.38-2.88) and MB (HR: 1.80, 95% CI: 1.46-2.23) than those who continued Eliquis. Additionally, switching from rivaroxaban to Eliquis was associated with a similar risk of S/SE (HR:0.74, 95% CI: 0.45-1.22) and a lower risk of MB (HR:0.58, 95%CI: 0.44-0.76) compared to those who continued rivaroxaban. It is important to note that anticoagulants, including Eliquis, increase the risk of bleeding and can cause serious, potentially fatal bleeding. Please see important safety information below for Eliquis, including BOXED WARNINGS. Real-world data have the potential to supplement randomized, controlled clinical trial data by providing additional information about how a medicine performs in routine medical practice. Real-world data analyses, however, have important limitations. Observational real-world studies can only evaluate association and not causality, and despite the use of methods to address differences due to measured variables, false associations may still be present. The source and type of data used may limit the generalizability of the results, and varied outcomes are possible. In the ATHENS study, treatment assignments were based on pharmacy claims and actual drug exposure is unknown. Additionally, reasons for switching are not known and sample size for those who switched is much lower than those who continued treatment. Dosing criteria were not evaluated and impacts of drug dosing on outcomes were not assessed. Due to these limitations, real-world data analyses are not used as evidence to validate the efficacy and/or safety of a treatment. About ATHENS The ATHENS study was designed to assess the risk of stroke/systemic embolism (S/SE) and major bleeding (MB) among Non-Valvular Atrial Fibrillation (NVAF) patients who switched from Eliquis (apixaban) to rivaroxaban or switched from rivaroxaban to Eliquis instead of continuing initial treatment. This retrospective study identified NVAF patients who initiated treatment between 01 January 2013 and 31 December 2021 using a large U.S. administrative claims database. There were 167,868 Eliquis initiators and 65,888 rivaroxaban initiators included in the study. Within both the Eliquis initiators and rivaroxaban initiators cohorts, patients were divided into two groups and compared: switchers to a different direct oral anticoagulant (DOAC) within 30 days before or 90 days after discontinuation of the initial DOAC, and continuers, or patients who continued receiving the initial DOAC. The switch date was the index date for those who switched while, for those who continued, a hypothetic index date was randomly assigned based on the distribution of the time from initial DOAC prescription to the switch date in the switchers group. Two final cohorts (switchers and continuers) within Eliquis initiators and rivaroxaban initiators were further propensity score matched (PSM) based on pre-index characteristics using a 1:5 ratio. 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. The approval of Eliquis for stroke risk reduction in patients with NVAF is based on data from the Phase 3 ARISTOTLE and AVERROES studies of Eliquis in patients with NVAF. The approval of Eliquis for the treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), and for the reduction in the risk of recurrent DVT and PE following initial therapy, is based on data from the global AMPLIFY and AMPLIFY-EXT studies. U.S. FDA-Approved Indications for Eliquis: Eliquis is a prescription medicine indicated in the U.S. to reduce the risk of stroke and systemic embolism in patients with 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 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 PRECAUTION 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 for more information on availability of a 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 . 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. About Pfizer Inc.: Breakthroughs That Change Patients’ Lives At Pfizer, we apply science and our global resources to bring therapies to people that extend and significantly improve their lives. We strive to set the standard for quality, safety and value in the discovery, development and manufacture of health care products, including innovative medicines and vaccines. Every day, Pfizer colleagues work across developed and emerging markets to advance wellness, prevention, treatments and cures that challenge the most feared diseases of our time. Consistent with our responsibility as one of the world's premier innovative biopharmaceutical companies, we collaborate with health care providers, governments and local communities to support and expand access to reliable, affordable health care around the world. For more than 170 years, we have worked to make a difference for all who rely on us. We routinely post information that may be important to investors on our website at In addition, to learn more, please visit us on and follow us on Twitter at @Pfizer and @Pfizer News, LinkedIn, YouTube and like us on Facebook at Facebook.com/Pfizer. Bristol Myers Squibb 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. 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, 2022, 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. Pfizer Disclosure Notice The information contained in this release is as of August 25, 2023. Pfizer assumes no obligation to update forward-looking statements contained in this release as the result of new information or future events or developments. This release contains forward-looking information about Eliquis (apixaban), including its potential benefits, that involves substantial risks and uncertainties that could cause actual results to differ materially from those expressed or implied by such statements. Risks and uncertainties include, among other things, the uncertainties inherent in research and development, including the ability to meet anticipated clinical endpoints, commencement and/or completion dates for our clinical trials, regulatory submission dates, regulatory approval dates and/or launch dates, as well as the possibility of unfavorable new clinical or other data and further analyses of existing clinical or other data; the risk that clinical trial data are subject to differing interpretations and assessments by regulatory authorities; whether regulatory authorities will be satisfied with the design of and results from our clinical studies; decisions by regulatory authorities impacting labeling, manufacturing processes, safety and/or other matters that could affect the availability or commercial potential of Eliquis; uncertainties regarding commercial success; uncertainties regarding the impact of COVID-19 on Pfizer’s business, operations and financial results; and competitive developments. A further description of risks and uncertainties can be found in Pfizer’s Annual Report on Form 10-K for the fiscal year ended December 31, 2022 and in its subsequent reports on Form 10-Q, including in the sections thereof captioned “Risk Factors” and “Forward-Looking Information and Factors That May Affect Future Results,” as well as in its subsequent reports on Form 8-K, all of which are filed with the U.S. Securities and Exchange Commission and available at and . corporatefinancial-news