New analyses, including late-breaking data and presentations on CAMZYOS® (mavacamten) and Eliquis® (apixaban), reaffirm the company’s steadfast dedication to tackling cardiovascular diseases
PRINCETON, N.J.–(BUSINESS WIRE)–$BMY #AFib—Bristol Myers Squibb (NYSE: BMY) today announced the presentation of research reinforcing the strength of its robust cardiovascular portfolio at the European Society of Cardiology (ESC) Congress, taking place in-person and virtually August 25-28, 2023. Data from clinical studies will be featured, including presentations of CAMZYOS® (mavacamten) cumulative analysis up to 120-weeks and impact to standard of care (SOC) medication from the EXPLORER cohort of the MAVA-long-term extension (LTE) study, as well as a late-breaking presentation of VALOR-HCM-LTE 56-week data, and new data from health economics outcomes research. The Bristol Myers Squibb-Pfizer Alliance will also share an observational retrospective real-world study on the clinical impact of switching or continuation of Eliquis® (apixaban) or rivaroxaban among patients with non-valvular atrial fibrillation (NVAF).
“This year’s ESC Congress provides the opportunity to present new data spanning our cardiovascular portfolio, reinforcing our ambition of bringing innovative and life-changing medicines to patients living with cardiovascular diseases,” said Roland Chen, MD, Senior Vice President and Head of Cardiovascular & Neuroscience Development, Global Drug Development. “These data demonstrate the consistency and impact of our cardiovascular medicines – ranging from treatments that have been available to patients with atrial fibrillation for over a decade to our more recent therapeutic option tackling symptomatic obstructive hypertrophic cardiomyopathy.”
Key presentations include:
- A late-breaking oral presentation of data from the 56-week VALOR-HCM-LTE study evaluating CAMZYOS in severely symptomatic obstructive hypertrophic cardiomyopathy patients eligible for septal reduction therapy (SRT).
- An updated cumulative analysis of the EXPLORER cohort of the MAVA-LTE study analyzing treatment with CAMZYOS for up to 120 weeks.
- An exploratory analysis from the EXPLORER cohort of MAVA-LTE investigating the effect of changes in SOC medication on the efficacy and safety of CAMZYOS.
- An observational retrospective real-world data study of the clinical impact of switching or continuation of initial Eliquis or rivaroxaban treatment on the risk of stroke/systemic embolism and major bleeding in patients with NVAF.
Summary of Presentations
Select Bristol Myers Squibb and Bristol Myers Squibb-Pfizer Alliance studies at ESC Congress 2023 include:
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Abstract Title |
Primary |
Type/# |
Session Title |
Time |
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Friday, August 25, 2023 |
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Multiplex screening for biomarkers associated with subsequent heart failure hospitalisation in patients with atrial fibrillation: insights from the ARISTOTLE trial* |
Pol, T. |
Moderated Poster – 3096 |
Pathophysiology and Mechanisms |
8:15 AM – |
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Repeated measurement of the novel atrial biomarker BMP10 improves risk stratification in anticoagulated patients with atrial fibrillation: insights from the ARISTOTLE trial* |
Gkarmiris, KI. |
Moderated e-Poster – 811 |
Advances in Science |
8:30 AM – |
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Clinical impact of switching or continuation of apixaban or rivaroxaban among patients with non-valvular atrial fibrillation: insights from the observational retrospective real-world data study* |
Deitelzweig, S. |
Moderated e-Poster – 3346 |
Oral anticoagulation in patients with atrial fibrillation |
4:15 PM – |
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Sunday, August 27, 2023 |
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Long-term effects of mavacamten treatment in obstructive hypertrophic cardiomyopathy (HCM): updated cumulative analysis of the EXPLORER cohort of MAVA-long-term extension (LTE) study up to 120 weeks |
Garcia-Pavia, P. |
Oral – 83538 | Contemporary management of hypertrophic cardiomyopathy |
10:15 AM – |
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Changes in standard of care (SOC) medication during long-term mavacamten treatment for obstructive hypertrophic cardiomyopathy (HCM): results from the EXPLORER cohort of MAVA-Long-Term Extension (LTE) |
Lakdawala, N. |
Moderated Poster – 83579 | Cardiomyopathies in myocardial disease |
5:15 PM – |
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Association between hospital volume, clinical events, resource utilization, and costs of septal myectomy and alcohol septal ablation procedures in US patients with hypertrophic cardiomyopathy |
Maksabedian Hernandez, E.J. |
Moderated-Poster – 86138 | Cardiomyopathies in myocardial disease |
5:15 PM – |
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Monday, August 28, 2023 |
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EXPLORER-CN – Efficacy and safety of mavacamten in Chinese adults with symptomatic obstructive hypertrophic cardiomyopathy** |
Tian, Z. |
Oral |
Late-breaking science on valve disease and hypertrophic cardiomyopathy |
5:00 PM – |
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VALOR-HCM 56 Week Long-term Extension Study in oHCM |
Desai, M. |
Oral |
Late-breaking science on valve disease and hypertrophic cardiomyopathy |
5:15 PM – |
*Sponsored by the Bristol Myers Squibb-Pfizer Alliance
**Sponsored by LianBio
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 in Australia, Brazil, Canada, Great Britain, 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 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. 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 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. 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.
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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 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 affectinghemostasis. Indwelling epidural or intrathecal catheters should not be removed earlier than 24 hours after the last administration of ELIQUIS. The next doseof ELIQUIS should not be administered earlier than 5 hours after the removal of the catheter. The risk may also be increased by traumatic or repeatedepidural 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.
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