Bristol Myers Squibb Announces Data from EXPLORER-LTE Demonstrating Sustained Improvements in Clinically Meaningful Cardiovascular Outcomes at Weeks 48 and 84 in Patients with Symptomatic Obstructive Hypertrophic Cardiomyopathy Receiving Mavacamten

Treatment with mavacamten showed sustained improvement in left ventricular outflow tract (LVOT) gradients, New York Heart Association (NYHA) Class and N-terminal pro brain natriuretic peptide (NT-proBNP) levels

At 48 and 84 Weeks, Mavacamten safety was consistent with that seen in the EXPLORER-HCM study

Interim results were presented as a late-breaking clinical trial at the American College of Cardiology’s 71^st Annual Scientific Session

PRINCETON, N.J.--(BUSINESS WIRE)--$BMY #ACC--Bristol Myers Squibb (NYSE: BMY) today announced new, interim results from the EXPLORER-LTE cohort of the MAVA-LTE study (NCT03723655), the largest and longest evaluation of mavacamten, an investigational, first-in-class cardiac myosin inhibitor, in patients with symptomatic obstructive hypertrophic cardiomyopathy (obstructive HCM). These data, which showed sustained improvements in cardiovascular outcomes at 48 and 84 weeks, were presented today as a late-breaking clinical trial at the American College of Cardiology’s 71^st Annual Scientific Session.

EXPLORER-LTE enrolled 231 of the 244 patients who were eligible for the long-term extension study at the end of the Phase 3 parent trial, EXPLORER-HCM (NCT03470545). Over 200 patients remained on study for more than 48 weeks, and 67 patients had reached 84 weeks. Clinically meaningful improvements were sustained in left ventricular outflow tract (LVOT) gradients, New York Heart Association (NYHA) Class and N-terminal pro brain natriuretic peptide (NT-proBNP) levels at 48 weeks and up to 84 weeks. The safety profile remained consistent with EXPLORER-HCM. No new safety signals were observed during longer term follow-up and the exposure adjusted event rates were stable or lower in this cohort.

“These data underscore the potential of mavacamten to offer rapid and sustained improvement in key cardiac measures in patients living with this chronic, and sometimes progressive, disease,” said Florian Rader, M.D., M.Sc. co-director of the Clinic for Hypertrophic Cardiomyopathy, Cedars-Sinai Medical Center.

EXPLORER-LTE is a cohort of the MAVA-LTE study, an ongoing, dose-blinded, 5-year study of mavacamten in patients with symptomatic obstructive HCM who completed the EXPLORER-HCM trial. EXPLORER-HCM enrolled a total of 251 adult patients with NYHA Class II or III obstructive HCM. All participants had measurable left ventricular ejection fraction (LVEF) ≥55% and LVOT gradient (resting and/or provoked) ≥50 mmHg at baseline. Patients were randomized in a 1:1 ratio to receive either a starting dose of 5 mg of mavacamten or placebo once daily for 30 weeks.

All participants in the EXPLORER-LTE cohort started on 5 mg of mavacamten daily and dose adjustments were made at Weeks 4, 8 and 12 based on site-read echocardiography measures of Valsalva LVOT gradient and LVEF only. Dose adjustment was also possible at Week 24 following site-read echocardiography assessment of post-exercise LVOT gradient. Temporary discontinuation criteria included LVEF <50%, mavacamten plasma trough concentration ≥1000 ng/mL or increase in corrected QT interval by Fredericia (QTcF) >15%. Current efficacy and safety data are representations of interim data from April 2019 through August 2021 in the ongoing MAVA-LTE study. As of the August 2021 interim analysis cutoff date, 94% of patients remained on mavacamten.

Findings included:

• Resting LVOT gradient decreased from baseline by an average of -35.6 mmHg ± 32.6 mmHg at Week 48. Similar reductions persisted throughout this extension period (up to 84 weeks).
• Similarly, Valsalva LVOT gradient decreased from baseline by an average of -45.3 mmHg ± 35.9 mmHg at Week 48. Sustained efficacy persisted throughout this extension period (up to 84 weeks).
• Serum NT-proBNP levels decreased from baseline by a median of -480 ng/L (IQR: −1104 ng/L, −179 ng/L) at Week 48. Similar reductions persisted throughout this extension period (up to 84 weeks).
• At Week 48, 67.5% (139/206) of patients improved by ≥1 NYHA Class from baseline, with 60.2% (124/206) improving by 1 NYHA Class and 7.3% (15/206) improving by 2 NYHA Classes. Improvements in NYHA Class were first observed at Week 12 and showed sustained improvement through Week 48.
• Resting LVEF decreased from baseline by -7.0% ± 8.3% at Week 48. Similar level of reduction persisted throughout this extension period (up to 84 weeks).
• Safety data showed 10 (4.3%) study participants permanently discontinuing due to treatment-emergent adverse events (TEAEs) and 26 (11%) discontinuing temporarily for any reason and resuming treatment thereafter. Of these, 12 (5.2%) patients had LVEF <50%, 2 of which were considered TEAEs, and all recovered LVEF >50% without further side effects.

“Interim results from this EXPLORER-LTE cohort build upon the clinical evidence supporting the potential for longer-term use of mavacamten in patients with symptomatic obstructive HCM,” said Marie-Laure Papi, vice president and mavacamten development program lead, Bristol Myers Squibb. “We look forward to the opportunity to bring this medicine to patients and eagerly await the U.S. Food and Drug Administration’s decision on our New Drug Application later this month.”

About Obstructive Hypertrophic Cardiomyopathy

Obstructive hypertrophic cardiomyopathy (obstructive HCM) is a chronic, progressive disease in which excessive contraction of the heart muscle and reduced ability of the left ventricle to fill can make it difficult for blood to circulate to the rest of the body, leading to the development of debilitating symptoms and cardiac dysfunction. HCM can be hereditary and can develop at any age. Patients are typically diagnosed in their 40s or 50s, and as many as 50% of patients have a hereditary predisposition.

In obstructive HCM, which is the most common type of HCM, the left ventricular outflow tract (LVOT) where blood leaves the heart becomes obstructed by the enlarged heart muscle. As a result, obstructive HCM has also been associated with increased risks of atrial fibrillation, stroke, heart failure and, although rare, sudden cardiac death. The most frequent cause of obstructive HCM is mutations in the heart muscle proteins of the sarcomere. It is estimated that approximately 400,000-600,000 people are diagnosed with obstructive HCM worldwide, and a significant number of additional people remain undiagnosed and/or asymptomatic.

About Mavacamten

Mavacamten is a first-in-class, oral, allosteric modulator of cardiac myosin being investigated for the treatment of symptomatic obstructive hypertrophic cardiomyopathy (obstructive HCM) which is a progressive disease that thickens the heart walls and makes it harder for the heart to expand normally and fill with blood. It is a selective cardiac myosin inhibitor that targets the underlying pathophysiology of obstructive HCM.

Mavacamten has been shown to reduce cardiac muscle contractility by inhibiting excessive myosin-actin cross-bridge formation that results in hypercontractility, left ventricular hypertrophy and reduced compliance. Based on data from the EXPLORER-HCM study, the company has a PDUFA date in the U.S. of April 28, 2022.

In clinical and preclinical studies, mavacamten has consistently reduced biomarkers of cardiac wall stress, lessened excessive cardiac contractility, increased diastolic compliance and lessened left ventricular outflow tract (LVOT) gradients.

Mavacamten is an investigational therapy and is not approved for use in any country.

About Bristol Myers Squibb

Bristol Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol Myers Squibb, visit us at BMS.com or follow us on LinkedIn, Twitter, YouTube, Facebook and Instagram.

Cautionary Statement Regarding Forward-Looking Statements

This press release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995 regarding, among other things, the research, development and commercialization of pharmaceutical products. All statements that are not statements of historical facts are, or may be deemed to be, forward-looking statements. Such forward-looking statements are based on current expectations and projections about our future financial results, goals, plans and objectives and involve inherent risks, assumptions and uncertainties, including internal or external factors that could delay, divert or change any of them in the next several years, that are difficult to predict, may be beyond our control and could cause our future financial results, goals, plans and objectives to differ materially from those expressed in, or implied by, the statements. These risks, assumptions, uncertainties and other factors include, among others, that future study results will be consistent with the results to date, that mavacamten may not receive regulatory approval for the indication described in this release in the currently anticipated timeline or at all, any marketing approvals, if granted, may have significant limitations on their use, and, if approved, whether such product candidate for such indication 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, 2021, 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.

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