PRINCETON, NJ–(BUSINESS WIRE)–April 3, 2022–
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 the myosin inhibitor mavacamten experimental, first-in-class cardiac therapy 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 71st Annual Scientific Session. .
EXPLORER-LTE enrolled 231 of 244 patients eligible for the long-term extension study at the end of the parent Phase 3 trial, EXPLORER-HCM (NCT03470545). More than 200 patients remained on study for more than 48 weeks and 67 patients had reached 84 weeks. Clinically meaningful improvements were maintained in left ventricular outflow tract (LVOT) gradients, New York Heart Association (NYHA) class, and N-terminal procerebral 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 exposure-adjusted event rates were stable or lower in this cohort.
“These data underscore the potential of mavacamten to provide rapid and sustained improvement in key cardiac measures in patients living with this chronic and sometimes progressive disease,” said Florian Rader, MD, M.Sc. 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 recruited a total of 251 adult patients with obstructive NYHA class II or III HCM. All participants had a measurable left ventricular ejection fraction (LVEF) ≥ 55% and an LVOT gradient (resting and/or provoked) ≥ 50 mmHg at baseline. Patients were randomized 1:1 to receive either a starting dose of 5 mg mavacamten or placebo once daily for 30 weeks.
All participants in the EXPLORER-LTE cohort were started on 5 mg mavacamten daily and dose adjustments were made at weeks 4, 8, and 12 based on site-read echocardiography measurements of the Valsalva LVOT gradient and LVEF only. Dose adjustment was also possible at week 24 after on-site echocardiographic assessment of the post-exercise LVOT gradient. Temporary discontinuation criteria included LVEF 15%. The 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 deadline, 94% of patients remained on mavacamten.
- The 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, the Valsalva LVOT gradient decreased from baseline by a mean of -45.3 mmHg ± 35.9 mmHg at week 48. Sustained efficacy persisted throughout this extension period (until at 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. throughout this extended 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) an improvement of 2 NYHA classes. NYHA class improvements 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. A similar level of reduction persisted throughout this extension period (up to 84 weeks).
- Safety data showed that 10 (4.3%) study participants permanently discontinued due to treatment-related adverse events (TEAEs) and 26 (11%) temporarily discontinued for any reason and subsequently resumed treatment. Of these, 12 (5.2%) patients had LVEF 50% no other side effects.
“The interim results of this EXPLORER-LTE cohort build on 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 Manager, Bristol Myers Squibb. “We look forward to the opportunity to bring this drug to patients and look forward to the U.S. Food and Drug Administration’s decision on our New Drug Application later this month.”
About Hypertrophic Obstructive 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 flow to the rest of the body, leading to the development of symptoms debilitating and cardiac dysfunction. HCM can run in families and can develop at any age. Patients are usually diagnosed in their 40s or 50s, and up to 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 is blocked by 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 common cause of obstructive HCM is mutation of heart muscle sarcomere proteins. It is estimated that approximately 400,000 to 600,000 people are diagnosed with obstructive HCM worldwide, with a significant number of additional people remaining undiagnosed and/or asymptomatic.
Mavacamten is a first-in-class oral allosteric modulator of cardiac myosin being studied for the treatment of symptomatic obstructive hypertrophic cardiomyopathy (obstructive HCM) which is a progressive disease that thickens the walls of the heart and makes it more difficult 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 the excessive formation of myosin-actin cross-bridges which results in hypercontractility, left ventricular hypertrophy and reduced compliance. Based on data from the EXPLORER-HCM study, the company has a U.S. PDUFA date of April 28, 2022.
In clinical and preclinical studies, mavacamten consistently reduced biomarkers of cardiac wall stress, decreased excessive cardiac contractility, increased diastolic compliance, and decreased left ventricular outflow tract (LVOT) gradients.
Mavacamten is an experimental 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 defeat serious diseases. For more information about Bristol Myers Squibb, visit us at BMS.com or follow us on LinkedIn, TwitterYoutube, Facebook and Instagram.
Caution Regarding Forward-Looking Statements
This press release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995 relating to, among other things, the research, development and marketing of pharmaceuticals. All statements that are not statements of historical fact are, or may be deemed to be, forward-looking statements. These 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, deflect or modify any of them in the next few years. years, which 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 or implied by the statements. These risks, assumptions, uncertainties and other factors include, among others, that the results of future studies will be consistent with results to date, that mavacamten may not receive regulatory approval for the indication described in this release in the currently anticipated time frame or at all, any marketing authorization, if granted, may have significant limitations as to its use and, if approved, whether the product candidate for the indication described in this release will a commercial success. No forward-looking statement can be guaranteed. The forward-looking statements contained in this press release must be evaluated together with the many risks and uncertainties that affect Bristol Myers Squibb’s business and market, particularly those identified in the Cautionary Note and Discussion of Risk Factors in the report. Annual Report of Bristol Myers Squibb on Form 10-K for the year ended December 31, 2021, as updated by our subsequent quarterly reports on Form 10-Q, our 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 required by applicable law, Bristol Myers Squibb undertakes no obligation to publicly update or revise any forward-looking statement, whether whether as a result of new information, future events, changed circumstances or otherwise.
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PUBLISHED: 03/04/2022 09:45 / DISK: 03/04/2022 09:46