- EXPLORER-CN data presented in oral late-breaking science session at ESC 2023
- Data from the trial published simultaneously in JAMA Cardiology
- Mavacamten demonstrated improvement in Valsalva LVOT peak gradient, LVOT obstruction, clinical symptoms, health status, cardiac biomarkers, and cardiac structure in Chinese oHCM patients
- Study confirms previously established efficacy of mavacamten can be extended to Chinese patients
SHANGHAI, China and PRINCETON, N.J., Aug. 28, 2023 (GLOBE NEWSWIRE) — LianBio (Nasdaq: LIAN), a biotechnology company dedicated to bringing innovative medicines to patients in China and other major Asian markets, today announced data from the Phase 3 EXPLORER-CN trial of mavacamten in Chinese symptomatic obstructive hypertrophic cardiomyopathy (oHCM) patients were presented in a late-breaking science session at the European Society of Cardiology (ESC) Congress 2023 and simultaneously published in a JAMA Cardiology paper titled, “Effect of Mavacamten on Chinese Patients With Symptomatic Obstructive Hypertrophic Cardiomyopathy.”
LianBio previously announced topline data from EXPLORER-CN, with mavacamten demonstrating statistically significant and clinically meaningful improvement in Valsalva left ventricular outflow tract (LVOT) peak gradient, the study’s primary endpoint. Mavacamten also demonstrated improvement across all secondary endpoints, including LVOT obstruction, clinical symptoms, and health status.
The data presented at ESC 2023 and published in JAMA Cardiology continue to demonstrate robust evidence of mavacamten’s therapeutic benefit. New data published today provide additional detail showing mavacamten’s impact on reducing cardiac biomarkers associated with poor prognosis in oHCM, and improvement in biomarkers associated with cardiac structure remodeling. In addition, the study demonstrated mavacamten’s efficacy across prespecified subgroups, including beta-blocker usage, sex, age, body mass index, New York Heart Association (NYHA) class, and CYP2C19 metabolizer phenotype.
“EXPLORER-CN demonstrates mavacamten’s broad treatment effect in oHCM,” said Zhuang Tian, M.D., Professor of Cardiology, and Deputy Director of the International Medical Department, Peking Union Medical College Hospital, and EXPLORER-CN Investigator. “With improvement seen across LVOT obstruction, clinical symptoms, health status, cardiac biomarkers, and cardiac structure, mavacamten has the potential to be a meaningful new treatment options for patients in China.”
The randomized, controlled, Phase 3 EXPLORER-CN trial enrolled 81 patients with symptomatic oHCM. All patients had significant LVOT obstruction at baseline. The mean left ventricular ejection fraction (LVEF) was similar between the mavacamten and placebo groups. Most patients were receiving background beta-blockers in both groups.
As previously reported, EXPLORER-CN met its primary endpoint, demonstrating a statistically significant and clinically meaningful improvement in Valsalva LVOT peak gradient compared to placebo after 30 weeks of treatment (least-squares mean difference, −70.29 mm Hg; 95% CI, −89.64 to −50.94; 1-sided p< .001). The reduction in Valsalva LVOT peak gradient with mavacamten treatment started as early as 4 weeks and was sustained through week 30. Data published today showed consistent benefit for the primary endpoint was observed across prespecified subgroups, regardless of beta-blocker use or CYP2C19 phenotype.
Among the new data published today, cardiac biomarkers decreased with mavacamten treatment from week 4 and were sustained throughout the study period. At week 30, reduction in N-terminal pro-B-type natriuretic peptide (NT-proBNP) was 82% greater for mavacamten compared with placebo (proportion of geometric mean ratio [GMR], 0.18; 95% CI, 0.13 to 0.24). Reduction in high-sensitivity cardiac troponin I (hs-cTnI) was 66% greater in the mavacamten group compared with placebo (proportion of GMR, 0.34; 95% CI, 0.27 to 0.42). NT-proBNP and cardiac troponin are biomarkers of cardiac wall stress and myocardial injury that have been associated with poor clinical outcomes, including heart failure, atrial fibrillation, and death in HCM patients.
Improvements in cardiac structure were also observed in patients treated with mavacamten. Among 58 eligible patients with cardiac magnetic resonance (CMR) data available, secondary and exploratory CMR endpoints revealed favorable markers for cardiac remodeling with mavacamten from baseline to week 30, including reductions in left ventricular mass index (LVMI) (mean difference, −30.80 g/m2; 95% CI, −41.55 to −20.05), left ventricular mass (mean difference, −52.64 g; 95% CI, −67.89 to −37.39), maximum left atrial volume index (mean difference, −18.27 mL/m2; 95% CI, −26.72 to −9.83), and left ventricular maximal wall thickness (mean difference, −3.52 mm; 95% CI, −4.65 to −2.38), all of which are predictors of poor outcomes in oHCM.
As previously reported, safety results in the trial were consistent with previous studies of mavacamten in symptomatic oHCM, and no new safety signals were reported. Resting LVEF remained stable in both groups throughout treatment, and no participants in the study experienced decreases in LVEF <50 % that required dose interruption.
In April 2023, the China National Medical Products Administration (NMPA) accepted with Priority Review a New Drug Application (NDA) for mavacamten for the treatment of adults with symptomatic oHCM.
“Mavacamten is the first pharmacological tool developed to specifically target the underlying pathophysiology of oHCM in China,” said Michael Humphries, FRCP, Chief Scientific Advisor and Head of General Medicine Development, LianBio. “The EXPLORER-CN trial demonstrates that the well-established therapeutic benefit of this drug also extends to Chinese patients. We thank the EXPLORER-CN patients and investigators for their dedication to this study and look forward to making mavacamten available to oHCM patients in China in the coming year.”
Camzyos® (mavacamten) is the first and only cardiac myosin inhibitor approved by the U.S. FDA, indicated for the treatment of adults with symptomatic New York Heart Association (NYHA) class II-III obstructive 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 LVOT obstruction and improves cardiac filling pressures.
LianBio licensed rights from MyoKardia, now a wholly owned subsidiary of Bristol Myers Squibb, in August 2020 for the development and commercialization of mavacamten in Mainland China, Hong Kong, Macau, Taiwan, Thailand and Singapore. Mavacamten was granted Breakthrough Therapy Designation in China for the treatment of patients with oHCM in February 2022.
The Phase 3 EXPLORER-CN trial enrolled a total of 81 Chinese patients with symptomatic (NYHA Class II or III) oHCM. All participants had one measurable LVOT gradient (resting or Valsalva) >50 mmHg during screening. Patients were randomized 2:1 to mavacamten or placebo.
The primary endpoint for EXPLORER-CN is the change from baseline to week 30 in Valsalva LVOT peak gradient. Secondary endpoints include change from baseline to week 30 in resting LVOT peak gradient, proportion of participants achieving a Valsalva LVOT peak gradient <30 mmHg at week 30, proportion of participants achieving a Valsalva LVOT peak gradient <50 mmHg at week 30, proportion of participants with at least one NYHA class improvement from baseline to week 30, change from baseline to week 30 in Kansas City Cardiomyopathy Questionnaire (KCCQ) Clinical Summary Score (CSS), change from baseline to week 30 in NT-proBNP, change from baseline to week 30 in cardiac troponin, and change from baseline to week 30 in left ventricular mass index evaluated by cardiac magnetic resonance imaging.
More information about the EXPLORER-CN trial can be found on ClinicalTrials.gov (NCT05174416) or http://www.chinadrugtrials.org.cn/index.html (CTR20212890).
About Hypertrophic Cardiomyopathy
Hypertrophic cardiomyopathy (HCM) is a chronic, progressive disease in which excessive contraction of the heart muscle and reduced ability of the left ventricle to fill can lead to the development of debilitating symptoms and cardiac dysfunction. HCM is estimated to affect one in every 500 people globally. The most frequent cause of HCM is mutations in the heart muscle proteins of the sarcomere. In patients with both obstructive and non-obstructive HCM, exertion can result in fatigue or shortness of breath, interfering with a patient’s ability to participate in activities of daily living. HCM has also been associated with increased risks of atrial fibrillation, stroke, heart failure and sudden cardiac death.
In China, there are an estimated 1.1 million to 2.8 million patients with HCM.
LianBio is a cross-border biotechnology company on a mission to bring transformative medicines to historically underserved patients in China and other Asian markets. Through partnerships with highly innovative biopharmaceutical companies around the world, LianBio is advancing a diversified portfolio of clinically validated product candidates with the potential to drive new standards of care across cardiovascular, oncology, ophthalmology, and inflammatory disease. LianBio is establishing an international infrastructure to position the company as a partner of choice with a platform to provide access to China and other Asian markets. For more information, please visit www.lianbio.com.
Cautionary Note Regarding Forward-Looking Statements
Statements in this press release about future expectations, plans and prospects, as well as any other statements regarding matters that are not historical facts, may constitute forward-looking statements. The words “may”, “continue,” “estimate,” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Forward-looking statements in this press release include, but are not limited to, statements regarding LianBio’s plans to make mavacamten available to oHCM patients in China in the coming year. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including: LianBio’s ability to successfully initiate and conduct its planned clinical trials and complete such clinical trials and obtain results on its expected timelines, or at all; LianBio’s plans to leverage data generated in its partners’ global registrational trials and clinical development programs to obtain regulatory approval and maximize patient reach for its product candidates; LianBio’s ability to identify new product candidates and successfully acquire such product candidates from third parties; competition from other biotechnology and pharmaceutical companies; general market conditions; the impact of changing laws and regulations and those risks and uncertainties described in LianBio’s filings with the U.S. Securities and Exchange Commission (SEC), including LianBio’s Annual Report on Form 10-K for the year ended December 31, 2022 and subsequent filings with the SEC. Any forward-looking statements contained in this press release speak only as of the date hereof, and LianBio specifically disclaims any obligation to update any forward-looking statement, whether as a result of new information, future events or otherwise. Readers should not rely upon this information as current or accurate after its publication date.
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