Recently, Liantuo Biotechnology announced that the National Drug Administration (NMPA) of China has accepted a new drug launch application (NDA) from Mavacamten for the treatment of adult patients with symptomatic obstructive hypertrophic cardiomyopathy (oHCM) and has included it in the priority review.
Mavacamten, as a clinically validated treatment regimen, is the first drug of its kind to treat obstructive hypertrophic cardiomyopathy. The submission of this new drug listing application is based on the data results of the global critical Phase III EXPLORER-HCM clinical trial conducted by Mavacamten. This trial evaluated the safety and efficacy of mavacamten in symptomatic oHCM patients compared to placebo. The results of EXPLORER-HCM test prove that mavacamten has a strong therapeutic effect, and can bring clinically significant improvements to patients in terms of motor ability, functional status, patient reporting outcomes, and ability to alleviate left Ventricular outflow tract obstruction. The EXPLORER-HCM trial achieved all of its pre-set primary and secondary study endpoints and was statistically significant.
This NDA also includes clinical data from the Mavacamten Phase I pharmacokinetic study conducted by Liantuo in Chinese healthy volunteers. This study demonstrates the safety, tolerability, and similar pharmacokinetic characteristics observed in phase I pharmacokinetic studies conducted in the United States for Mavacamten. The preliminary safety data of the Mavacamten Phase III double blind EXPLOR-CN trial being conducted by Liantuo in symptomatic oHCM Chinese patients are also used to support the submission of this NDA. The top line data of this trial is expected to be released in mid-2023.
HCM significantly affects the quality of life of patients, and there is currently a lack of effective treatment plans. Innovative drugs are urgently needed in clinical practice. As the first drug to target the pathophysiological mechanisms of diseases, mavacamten is expected to improve the treatment status of oHCM in China and have a positive impact on the health status and daily living ability of patients.
About Camzyos ™ (mavacamten)
Camzyos ™ Mavacamten is the first and currently the only myocardial myosin inhibitor approved by the US FDA, suitable for treating adult patients with symptomatic New York Heart Association (NYHA) grade II-III obstructive hypertrophic cardiomyopathy (oHCM) to improve functional ability and symptoms. In addition to being in the United States, the drug has also obtained regulatory approval for marketing in Australia, Canada, and Brazil. Camzyos is a selective allosteric reversible inhibitor of cardiac myosin. Camzyos regulates the number of myosin heads that can enter the state of "binding actin" (producing contractility), thus reducing the probability of dynamic generation (systolic period) and residual (diastole period) cross bridge formation. The mechanism of HCM is characterized by the formation of excessive myosin actin cross bridges and the imbalance of over relaxation. Camzyos transforms the overall myosin population into an energy-efficient and recyclable state of over relaxation. In HCM patients, inhibition of myosin with Camzyos reduces dynamic left Ventricular outflow tract (LVOT) obstruction and improves cardiac filling pressure.
In August 2020, Liantuo Biology obtained the license of MyoKardia, a wholly-owned subsidiary of Bristol Myers Squibb, to develop and commercialize Camzyos in Chinese Mainland, Hong Kong, Macao, Taiwan, Thailand and Singapore. In February 2022, mavacamten obtained breakthrough therapy qualification certification in China for the treatment of oHCM patients.
About EXPLORER-HCM
A total of 251 symptomatic (NYHA grade II or III) patients with obstructive hypertrophic cardiomyopathy were enrolled in the Phase III EXPLORER-HCM trial. The left Ventricular outflow tract (LVOT) differential pressure (resting and/or induced) of all subjects at screening was greater than or equal to 50mmHg.
The primary endpoint of EXPLORER-HCM is the composite functional endpoint, aimed at evaluating the improvement effect of mavacamten on patient symptoms and cardiac function. Secondary endpoints include changes in LVOT pressure difference from baseline to week 30, the proportion of subjects with at least one level of improvement in pVO2 and NYHA cardiac function, and changes in patient-reported outcome scale scores. Other endpoints include changes in echocardiographic indicators, circulating biomarkers, rhythm patterns, and acceleration from baseline to week 30.
About EXPLORER-CN
The Phase III EXPLORER-CN trial recruited a total of 81 symptomatic (NYHA grade II or III) patients with obstructive hypertrophic cardiomyopathy in China. The left Ventricular outflow tract (LVOT) differential pressure (resting and/or excitation) of all subjects at screening was greater than or equal to 50mmHg.
The main endpoint of the EXPLORER-CN study was the change in ValsalvaLVOT pressure difference from baseline to week 30. Secondary endpoints included changes in left Ventricular outflow tract (LVOT) obstruction from baseline to week 30, the proportion of subjects with at least one grade improvement in NYHA cardiac function, changes in patient reported outcome scale scores, cardiac biomarkers, and left ventricular mass index. Other endpoints include changes in echocardiography and cardiac magnetic resonance imaging indicators from baseline to week 30, as well as the proportion of subjects who achieved NYHA cardiac function improvement ≥ level 1 at week 30 and ValsalvaLVOT pressure difference<30mmHg at rest.
About hypertrophic cardiomyopathy
Hypertrophic cardiomyopathy is a chronic progressive disease caused by excessive myocardial contraction and obstruction of left ventricular blood filling, which can lead to symptoms of weakness and cardiac dysfunction. It is estimated that one out of every 500 people worldwide is a patient with hypertrophic cardiomyopathy. The most common cause of hypertrophic cardiomyopathy is mutations in myocardial sarcomere proteins. In patients with obstructive or non obstructive hypertrophic cardiomyopathy, strong physical activity can lead to fatigue or breathing difficulties, affecting the patient's daily life. Hypertrophic cardiomyopathy is also associated with an increased risk of atrial fibrillation, stroke, heart failure, and sudden cardiac death.
Currently, there are approximately 1.1 to 2.8 million patients with hypertrophic cardiomyopathy in China, of which approximately two-thirds are obstructive hypertrophic cardiomyopathy patients and one-third are non obstructive hypertrophic cardiomyopathy patients.
