Methods of treating heart failure with cardiac sarcomere activators
Inventors
Honarpour, Narimon • Malik, Fady
Assignees
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Publication Number
US-12295952-B2
Publication Date
2025-05-13
Expiration Date
Abstract
Provided herein are methods of treating a subject with heart failure, comprising administering to the subject an initial dose of a cardiac sarcomere activator (CSA) for an initial time period, and subsequently administering to the subject a dose of the CSA based on the subject's plasma concentration of the CSA at the end of the initial time period.
Core Innovation
The invention relates to methods of determining a treatment regimen for a subject with heart failure using a cardiac sarcomere activator. The method comprises administering an initial dose of the cardiac sarcomere activator for an initial time period, determining the subject’s plasma concentration of the cardiac sarcomere activator at about 2 weeks after the first administration, and determining a treatment regimen based on the measured plasma concentration.
The cardiac sarcomere activator is omecamtiv mecarbil, or a pharmaceutically acceptable salt thereof. The method selects a subsequent dose for a second time period based on plasma concentration thresholds, including a threshold concentration of 300 ng/mL to decide whether the dose subsequently administered is greater than the initial dose.
In embodiments, the treatment regimen includes oral administration and concentration-based dose selection to choose among dose levels of about 25 mg twice daily, about 37.5 mg twice daily, or about 50 mg twice daily. The regimen ties each twice-daily dose level to whether the subject’s plasma concentration is greater than or about 300 ng/mL, greater than or about 200 ng/mL but less than 300 ng/mL, or less than 200 ng/mL.
Claims Coverage
The partial content includes three independent claims. Each independent claim covers a plasma-concentration-guided determination of a heart failure treatment regimen using a cardiac sarcomere activator, with an initial dose and a subsequent dosing decision based on plasma concentration measured at about 2 weeks.
Initial csa dosing with concentration measurement at about 2 weeks
Administering to the subject an initial dose of a cardiac sarcomere activator for an initial time period, determining the subject's plasma concentration of the cardiac sarcomere activator at about 2 weeks after the first administration of the initial dose, and determining a treatment regimen based on the subject's plasma concentration.
Dose escalation rule based on a 300 ng/mL threshold
When the subject's plasma concentration of the cardiac sarcomere activator is less than a threshold concentration of 300 ng/mL, the dose subsequently administered to the subject is greater than the initial dose.
Omecamtiv mecarbil CSA as the therapeutic agent
The cardiac sarcomere activator is omecamtiv mecarbil, or a pharmaceutically acceptable salt thereof.
Three-tier concentration-to-dose mapping for a second time period
Selecting the dose subsequently administered to the subject as about 25 mg twice daily when the subject's plasma concentration is greater than or about 300 ng/mL; about 37.5 mg twice daily when the subject's plasma concentration is greater than or about 200 ng/mL but less than 300 ng/mL; or about 50 mg twice daily when the subject's plasma concentration is less than 200 ng/mL.
Fixed initial time period and oral administration
Administering the initial dose of about 25 mg twice daily for an initial time period of about 4 weeks, and the cardiac sarcomere activator is orally administered to the subject.
Overall, the independent claims cover a method in which an initial cardiac sarcomere activator dose is administered for an initial time period, the plasma concentration is determined at about 2 weeks, and a subsequent dosing regimen for a second time period is selected using explicit plasma concentration thresholds to choose among specified twice-daily dose levels.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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