EYP001 Once-Daily Dosing to Reduce FXR Agonist Pruritus
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Solution Overview
Problem
Current FXR agonists, such as obeticholic acid, used for treating chronic liver diseases like primary biliary cholangitis, are associated with high rates of pruritus, a symptom that compromises their use, and the mechanism of this adverse effect is not well understood.
Innovation Solution
Administering the FXR agonist EYP001 once a day, rather than twice a day, reduces the frequency and severity of pruritus while maintaining therapeutic benefits, particularly in the treatment of NASH and chronic hepatitis B.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If FXR agonists are administered twice a day, then therapeutic efficacy is maintained, but pruritus frequency increases
Solution Approach 1:
The patent applies periodic action by transitioning from twice-daily administration to once-daily administration of EYP001. This change in dosing frequency reduces the accumulation of the drug in the system, thereby decreasing pruritus frequency while maintaining therapeutic efficacy through optimized periodic dosing.
Solution Approach 2:
The patent changes the dosing parameter from twice-daily to once-daily administration. This parameter modification optimizes the balance between therapeutic effect and adverse effects, reducing pruritus occurrence while preserving the beneficial therapeutic actions of the FXR agonist.
2Reliability
If FXR agonists are administered at higher doses, then therapeutic benefits increase, but pruritus severity increases
Solution Approach 1:
The patent optimizes the dosing parameter by switching from twice-daily to once-daily administration. This parameter change allows for reduced total daily dose while maintaining therapeutic benefits, thereby decreasing pruritus severity through optimized dosing parameters.
Solution Approach 2:
By changing the periodicity of administration from twice-daily to once-daily, the patent reduces peak plasma concentrations and overall drug exposure, which correlates with reduced pruritus severity while maintaining adequate therapeutic response.
3Reliability
If FXR agonists are administered continuously, then disease control is maintained, but quality of life decreases due to pruritus
Solution Approach 1:
The patent improves quality of life by changing from continuous twice-daily dosing to once-daily dosing. This reduced frequency of administration maintains disease control while significantly reducing the burden of pruritus and improving patient comfort and daily functioning.
Solution Approach 2:
The patent extracts the harmful effect (pruritus) from the continuous treatment regimen by optimizing the dosing frequency. This allows the therapeutic benefits to be maintained while separating and reducing the adverse effects through once-daily administration.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
This dosing regimen decreases pruritus occurrence by up to four times compared to twice-daily administration, enhancing the efficacy and benefit-risk ratio for long-term treatments of chronic diseases.
Implementation Method 1
EYP001 is an FXR agonist and the inventors surprisingly identified a dosing regimen allowing a decrease in the frequency of the pruritus occurring during a treatment with EYP001
Data Source
AI summary
The present invention relates to a method of treatment with an FXR agonist allowing to decrease pruritus and improve efficacy.