CFTR Modulator Combination Therapy for Cystic Fibrosis
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Solution Overview
Problem
Current treatments for cystic fibrosis, particularly those involving CFTR correctors, are not sufficiently effective, necessitating the development of novel CFTR modulators to enhance ion transport and address the underlying ion and fluid transport imbalances in patients with CFTR-mediated diseases.
Innovation Solution
The use of (6R)-17-amino-12,12-dimethyl-6,15-bis(trifluoromethyl)-19-oxa-3,4,13,18-tetrazatricyclo[12.3.1.12,5]nonadeca-1(18),2,4,14,16-pentaen-6-ol (Compound I) and its deuterated derivatives, along with other CFTR-modulating agents, to modulate CFTR activity and improve ion transport in respiratory and digestive tissues.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If CFTR correctors are used to improve faulty protein processing and trafficking, then CFTR activity is enhanced, but monotherapy is not effective enough and combination therapy with potentiators is needed
Solution Approach 1:
The patent combines multiple CFTR modulators (correctors and potentiators) into a single pharmaceutical composition, merging their effects to achieve synergistic enhancement of CFTR activity while simplifying the treatment regimen from sequential monotherapies to a unified combination therapy
2Reliability
If only one CFTR potentiator is approved for treatment, then regulatory approval is achieved, but there is a need for novel treatments to address limitations of current therapy
Solution Approach 1:
The patent introduces a novel CFTR potentiator with a specific chemical structure featuring a 1,2,4-triazole ring system and fluorinated aromatic groups, representing a parameter change in the molecular structure of CFTR modulators to achieve improved or alternative therapeutic effects compared to existing approved potentiators
Data Source
AI summary
This disclosure provides methods of treating cystic fibrosis or a CFTR-mediated disease comprising administering Compound I, a deuterated derivative thereof, or a pharmaceutically acceptable salt of any of the foregoing, e.g., administering about 1 mg to about 400 mg of Compound I. The disclosure also provides pharmaceutical compositions comprising Compound I, a deuterated derivative thereof, or a pharmaceutically acceptable salt of any of the foregoing, and optionally comprising one or more additional CFTR-modulating agents.