Daprodustat HIF-PHI Therapy for Fatigue in Non-Dialysis CKD Anemia

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Solution Overview

Problem

Current treatments for anemia associated with chronic kidney disease do not effectively reduce fatigue in non-dialysis patients, with improvements in vitality being inconsistent and potentially clinically irrelevant.

Innovation Solution

Daprodustat or its pharmaceutically acceptable salts are used to treat anemia in non-dialysis patients, maintaining hemoglobin levels between 10-12 g/dL, leading to significant reductions in fatigue as measured by the SF-36 Vitality Domain and CKD-AQ Tired/Low Energy/Weak Domain scores.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If erythropoiesis-stimulating agents (ESAs) are used to treat anemia in CKD patients, then hemoglobin concentration increases, but improvement in fatigue and vitality is inconsistent and potentially clinically irrelevant

Engineering Contradiction:

Improvehemoglobin concentrationVSAvoidimprovement in fatigue and vitality

Core Design Contradiction:

Quantity of substanceVSReliability

Solution Approach 1:

The patent changes the therapeutic approach from ESAs to HIF-prolyl hydroxylase inhibitors (HIF-PHIs), which work through a different mechanism to stimulate erythropoiesis. This parameter change in the mode of action results in more reliable and clinically meaningful improvements in fatigue and vitality, with 68% of patients achieving ≥5-point improvement in SF-36 Vitality domain compared to inconsistent results with ESAs.

Inventive Principle:

Principle #35Parameter changes

2Adaptability or versatility

If generic HR-QoL instruments like SF-36 are used to assess quality of life, then broad health dimensions are covered, but disease-specific concerns and unique patient domains are not adequately captured

Engineering Contradiction:

Improvebroad health dimension coverageVSAvoiddisease-specific assessment accuracy

Core Design Contradiction:

Adaptability or versatilityVSMeasurement precision

Solution Approach 1:

The patent combines both generic (SF-36) and disease-specific (CKD-AQ) assessment instruments to evaluate health-related quality of life. This merging approach allows capturing both broad health dimensions and anemia-specific symptoms such as fatigue, weakness, and exercise tolerance, providing a comprehensive and precise assessment of patient outcomes.

Inventive Principle:

Principle #5Merging (Combining)

3Reliability

If HIF-prolyl hydroxylase inhibitors are used to treat anemia, then fatigue reduction is significantly improved, but treatment effectiveness varies by baseline inflammatory status (hsCRP levels)

Engineering Contradiction:

Improvefatigue reduction effectivenessVSAvoidresponse across different inflammatory states

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent identifies that patients with higher baseline inflammatory status (hsCRP≥6.60 mg/L) experience greater fatigue improvement (7.71-point increase in SF-36 Vitality) compared to those with lower inflammation. This local quality approach recognizes that treatment response varies by patient subgroup, allowing for tailored expectations and potentially adjusted dosing strategies based on inflammatory markers.

Inventive Principle:

Principle #3Local quality

Data Source

PatentUS20250319088A1Daprodustat for reducing fatigue in a subject with anemia associated with chronic kidney disease

Publication Date: 2025.10.16 GLAXOSMITHKLINE INTELLECTUAL PROPERTY (NO 2) LTD

AI summary

The present invention relates to daprodustat or a pharmaceutically acceptable salt thereof for use in reducing fatigue in non-dialysis subjects with anemia associated with chronic kidney disease. In particular embodiments, the invention is directed to particular subject populations in which the subject has hsCRP≥6.60 mg/L at baseline and in which the subject has a haemoglobin concentration of ≤11 g/dL at baseline.