Elagolix Dosing Regimen for Symptom Control With Lower BMD Loss

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Solution Overview

Problem

Current GnRH receptor antagonist treatments, such as elagolix, cause dose-dependent decreases in bone mineral density (BMD) that are not fully reversible, necessitating limited duration of use, posing a challenge in managing conditions like endometriosis, adenomyosis, PCOS, and uterine fibroids.

Innovation Solution

A dosing regimen for GnRH receptor antagonists, specifically Compound A or its pharmaceutically acceptable salts, involving a first treatment period with a higher dosage and frequency followed by a second period with a lower dosage and frequency to minimize BMD loss, potentially combined with hormone add-back therapy.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If higher dosage and frequency of GnRH receptor antagonist is administered, then symptom management efficacy is improved, but bone mineral density loss increases

Engineering Contradiction:

Improvesymptom management efficacyVSAvoidbone mineral density loss

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The treatment is divided into two distinct phases: an initial high-dose phase (200 mg twice daily) for symptom control, followed by a maintenance low-dose phase (150 mg once daily) to preserve bone density. This segmentation allows optimal symptom management while minimizing long-term bone loss through dose reduction.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The dosing regimen dynamically adjusts the dosage over time, transitioning from a higher initial dose to a lower maintenance dose. This dynamic approach optimizes therapeutic efficacy during the critical initial period while reducing bone density loss during extended treatment.

Inventive Principle:

Principle #15Dynamics

2Duration of action of stationary object

If duration of elagolix use is extended, then long-term symptom control is improved, but bone mineral density loss accumulates

Engineering Contradiction:

Improvetreatment durationVSAvoidcumulative bone mineral density loss

Core Design Contradiction:

Duration of action of stationary objectVSObject-affected harmful factors

Solution Approach 1:

The extended treatment duration is segmented into an initial 6-month high-dose phase and a subsequent low-dose maintenance phase. This allows patients to receive prolonged treatment for chronic conditions while limiting cumulative bone loss through reduced dosing in the maintenance phase.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The treatment employs periodic dosing adjustments, switching from intensive initial dosing to less intensive maintenance dosing. This periodic modification of treatment intensity enables long-term symptom control while periodically reducing the burden on bone density.

Inventive Principle:

Principle #19Periodic action

Data Source

PatentUS20260091036A1Dosing Regimens for Elagolix

Publication Date: 2026.04.02 ABBVIE INC

AI summary

The present invention relates to dosing regimens for GnRH receptor antagonists, and, in particular, dosing regimens for 4-((R)-2-[5-(2-fluoro-3-methoxy-phenyl)-3-(2-fluoro-6trifluoromethyl-benzyl)-4-methyl-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-yl]-1-phenylethylamino)-butyric acid (Compound A) or a pharmaceutically acceptable salt thereof, in subjects suffering from, for example, endometriosis, adenomyosis, polycystic ovary syndrome (PCOS), or uterine fibroids, to minimize changes in bone mineral density associated with such GnRH receptor antagonists.