Methods for increasing serum concentration of phosphorous and/or 1,25-hydroxy vitamin d
Inventors
Kakkis, Emil D. • San Martin, Javier • SUDO, Tomohiro
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-12358976-B2
Publication Date
2025-07-15
Expiration Date
Abstract
The present invention provides compositions and methods for treating a hypophosphatemic disorder, such as X-linked hypophosphatemia (XLH). The method entails administering to a subject a pharmaceutical composition containing an anti-FGF23 ligand, wherein the dosing regimen of the pharmaceutical is designed to reach effective and efficient control of FGF23 activity.
Core Innovation
The invention relates to methods of treating a subject having a hypophosphatemic disorder by administering an anti-FGF23 antibody about every two weeks. The method increases serum phosphorus levels and/or serum 1,25-dihydroxy vitamin D levels in a subject having a hypophosphatemic disorder, and the anti-FGF23 antibody comprises the CDR sequences of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6.
The document describes KRN23 clinical-study pharmacodynamics and pharmacokinetics in adult subjects with XLH. In adult XLH, serum phosphorus increases with each dosing interval, peaking around Day 7/14, while TmP/GFR increases in parallel, supporting renal phosphate reabsorption as the mechanism, and serum 1,25-dihydroxyvitamin D also increases with similar timing.
The pharmacokinetic analysis supports dose-proportional exposure and a linear correlation between KRN23 exposure (AUC) and changes in serum phosphorus, TmP/GFR, and 1,25(OH)2D. The document also describes an elimination half-life of about 16.4 days, correlations between exposure and biomarker changes, longer-term/extension design elements, and preliminary pediatric Phase 2 design comparing Q4 versus Q2 dosing.
Claims Coverage
The independent claim set comprises three independent methods that use an anti-FGF23 antibody with a defined CDR sequence composition and an administration frequency of about every two weeks. The inventive features are directed to increasing serum phosphorus levels, increasing serum 1,25-dihydroxy vitamin D levels, and increasing serum concentrations of phosphorus and/or 1,25-dihydroxy vitamin D in a subject with a hypophosphatemic disorder.
Anti-FGF23 antibody for increasing serum phosphorus
A method of increasing serum phosphorus levels in a subject having a hypophosphatemic disorder, comprising administering an effective amount of an anti-FGF23 antibody about every two weeks, wherein the anti-FGF23 antibody comprises the CDR sequences of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6.
Anti-FGF23 antibody for increasing serum 1,25-dihydroxy vitamin D
A method of increasing serum 1,25-dihydroxy vitamin D levels in a subject having a hypophosphatemic disorder, comprising administering an effective amount of an anti-FGF23 antibody about every two weeks, wherein the anti-FGF23 antibody comprises the CDR sequences of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6.
Anti-FGF23 antibody for increasing serum phosphorus and/or 1,25-dihydroxy vitamin D
A method of increasing serum concentrations of phosphorus and/or 1,25-dihydroxy vitamin D in a subject having a hypophosphatemic disorder, comprising administering an effective amount of an anti-FGF23 antibody about every two weeks, wherein the anti-FGF23 antibody comprises the CDR sequences of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6.
Overall, the claim coverage focuses on using a specifically defined anti-FGF23 antibody administered about every two weeks to increase serum phosphorus and/or serum 1,25-dihydroxy vitamin D in subjects with hypophosphatemic disorders.
Stated Advantages
Increases serum phosphorus levels in a subject having a hypophosphatemic disorder.
Increases serum 1,25-dihydroxy vitamin D levels in a subject having a hypophosphatemic disorder.
Increases serum concentrations of phosphorus and/or 1,25-dihydroxy vitamin D in a subject having a hypophosphatemic disorder.
Supports renal phosphate reabsorption as the mechanism.
Includes dose-proportional exposure and a linear correlation between KRN23 exposure (AUC) and changes in serum phosphorus, TmP/GFR, and 1,25(OH)2D.
Documented Applications
Clinical-study evaluation of KRN23 (anti-FGF23) pharmacodynamics and pharmacokinetics in adult XLH, including PK-PD relationships and changes in serum phosphorus, TmP/GFR, 1,25(OH)2D, and bone biomarkers.
Preliminary pediatric Phase 2 design comparing Q4 versus Q2 dosing, including preliminary data indicating steadier, less fluctuating increases under Q2 dosing and general tolerability.
Treatment of hypophosphatemic disorders, including X-linked hypophosphatemia (XLH), where the goal is increasing serum phosphorus levels and/or increasing serum 1,25-dihydroxy vitamin D levels.
Interested in licensing this patent?