Methods for treating tumor-induced osteomalacia
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-11771748-B2
Publication Date
2023-10-03
Expiration Date
Abstract
The present invention provides compositions and methods for treating tumor-induced osteomalacia. 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 anti-FGF23 ligand therapy for FGF23-associated phosphate disorders, including tumor-induced osteomalacia (TIO), by administering an anti-FGF23 antibody. The therapy is described in terms of treating a subject in need and maintaining phosphate control across dosing cycles. The approach centers on using pharmacodynamic (PD) parameters to guide dosing regimens rather than relying only on fixed scheduling.
A key aspect is determining dosing regimens using PD biomarkers of phosphate metabolism and related pathways, including serum phosphorus exposure measures such as AUC and peak/trough, TmP/GFR, and vitamin D parameters including 1,25-dihydroxy and 25-hydroxy vitamin D. The goal is to achieve stable and adequate phosphate control over dosing cycles, including maintaining serum phosphorus at target levels across time between administrations.
The document further describes marker-based assessment of increased bone remodeling in the context of phosphate control, with examples including bone remodeling-related markers and trends for bone formation/resorption biomarkers. It also describes pharmacokinetics (PK) and PK-PD relationships, including correlations between exposure and PD changes, as part of evaluating the dosing regimen and treatment effect. Extensive clinical trial example data for KRN23 in adult XLH are provided to support the observed sustained increases in serum phosphorus and related PD measures over dosing cycles.
Claims Coverage
The independent claim covers a TIO treatment method using an anti-FGF23 antibody administered about every two weeks, with the antibody characterized by specific CDR sequences. Dependent claims further narrow the antibody sequences and administration and patient/dose parameters.
Anti-FGF23 antibody for treating tumor-induced osteomalacia
A method of treating tumor-induced osteomalacia (TIO) by administering an effective amount of an anti-FGF23 antibody to a subject in need.
About every two weeks dosing schedule
Administering the anti-FGF23 antibody to the subject about every two weeks.
CDR sequence-defined antibody
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.
Specific heavy-chain sequence
The heavy chain of the anti-FGF23 antibody contains the sequence SEQ ID NO: 7.
Specific light-chain sequence
The light chain of the anti-FGF23 antibody contains the amino acid sequence SEQ ID NO: 8.
Subcutaneous administration
Administering the anti-FGF23 antibody subcutaneously.
Pediatric patient population
Performing the method on a pediatric subject.
About 0.4 mg/kg dosing
Administering the anti-FGF23 antibody at a dose of about 0.4 mg/kg.
Overall, the claim set centers on treating TIO with a specific CDR-defined anti-FGF23 antibody given on an about every-two-weeks schedule, with further limitations that specify particular heavy- and light-chain sequences, subcutaneous administration, a pediatric patient population, and a dose constraint.
Stated Advantages
Achieve stable, adequate phosphate control over dosing cycles using PD biomarkers.
Maintain serum phosphorus control across dosing cycles based on serum phosphorus exposure measures and related PD parameters.
Provide correlated PK-PD relationships between exposure and PD changes.
Trends toward changes in bone formation/resorption biomarkers and marker-based assessment of increased bone remodeling.
Improved quality-of-life measures and a generally favorable safety profile.
Documented Applications
Treating tumor-induced osteomalacia (TIO) by administering an effective amount of an anti-FGF23 antibody.
Therapy evaluation in adult XLH using KRN23 and repeat-dose subcutaneous dosing with sustained PD effects on serum phosphorus and related biomarkers.
Interested in licensing this patent?