Methods for establishing a vedolizumab dosing regimen to treat patients with irritable bowel disease
Inventors
Singh, Sharat • Jain, Anjali • Kondragunta, Venkateswarlu
Assignees
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Publication Number
US-10324088-B2
Publication Date
2019-06-18
Expiration Date
Abstract
The present invention provides methods for predicting whether an individual having inflammatory bowel disease (IBD) is likely to respond to vedolizumab treatment. Also provided are methods for predicting whether an individual with IBD such as Crohn's disease or ulcerative colitis will develop autoantibodies against vedolizumab. The present invention also provides a treatment regimen for an IBD patient which includes measuring the level of one or more predictive markers of response to vedolizumab prior to administering the anti-α4β7 integrin drug.
Core Innovation
The disclosed invention relates to individualized therapy regimens for an anti-α4β7 integrin drug, where the anti-α4β7 integrin drug is ENTYVIO® (vedolizumab), in a subject suffering from inflammatory bowel disease (IBD). The therapy regimen includes measuring the presence or level of at least two predictive markers selected to include MAdCAM-1 and VCAM-1, and optionally includes a marker selected from TNFα, human serum albumin (HSA), VEGF, angiopoietin-1 (ANG-1), angiopoietin-2 (ANG-2), adenosine deaminase (ADA), serum α4β7 integrin, IL-12p40, C-reactive protein (CRP), MMP9, ICAM-1, or combinations thereof.
The invention uses the measured predictive markers to define a predictive marker profile compared to a corresponding reference value. The reference value is the mean concentration of the markers in patients with IBD prior to initiation of vedolizumab. Based on the predictive marker profile, the regimen determines whether to administer ENTYVIO® (vedolizumab) by evaluating a lower level of the at least two predictive markers compared to the reference value.
If the subject does not meet the criterion based on lower levels of the predictive markers compared to the reference value, the regimen provides for administering an alternative therapy for IBD or maintaining an existing IBD therapy. The disclosed regimen further includes predicting whether a subject will develop autoantibodies against the anti-α4β7 integrin drug by applying statistical analysis to the predictive marker profile, using later time-point sampling.
Claims Coverage
The independent claim covers a therapy regimen for ENTYVIO® (vedolizumab) in IBD that is governed by measuring predictive biomarkers for a decision between vedolizumab administration and alternative or maintenance therapy. The inventive feature set includes explicit level comparisons, expanded biomarker panels, sample-type specification, statistical prediction of autoantibody development, and restriction to UC or Crohn’s disease.
Predictive marker-guided ENTYVIO therapy regimen for IBD
A therapy regimen for an anti-α4β7 integrin drug wherein the anti-α4β7 integrin drug is ENTYVIO® (vedolizumab), comprising measuring the presence or level of at least two predictive markers of MAdCAM-1 and VCAM-1 (optionally, a marker selected from TNFα, HSA, VEGF, ANG-1, ANG-2, ADA, serum α4β7 integrin, IL-12p40, CRP, MMP9, ICAM-1, or a combination) in a sample from a subject suffering from IBD, and administering ENTYVIO® (vedolizumab) according to a predictive marker profile based on a lower level of the at least two predictive markers compared to a reference value; otherwise administering an alternative therapy for IBD to said subject or maintaining an existing IBD therapy.
Lower-than-reference criterion for vedolizumab administration
The therapy regimen specifies that administering ENTYVIO® (vedolizumab) is based on a lower level of the at least two predictive markers compared to a corresponding reference value, wherein the reference value is the mean concentration of said markers in patients with IBD prior to initiation of vedolizumab.
Expanded predictive marker panel with alternative-therapy contingency
The therapy regimen further measures TNFα, VEGF, ANG-2, and CRP levels and administers an alternate IBD therapy if the measured levels of TNFα, VEGF, ANG-2, CRP, and/or VCAM-1 are higher than corresponding reference values.
Predictive marker measurement using whole blood, serum, or plasma
The therapy regimen includes using a sample selected from whole blood, serum, or plasma for measuring the predictive markers.
Statistical prediction of autoantibodies against ENTYVIO
The therapy regimen applies statistical analysis to a predictive marker profile to predict whether a subject will develop autoantibodies against the anti-α4β7 integrin drug.
IBD indication restricted to UC or Crohn’s disease
The therapy regimen is for inflammatory bowel disease that is either ulcerative colitis (UC) or Crohn's disease (CD).
Overall, the claim set focuses on guiding ENTYVIO® (vedolizumab) therapy in IBD using a predictive marker profile based on MAdCAM-1 and VCAM-1, optionally with additional specified markers, compared against a reference mean from IBD patients prior to vedolizumab. It also provides contingencies for alternative or maintenance therapy and includes dependent claim refinements involving expanded biomarker panels, sample type, statistical prediction of autoantibody development, and restriction to UC or CD.
Stated Advantages
Documented Applications
Managing individualized ENTYVIO® (vedolizumab) therapy regimens in inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), by measuring predictive biomarkers and using a reference value to determine whether to administer vedolizumab or alternative or maintenance IBD therapy.
Predicting whether a subject will develop autoantibodies against the anti-α4β7 integrin drug using statistical analysis of a predictive marker profile with later time-point sampling.
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