USE OF BIOMARKERS OF INFLAMMATION AS INDICATORS OF DRUG EFFICACY

1 . A method for assessing the efficacy of a drug substance in a subject, comprising the steps of:

collecting a first biological sample from a subject prior to treatment with a drug substance;

exposing said first biological sample to an inflammatory agent, thereby inducing expression of an inflammation biomarker in said first sample;

measuring the level of said inflammation biomarker in said first biological sample;

administering said drug substance to said subject;

collecting a second biological sample from said subject following administration of said drug substance;

exposing said second biological sample to said inflammatory agent; and

measuring the level of said inflammation biomarker in said second biological sample,

wherein a decrease in the level of said inflammation biomarker in said second biological sample as compared to said first biological marker indicates that the drug substance is efficacious.

2 . The method of claim 1 , wherein the subject is enrolled in a clinical trial.

3 . The method of claim 2 , wherein the subject is enrolled in a Phase I clinical trial.

4 . The method of claim 1 , wherein the inflammatory agent is endotoxin.

5 . The method of claim 4 , wherein the inflammatory agent is LPS.

6 . The method of claim 1 , wherein the inflammation biomarker is a cytokine.

7 . The method of claim 6 , wherein the cytokine is TNF or IL-8.

8 . The method of claim 1 , wherein the steps of measuring the levels of inflammation biomarker is done at the level of mRNA.

9 . The method of claim 8 , wherein the steps of measuring the levels of inflammation biomarker is performed using real-time RT-PCR.

10 . The method of claim 9 , comprising the use of using SYBR Green or TaqMan® probes.

11 . The method of claim 1 , wherein the first and second biological samples comprise whole blood.

12 . The method of claim 1 , wherein the drug substance is a new chemical entity.

13 . The method of claim 1 , wherein the drug substance is a marketed drug.

14 . A kit for performing the method of claim 1 , comprising an inflammatory agent and means for measuring the level of the inflammation biomarker.

15 . The kit of claim 14 , wherein the means for measuring the level of the inflammation biomarker comprise RT-PCR.

16 . The kit of claim 15 , comprising amplification primers specific for the inflammation biomarker.

17 . The kit of claim 16 , further comprising control amplification primers, RNA extraction reagents, labeled probes, polymerases, nucleotides, buffers and combinations thereof.

18 . The method of claim 2 , wherein a dosing regimen for the drug substance is selected in a subsequent clinical trial.

19 . The method of claim 1 , wherein the dose of the drug substance is titrated in an individual subject.

20 . The method of claim 1 , further comprising assessing one or more of the following:

a) an effect of the inflammatory agent on the biological sample;

b) an anti-inflammatory effect of the drug substance in an individual subject;

c) an anti-inflammatory effect of the drug substance compared to placebo in a population of subjects;

d) an anti-inflammatory effect of the drug substance compared to the extent of the induced inflammatory response;

e) an anti-inflammatory effect of the drug substance compared to age in a population of subjects;

f) an anti-inflammatory effect of the drug substance compared to its side effects;

g) an anti-inflammatory effect of the drug substance in an individual subject over time; and

h) an anti-inflammatory effect of the drug substance compared to its AUC.