Genome-based methods for reducing cardiovascular risk

Patent metadata

Field	Value
Publication number	US-12264366-B2
Application number	US-202016876030-A
Country	US
Kind code	B2
Filing date	May 16, 2020
Priority date	May 17, 2019
Publication date	Apr 1, 2025
Grant date	Apr 1, 2025

Abstract

The present disclosure provides methods of reducing cardiovascular risk by administration of a PCSK9 inhibitor to patients having a genetic profile associated with response to PCSK9 inhibitor therapy.

First claim

What is claimed is:

1. A method of treating a patient who has received or is currently receiving an intensive statin therapy treatment, and who has a high genetic risk of recurrent major adverse cardiovascular event (MACE) despite intensive statin therapy, comprising administering a proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitor to the patient, wherein the patient:
does not have elevated levels of lipoprotein(a) (LPA or LP (a)) or LDL-C; and
has a coronary artery disease polygenic risk score (CAD-PRS) greater than the 90 th percentile determined from a reference population, wherein the CAD-PRS comprises a weighted sum of a plurality of genetic variants associated with coronary artery disease;
wherein the patient receiving the PCSK 9 inhibitor demonstrates reduced absolute and relative risk of developing recurring MACE compared to a patient with the same CAD-PRS receiving placebo treatment.

2. The method according to claim 1 , wherein the CAD-PRS threshold score is the top 95% within a reference population.

3. The method according to claim 1 , wherein the reference population comprises at least 100 patients.

4. The method according to claim 1 , wherein the plurality of genetic variants is determined by calculating genetic variant performance in the reference population and selecting the highest performing genetic variants.

5. The method according to claim 4 , wherein genetic variant performance is calculated with respect to coronary artery disease risk based on statistical significance, strength of association, and/or a probability distribution.

6. The method according to claim 5 , wherein the CAD-PRS is calculated using LDPred method.

7. The method according to claim 5 , wherein the CAD-PRS is calculated using pruning and thresholding method.

Assignees

• Regeneron Pharma

Inventors

• Damask Amy
• Paulding Charles
• Baras Aris
• Abecasis Goncalo

Classifications

• A61P3/00

  Drugs for disorders of the metabolism (of the blood or the extracellular fluid A61P7/00) · CPC title

• C07K2317/76

  Antagonist effect on antigen, e.g. neutralization or inhibition of binding · CPC title

• C07K2317/21

  from primates, e.g. man · CPC title

• G16B20/00

  ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations · CPC title

• G16B40/20

  Supervised data analysis · CPC title