Pipeline Drugs for Heart Disease


Heart disease is the leading cause of death for both men and women. Coronary heart disease (CHD) is the most common type of heart disease. For some people, the first sign of CAD is a heart attack. CAD is caused by plaque buildup in the walls of the arteries that supply blood to the heart. Plaque buildup causes the inside of the arteries to narrow over time, which could partially or totally block the blood flow. This process is called atherosclerosis.

Medications to treat the risk factors for CAD, such as high cholesterol, high blood pressure, an irregular heartbeat, and low blood flow. -- The most commonly prescribed high cholesterol medications are the statins. Statins work by blocking a substance that the liver needs to produce cholesterol, which allows the liver to remove the cholesterol from the blood. These drugs can potentially reverse coronary artery disease as well, by enabling the body to reabsorb cholesterol from built-up deposits that have been collected along the walls of the arteries. The Statin options that are generally prescribed by doctors are atorvastatin (Lipitor), fluvastatin (Lescol), rosuvastatin (Crestor), pitavastatin (Livalo), simvastatin (Zocor), lovastatin (Altoprev, Mevacor) and pravastatin (Pravachol). Statins have been a mainstay of heart attack and stroke prevention for the past 20 years, but the race is on to bring a new drug to market that targets an enzyme called PCSK9. The PCSK9 inhibitors are a new class of drugs that have been shown to dramatically lower LDL cholesterol levels. PCSK9 inhibitors are monoclonal antibodies (MABs), a type of biologic drug. They inactivate a protein in the liver called proprotein convertase subtilisin kexin 9 (PCSK9) Read more at: https://tr.im/Pe2at

Pipeline Drugs for PCSK9 --Pfizer is currently developing PCSK9 pill and vaccine to lower cholesterol . Evolocumab is a fully human monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9) and is from Amgen. Evolocumab is designed to bind to PCSK9 and inhibit PCSK9 from binding to LDL receptors on the liver surface. See: FDA approves Repatha (evolocumab) to treat certain patients with high cholesterol. Amgen's low-density lipoprotein cholesterol-lowering medication is in direct competition with Sanofi/RegeneronPharmaceuticals's alirocumab. See: FDA approves Praluent (alirocumab) to treat certain patients with high cholesterol. Industry analysts forecast billions of dollars of peak annual sales for both products. Studies using a vaccine to lower cholesterol are still in the pipeline.

What is the role of PCSK9? --In the liver, the LDL receptor removes LDL cholesterol from the blood. When PCSK9 binds to the LDL receptor, the receptor is broken down and can no longer remove LDL cholesterol from the blood. If PCSK9 is blocked, more LDL receptors will be present on the surface of the liver and will remove more LDL cholesterol from the blood.[2] Therefore, blocking PCSK9 can lower blood cholesterol levels.[3][4] Similar genes (orthologs) are found across many species. PCSK9 is inactive when first synthesized, because a section of peptide chains blocks their activity; proprotein convertases remove that section to activate the enzyme.

Congestive Heart Failure (CHF), occurs when the heart is unable to pump sufficiently to maintain blood flow to meet the body's needs. Common causes of heart failure include coronary artery disease including a previous myocardial infarction (heart attack), high blood pressure, atrial fibrillation, valvular heart disease, excess alcohol use, infection, and cardiomyopathy of an unknown cause.

Enresto by Novartis was approved in July 2015. Entresto is a combination of sacubitril, a neprilysin inhibitor, and valsartan, an angiotensin II receptor blocker. Entresto is specifically indicated to reduce the risk of cardiovascular death and hospitalization for heart failure in patients with chronic heart failure (NYHA Class II-IV) and reduced ejection fraction.

Bayer is pushing forward with a new heart-failure treatment that could eventually contend with Novartis' ($NVS) blockbuster-in-waiting Entresto, mapping out a wide Phase III program for its oral drug. The pill, finerenone, is a next-generation mineralocorticoid receptor antagonist, or MRA, designed to block the production of bodily steroids that degrade heart function and lead to kidney problems