Introduction

In 1955, the lipid lowering properties of niacin were first reported. Niacin is thus the first agent of this therapeutic class; subsequently there have been introductions of extended release formulations of niacin, niacinamide, and combinations with previously approved drugs. Since the late 1960s, with the approval of Atromid-S (clofibrate) in 1967, there have been a total of 19 new drugs approved for lipid or cholesterol lowering, in 7 pharmacologic classes. The most successful of these by far have been the HMG-CoA reductase inhibitors or statins, starting two decades later, with the approval of Mevacor (lovastatin) in 1987.

Drug Approvals

The 19 new drugs approved for lipid or cholesterol lowering and the 7 pharmacologic classes are shown in the chart below (click for a larger chart). See list of proprietary and established names for the approved drugs at the end.

• Fibrates, or PPAR (peroxisome proliferator-activated receptor) Activators: 3 new drugs; over 26 years & 7 months; between 1967 and 1993
• Bile Acid Sequestrants, or Ion Exchange Resins: 3 new drugs; over 26 years & 9 months; between 1973 and 2000
• HMG-CoA Reductase Inhibitors, or Statins: 8 new drugs (one withdrawn from the market); over 21 years & 11 months; between 1987 and 2009
• Cholesterol Absorption Inhibitors: 1 new drug; in 2002
• Microsomal Triglyceride Transfer Protein Inhibitors: 1 new drug (orphan drug approval); in 2012
• Apolipoprotein B-100 Syntheses Inhibitors: 1 new drug (orphan drug approval); in 2013
• Proprotein Convertase Subtilisin Kexin Type 9 (PCSK9) Inhibitors: 2 new drugs; in 2015

Note that in addition to these 19 new drug approvals, there have been 2 combination product approvals involving previously approved drugs, i.e., the cholesterol absorption inhibitor ezetimide and an HMG-CoA Reductase Inhibitor, simvastatin (Vytorin, 2004) or atorvastatin (Liptruzet, in 2013).

Comments

There has been a steady progress in the introduction of new lipid lowering drugs from the approval of the first fibrate, Atromid-S, to the very recent approval of the 2 PCSK9 inhibitors, Praluent and Repatha. Clearly the most noteworthy and successful pharmacologic class has been the HMG-CoA reductase inhibitors or statins. Other highlights are as follows:

• As mentioned above, the lipid lowering effect of niacin was first reported in 1955
• Up until the approval of the first HMG-CoA Inhibitor Mevacor in 1987, there were only 2 fibrates, Atromid-S and Lopid, and 2 bile acid sequestrants, Questran and Colestid
• There have been a total of 8 approvals of statins, starting with Mevacor in 1987 and ending with Livalo in 2009; this was over almost 22 years. Note that 1 of the statins, Baycol, was discontinued due to adverse effects
• Note that 2 of these 19 lipid lowering drugs, Juxtapid and Kynamro, were approved as orphan drugs for homozygous familial hypercholesterolemia
• This year, 2015, there already have been 2 approvals involving a new exciting mechanism, Praluent and Repatha
• It is noteworthy that registration interest for 3 of the pharmacologic classes, i.e., fibrates, bile acid sequestrants, and statins, has lasted almost 27, 27, and 22 years, respectively
• It is also noteworthy that this therapeutic class has seen a few combination products of previously approved drugs, as noted above

List of Proprietary and Established Names for Approved Lipid Lowering Drugs

For a list of proprietary and established names for these approved lipid lowering drugs, including approval dates, refer to the attached table.

Refer to page 9 of Progression of Modern Therapeutics (2014 Report) available under Reports on this website; this report also includes the methodology used.