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.
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- HMG-CoA Reductase Inhibitors, or Statins: 8 new drugs (one withdrawn from the market); over 21 years & 11 months; between 1987 and 2009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).
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.