By: Nityanand C, Data Analyst, Aissel Solutions
Anacetrapib, Merck’s cholesteryl ester transfer protein (CETP) inhibitor has dissolved the cloud covered over the CETP inhibition concept due to a major failure of first ever CETP inhibitor Pfizer’s Torcetrapib. Dr. Christopher P. Cannon, Senior Investigator of the TIMI Study Group presented its Phase III clinical trial results at the scientific sessions of American Heart Association which made healthcare professionals across the globe to reconsider their opinion about CETP inhibition concept. Merck has planned to take forward its promising candidate into larger clinical trial which decides the future of this new era of anti-cholesterol drug concept.
Anacetrapib, Merck’s cholesteryl ester transfer protein (CETP) inhibitor has dissolved the cloud covered over the CETP inhibition concept due to a major failure of first ever CETP inhibitor Pfizer’s Torcetrapib. Dr. Christopher P. Cannon, Senior Investigator of the TIMI Study Group presented its Phase III clinical trial results at the scientific sessions of American Heart Association which made healthcare professionals across the globe to reconsider their opinion about CETP inhibition concept. Merck has planned to take forward its promising candidate into larger clinical trial which decides the future of this new era of anti-cholesterol drug concept.
Atherosclerosis, also known as arteriosclerotic vascular disease is a syndrome which majorly affects the arterial blood vessels. This is a chronic inflammatory response usually observed in the arteries due to accumulation of Low Density Lipoproteins (LDL) on the arterial walls without adequate removal of fats and cholesterol by active High Density Lipoproteins (HDL). This gradually leads to formation of atheromatous plaque on the arterial walls, making them narrow and hard.
High Density Lipoprotein particles remove cholesterol from atheromatous plaque within the arteries and transport it back to the liver for excretion or re-utilization but LDL particles drop bits of it on the arterial walls. Gradually, these bits accumulate together with other microscopic debris and lead to hardening of arteries. Hence maintaining a fine balance of HDL and LDL levels in the blood is important to reduce the risk of Atherosclerosis.
Anti-Cholesterol drugs have been the major target of Pharmaceutical Industries since decades. Statins, a class of drugs which lower cholesterol levels by inhibiting the cholesterol producing enzyme HMG-CoA reductase dominated the anti-cholesterol drug market. Especially Pfizer’s Liptor (atorvastatin) became the best-selling drug in pharma history with more than $10 billion sales by 2009 (As reported in article dated 11-Jan-2011 by Genetic Engineering and Biotechnology News). Thus Pfizer has completely dominated cardiovascular drug market, specially statin market in 2009-10. However by the end of 2010 different branded statins by leading pharmaceutical giants had hit the market. But the potential of anti-cholesterol drugs made the pharmaceutical industries to search for a new era of cholesterol treatment.
CETP inhibitor, which inhibits transfer of cholesterol from HDL to LDL by CETP transferase enzyme, took birth by the drive of pharmaceuticals to leverage the potential in the anti-cholesterol drug market. But there was a cloud over the potential of CETP inhibition concept when one of the CETP inhibitors, Pfizer’s torcetrapib faced a major clinical failure in Phase III trial. The firm which witnessed a biggest success in the anti-cholesterol drug (Statins) market in 2009-10 happened to face one of the biggest flops in pharma history.
At the scientific sessions of American Heart Association in November 2010 Merck once again drew the attention of cardiology experts, when Dr. Christopher P. Cannon, Senior Investigator of the TIMI Study Group in the cardiovascular division of Brigham and Women’s Hospital in Boston, MA presented the results of Phase III DEFINE (Determining the EFficacy and Tolerability of CETP INhibition with AnacEtrapib) trial. The trail included more than 1600 patients with coronary heart disease or coronary risk equivalent and spanned over 18 months. According to the results anacetrapib has met its endpoints, safety and efficacy. It was able to lower the LDL-cholesterol levels after 24 weeks of treatment without causing any adverse effects such as change in blood pressure, change in aldosterone level etc. The researchers also reported that it was able to decrease LDL-cholesterol level by 40% and increase HDL-cholesterol by 138% [2] in patients already treated with statin and cardiovascular events occurred only in 16 anacetrapib treated patients whereas the occurrence was observed in 21 placebo treated patients.
Merck has planned to move forward with another large group trail “The REVEAL (Randomized EValuation of the Effects of Anacetrapib through Lipid-modification)” by April 2011 spanning over 6 years, involving 30000 [3] men and women aged at least 50 with a history of heart attack, stroke or peripheral arterial disease. This trial will be co-investigated by Dr. Martin Landray and Dr. Louise Bowman of Oxford University. According to them the trial will majorly look at whether the cholesterol level changes can really prevent coronary deaths and heart attacks and if the impressive effects of anacetrapib on cholesterol levels are translated into fewer deaths and heart attacks, then Anacetrapib treatment has the potential to produce substantial benefit for patients.
However a recent study carried out by Dr. Daniel Rader, Director of Preventive Cardiovascular Medicine at the University of Pennsylvania School of Medicine in Philadelphia and others, concluded that it is the expulsion capacity of HDL which influences the reduction of arteriosclerotic vascular disease risk than the quantity of it in blood.[4] This conclusion definitely influences the huge research undertaking on Anacetrapib as till date none of the study has been reported about the quality of HDL levels that is being increased in subjects treated with Anacetrapib.
May be not very soon but definitely, if Anacetrapib meets all the endpoints in the upcoming clinical trial as well, then people at a risk of being victims of Coronary Heart Disease and who have already been victims of it will have a life line in the pharmacy shelves by 2017.
[1] American Heart Journal; Vol. 157(2); Feb 2009
[2] New England Journal of Medicine; Vol. 365(25); Dec 2010
[3] University of Oxford News Release; Nov 2010
[4] New England Journal of Medicine; Vol. 364(2); Jan 2011
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