MyFatDog        

Most drugs under development are dincontinued before they reach phase III.   The MyFatDog Pile is a list of drugs that were discontinued for one reason or another.  Sometimes these drugs had harmful side effects that weren't discovered until the later stages of development - sometimes they were discontinued for other reasons - and sometimes they can come back into development.  Atorvastatin (Lipitor) was stalled a few times during its development but ultimately was approved and marketed to become one of the best selling drugs of all time.

APL180  (Novartis).  Appeared to be an apoA-I mimetic peptide.  Reason for apparent discontinuation unknown.

APP018 (D4F)  (Novartis). An apoA-I mimetic peptide originally developed as a treatment to increase HDL levels.  Reason for apparent discontinuation unknown.

avasimibe (Pfizer).  ACAT Inhibitor.  No effect on reducing cardiovascular risk.

AVE5530 (Sanofi-Aventis).  Cholesterol absorption inhibitor.  Discontinued due to "insufficient efficacy".

AZD4121 (AstraZeneca).  Cholesterol absorption inhibitor.  Reason for discontinuation unknown.

cerivastatin (Bayer). Statin.  High rate of complications from muscle weakness.

CSL-111 (CSL Limited).  A reconstituted HDL.  Although promising, showed some liver effects and lack of efficacy when comapred to placebo.  Being reformulated as CSL112. 

CER-002  (Cerenis Therapeutics).  PPAR delta activator. Reason for apparent discontinuation unknown.

CP-800,569  (Pfizer).  Cholesteryl ester transfer protein inhibitor (CETP inhibitor). Reason for apparent discontinuation unknown although this may be a strategic move since Pfizer decided to exit the cardiovascular drug market.  This compound has been reported to have no effect on blood pressure.   

CRD-5 (Liponex prior to being acquired by ImaSight).  CRD-5 was a phospholipid supplement that is beind developed as a treatment to increase HDL levels.  Apparently discontinued.

DRF-10945 (Perlecan Pharma).  A non-fibrate PPAR alpha activator . Reason for apparent discontinuation unknown.

ETC-276 (Esperion).  Recombinant pro-apoA-I.  Limited patent life and difficulties in large-scale production.

ET-642 (Pfizer).  Synthetic HDL containing an apoA-I mimetic peptide. 

FM-VP4 (Forbes Medi-Tech).  Cholesterol absorption inhibitor. Reason for apparent discontinuation unknown.

FXR-450 (Wyeth).  FXR activator.  Reason for apparent discontinuation unknown.

implitapide (Bayer). MTP Inhibitor.  Increased amount of fat in liver. Currently licensed by Aegerion as a potential treatment for hepatitis C.

lapaquistat (TAK-475) (Takeda Pharmaceuticals).  Lapaquistat is a squalene synthase inhibitor that was being developed as a treatment to lower LDL levels.  Discontinued based on clinical data that indicated that the drug was not better that other drugs that lower LDL in both terms of effectiveness and safety.

LCAT activator  (Amgen).  The unnamed LCAT activator increased the conversion of free cholesterol to cholesteryl ester in HDL.  This drug was being developed as a treatment to increase HDL levels.

LG842  (Lexicon Pharmaceuticals and Genentech) LG842 was an antibody that bound to a protein (angiopoietin-like 4 or Angptl4) that interferes with triglyceride clearance from plasma.  Apparently discontinued during discovery phase.

LG843 (Lexicon Pharmaceuticals and Genentech)  LG843 was an antibody that bound to an undisclosed protein that regulates plasma triglyceride and cholesterol levels.  Apparently discontinued during discovery phase.

LSI-518P (Lipid Sciences).  LSI-518P was an apoA-I mimetic peptide that is being developed as a treatment to increase HDL levels. The company went bankrupt in October 2008.

LXR-623 (Karo Bio and Wyeth) LXR-623 is a liver x receptor (LXR) activator.  LXR activators are developed to increase HDL cholesterol levels but have also been shown to increase plasma triglyceride levels.  LXR-623 was reported to improve markers relating to atehrosclerosis but also had other (undislosed) effects that resulted in its discontinuation.

MDR-04227  (MDRNA).  An oliglonucleotide that interferes with the production of apolipoprotein B in liver and intestine leading to lower levels of these atherogenic lipoproteins in blood.  The company anticipated filing a new drug application in late 2009 but the drug is no longer listed in the company pipeline.

MK-1903 (Co-developed by Merck and Arena Pharmaceuticals).  A niacin receptor activator.  Did not work as expected.  No reported safety issues.

muraglitizar (Bristol-Myers Squibb/Merck). Dual PPAR alpha/gamma agonist.  Increased cardiovascular risk.

PDS-2 (Lipid Sciences).  PSD-2 was a HDL delipidation technique designed to increase the amount of pre-beta HDL in plasma and stimulate cholesterol removal from tissues (reverse cholesterol transport).  The company went bankrupt in October 2008.

PF-3,185,043  (Pfizer).  Cholesteryl ester transfer protein inhibitor (CETP inhibitor). Reason for apparent discontinuation unknown although this may be a strategic move since Pfizer decided to exit the cardiovascular drug market.  This compound has been reported to have no effect on blood pressure but was reported to be structurally similar to torcetrapib which did increase blood pressure and mortality in a clinical study.  

PLX204/PPM-204 Co-developed by Wyeth and Plexxikon.   PLX204/PPM-204 is a pan PPAR alpha/gamma/delta activator.  The drug was being developed as a treatment designed to decrease triglyceride levels and increase HDL levels. A study testing the effect of the drug on blood glucose levels and safety was terminated early since it did not meet predetermined criteria in an interim analysis.  Although still listed on the Plexxikon website, the website also mentions that Wyeth discontinued development of the compound.

probucol (available in Canada, Japan).  Antioxidant.  Lowered HDL cholesterol and rarely induced an irregular heartbeat.

R7232 (Roche).  Cholesteryl ester transfer protein inhibitor.  Discontinued due to progress with their lead compound, dalcetrapib.

torcetrapib (Pfizer). CETP Inhibitor.  Increased cardiovascuar risk.