MyFatDog
Discontinued Drugs:
Most drugs under development are discontinued 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.
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.
APA-01 (Phosphagenics). APA-01 was an anti-inflammatory drug to be used in combination
with statins to lower LDL levels and reduce inflammation. Reason for apparent discontinuation
unknown.
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.
CER-002 (Cerenis Therapeutics). PPAR delta activator. Reason for apparent discontinuation
unknow
cerivastatin (Bayer). Statin. High rate of complications from muscle weakness.
Certriad (Crestor + Trilipix) (Co-developed by AstraZeneca and Abbott). Statin and fenofibric
acid. Following response by FDA the decision was made that development was not commercially
attractive.
CSL-111 (CSL Limited). Reconstituted HDL. Although promising, showed some liver effects
and lack of efficacy when compared to placebo, probably due to excipients. Reformulated as
CSL112.
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
developed as a treatment to increase HDL levels. Apparently discontinued to due lack of efficacy.
DRF-10945 (Perlecan Pharma). A non-fibrate PPAR alpha activator . Reason for apparent
discontinuation unknown.
eprotirome (KB2115) Being developed by Karo Bio. Eprotirome was a thyroid receptor beta
activator developed as an add-on to conventional treatment. Discontinued due to toxic effects
on cartilage in dogs after 12 months treatment.
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. Reason for apparent
discontinuation unknown.
FM-VP4 (Forbes Medi-Tech). Cholesterol absorption inhibitor. Reason for apparent
discontinuation unknown.
FXR-450 (Wyeth). FXR activator. Reason for apparent discontinuation unknown.
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 atherosclerosis but
also had other (undislosed) effects that resulted in its discontinuation.
MB07811 (Metabasis prior to being acquired by Ligand). MB07811 was a thyroid receptor beta
activator. Higher doses of the drug were associated with mild increases in liver enzymes and
shifts in thyroid hormone levels. Ligand has reported that they are working on developing
second generation thyroid receptor beta activators.
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.
PPD 10558 Developed by Furiex. PPD 10558 was a novel statin that was being developed to
prevent muscle-associated side effects by targeting exposure to liver. A phase II study showed
no difference in muscle side effects despite significant LDL lowering.
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 as being under
development, Wyeth discontinued development of the compound.
pravastatin/fenofibrate (PravaFen) Developed by Shionogi & Co. This is a combination of
two approved lipid-altering medications. Appears to have been discontinued for strategic
reasons.
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.
Sobetirome (QRX-431) (QuatRx). Thyroid receptor beta activator. Reason for apparent
discontinuation unknown.
torcetrapib (Pfizer). CETP Inhibitor. Drug increased risk of cardiovascular event.
with statins to lower LDL levels and reduce inflammation. Reason for apparent discontinuation
unknown.
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.
CER-002 (Cerenis Therapeutics). PPAR delta activator. Reason for apparent discontinuation
unknow
cerivastatin (Bayer). Statin. High rate of complications from muscle weakness.
Certriad (Crestor + Trilipix) (Co-developed by AstraZeneca and Abbott). Statin and fenofibric
acid. Following response by FDA the decision was made that development was not commercially
attractive.
CSL-111 (CSL Limited). Reconstituted HDL. Although promising, showed some liver effects
and lack of efficacy when compared to placebo, probably due to excipients. Reformulated as
CSL112.
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
developed as a treatment to increase HDL levels. Apparently discontinued to due lack of efficacy.
DRF-10945 (Perlecan Pharma). A non-fibrate PPAR alpha activator . Reason for apparent
discontinuation unknown.
eprotirome (KB2115) Being developed by Karo Bio. Eprotirome was a thyroid receptor beta
activator developed as an add-on to conventional treatment. Discontinued due to toxic effects
on cartilage in dogs after 12 months treatment.
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. Reason for apparent
discontinuation unknown.
FM-VP4 (Forbes Medi-Tech). Cholesterol absorption inhibitor. Reason for apparent
discontinuation unknown.
FXR-450 (Wyeth). FXR activator. Reason for apparent discontinuation unknown.
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 atherosclerosis but
also had other (undislosed) effects that resulted in its discontinuation.
MB07811 (Metabasis prior to being acquired by Ligand). MB07811 was a thyroid receptor beta
activator. Higher doses of the drug were associated with mild increases in liver enzymes and
shifts in thyroid hormone levels. Ligand has reported that they are working on developing
second generation thyroid receptor beta activators.
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.
PPD 10558 Developed by Furiex. PPD 10558 was a novel statin that was being developed to
prevent muscle-associated side effects by targeting exposure to liver. A phase II study showed
no difference in muscle side effects despite significant LDL lowering.
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 as being under
development, Wyeth discontinued development of the compound.
pravastatin/fenofibrate (PravaFen) Developed by Shionogi & Co. This is a combination of
two approved lipid-altering medications. Appears to have been discontinued for strategic
reasons.
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.
Sobetirome (QRX-431) (QuatRx). Thyroid receptor beta activator. Reason for apparent
discontinuation unknown.
torcetrapib (Pfizer). CETP Inhibitor. Drug increased risk of cardiovascular event.
Copyright © 2008-2012 John Millar. All rights reserved.
