MyFatDog
Phase III
Phase III Pipeline Drugs
AMR-101 Being developed by Amarin. AMR-101 is a purified long chain fatty acid, eicopentaenoic
acid (EPA). This is one of the omega-3 fatty acids that is found in fish oil. AMR 101 is being
developed as a treatment to reduce very high triglyceride levels. The results of the phase III
MARINE trial showed that triglyceride levels were reduced up to 45% in patients with very high
triglyceride levels without any evidence for increasing LDL cholesterol levels. The phase III
ANCHOR trial showed triglyceride lowering of up to 22% could be achieved in patients with high
triglycerides who were also under statin treatment. The company is currently conducting an
cardiovascular outcome study, REDUCE-IT (Reduction of Cardiovascular Events with EPA -
Intervention Trial), in 8,000 patients with high triglycerides who are at increased risk of
cardiovascular disease. The company has also filed a new drug application (NDA) with the US
FDA to use AMR-101 to treat patients with very high triglyceride levels.
anacetrapib (MK-859) Being developed by Merck. Anacetrapib is a cholesteryl ester transfer
protein inhibitor (CETP inhibitor) that is being developed as a treatment to increase HDL levels.
The results of the DEFINE trial showed that the drug reduced LDL by 40% in patients with
moderate baseline LDL levels that were already undergoing under treatment with statins. The
drug also increased HDL levels by 138%. Anacetrapib did not show any effect on blood pressure
which was seen in a study with a different drug in the same class. A new study, REVEAL
(Randomized EValuation of the Effects of Anacetrapib through Lipid-modification), will be
conducted at multiple worldwide sites to test if anacetrapib can reduce coronary events and heart
attacks. The study is planned to being in early 2011 and is expected to enroll 30,000 people
that will be studied over a 4 year period.
darapladib (SB-480848) Being developed by GlaxoSmithKline (GSK). Discovered using
technology developed by Human Genome Sciences. Darapladib is an inhibitor of
lipoprotein-associated phospholipase A2 (LP-PLA2 inhibitor) which is being developed as a
treatment to reduce the formation of pro-atherogenic LDL. The drug failed to achieve it's
primary endpoint in the IBIS-2 trial. Despite this there were promising results from the IBIS-2
study suggesting that the progression of atherosclerosis was halted. The STABILITY study, a
study testing the ability of the drug to prevent major adverse cardiovascular events in patients
with acute coronary syndrome, was started in December 2009 and has a target date for
completion of 2014. The study has enrolled 15,828 patients currently being treated with statins
from 477 study sites. Side effects: Include unpleasant odor in feces/urine, diarrhea, change in
taste.
DCCR Being developed by Essentialis. DCCR (diazoxide choline controlled release) is an activator
of the sulfonurea receptor 1 component of the ATP-dependent potassium channel. The drug is
being developed to lower plasma triglyceride levels in patients with very high triglycerides (greater
than 500 mg/dl). A phase III study testing the effect of the drug on lowering plasma triglyceride
levels in patients with very high triglycerides (greater than 500 mg/dl) received a Special Protocol
Assessment from the US FDA and is scheduled to begin in March 2011 with a completion date
estimated as December 2012 . Side effects: Though none are specifically available for this
proprietary version of diazoxide, information is available for orally administered diazoxide. Side
effects for generic diazoxide include headache, dizziness, nausea anxiety, and reversible hair
growth on the forehead, back, arms and legs.
Epanova Being developed by Omthera pharmaceuticals. Epanova is a proprietary mix of fish
oil-derived fatty acids EPA and DHA that is being developed for the treatment of high
triglycerides. The drug is currently being tested for its safety and effectiveness in patients with
high triglycerides who are at risk for cardiovascular disease.
Glybera (AMT-011) Being developed by Amsterdam Medical Therapeutics. Glybera is an
orphan gene therapy drug that is being developed to lower triglycerides in people with very high
triglyceride levels. Currently the target population is patients with lipoprotein lipase deficiency, a
rare disorder. The European Medicines Agency (EMA) recommended that Glybera should not be
granted marketing authorization. The reasons for the refusal (listed here) were lack of evidence
for persistent triglyceride lowering as well as lack of evidence for a reduced incidence of
pancreatitis in patients treated with Glybera. The EMA suggested that these concerns could be
addressed in further studies. A final decision regarding whether or not Glybera is approvable in
Europe should be made by May 2012.
lomitapide (AEGR-733) Being developed by Aegerion. AEGR-733 is a MTP inhibitor that is
being developed as a treatment to lower LDL levels. Studies are ongoing to measure LDL
lowering and safety in patients with homozygous familial hypercholesterolemia. The company
filed for regulatory approval in both Europe and the US for use of lomitapide for treating patients
with homozygous familial hypercholesterolemia in March 2012. Side effects: There were
dose-related side effects reported that include increase in liver enzymes and accumulation of liver
fat. A recent presentation suggested that the increase in liver fat may be temporary and may
resolve with longer treatment.
Kynamro (mipomersen; ISIS 301012) Currently being co-developed by ISIS Phamaceuticals
and Genzyme. Kynamro is an antisense oligonucleotide (ASO) to apoB (apoB antisense), the
main protein on VLDL, LDL and Lp(a). It's designed to lower VLDL, LDL and Lp(a) levels in
plasma. Studies have been conducted to test the effectiveness of the drug in lowering LDL
cholesterol in a number of patient groups that are at high risk of developing heart disease. The
company has filed an application with the European Medicines Agency (EMA) for approval to use
the drug to treat hypercholesterolemia in patients with heterozygous and homozygous familial
hypercholesteromia. A new drug application is expected to be filed with the US FDA in the first
quarter of 2012. Side effects: Injection site reaction was seen at high frequency at all doses
studied. Other effects appeared to be dose-related. These include nausea, fatigue, headache,
muscle fatigue, low white cell count, and nasal passage infection. A recent study has also
reported liver enzyme elevations in a small number of patients treated. This appears to be
associated with a substantial increase in liver fat in some patients. There was no evidence of any
liver disease.
R1439 (aleglitazar) Being developed by Roche. R1439 is a dual PPAR alpha/gamma activator
designed to lower triglyceride levels and increase HDL levels. The drug would also be expected to
improve insulin sensitivity in insulin-resistant patients and it appears that it is being developed
primarily as an anti-diabetes drug . A study testing the ability of the drug to improve diabetes
has recently been completed and showed that aleglitazar is effective in lowering LDL and
triglycerides and can also increase HDL levels. The drug does cause a significant increase in
creatinine which could be cause for concern. A phase III study testing the benefit of treatment
with aleglitazar in patients with acute coronary syndrome and type 2 diabetes began in February
2010 with results expected in 2015.
RO4607381 (R1658; JTT-705; dalcetrapib) Being developed by Roche (licensed the drug
from Japan Tobbacco). RO4607381 is a cholesteryl ester transfer protein inhibitor (CETP
inhibitor) that is being developed as a treatment to increase HDL levels. The drug has been
shown to improve the lipid profile alone and in combination with a statin. However, since there is
uncertainty about the clinical benefits of CETP inhibitors, the FDA will likely require evidence that
the drug can prevent cardiovascular events when compared to standard treatments. There is a
large study (with a target enrollment of 15,600 patients) designed to see if the drug can prevent
cardiovascular events (heart attack, stroke, etc) in patients with existing cardiovascular disease.
The study is expected to be completed in April 2013. A second study designed to measure the
progression of atherosclerosis in 900 patients with cardiovascular disease was recently
announced. Side effects: The most common side effects reported were dose related and were
not different from the placebo group. These included gastrointestinal in nature (diarrhea,
flatulence, constipation and nausea).
varespladib (A-002) Being developed by Anthera Pharmaceuticals. Varespladib is a secretory
phospholipase A2 (sPLA2) inhibitor that is being developed as an anti-inflammatory treatment to
reduce dysfunctional LDL levels. The company announced that the drug met its primary goal of
reducing LDL in patients with acute coronary syndrome (ACS). The company reached an
agreement with the FDA and will move forward with a new study, the VISTA-16 study (Vascular
Inflammation Suppression to Treat Acute Coronary Syndrome - 16 Weeks) which is designed to
test the drug in combination with a statin over a 16 week period in patients with acute coronary
syndrome. That study was recently halted due to lack of efficacy so the future of varespladib is
in question.
AMR-101 Being developed by Amarin. AMR-101 is a purified long chain fatty acid, eicopentaenoic
acid (EPA). This is one of the omega-3 fatty acids that is found in fish oil. AMR 101 is being
developed as a treatment to reduce very high triglyceride levels. The results of the phase III
MARINE trial showed that triglyceride levels were reduced up to 45% in patients with very high
triglyceride levels without any evidence for increasing LDL cholesterol levels. The phase III
ANCHOR trial showed triglyceride lowering of up to 22% could be achieved in patients with high
triglycerides who were also under statin treatment. The company is currently conducting an
cardiovascular outcome study, REDUCE-IT (Reduction of Cardiovascular Events with EPA -
Intervention Trial), in 8,000 patients with high triglycerides who are at increased risk of
cardiovascular disease. The company has also filed a new drug application (NDA) with the US
FDA to use AMR-101 to treat patients with very high triglyceride levels.
anacetrapib (MK-859) Being developed by Merck. Anacetrapib is a cholesteryl ester transfer
protein inhibitor (CETP inhibitor) that is being developed as a treatment to increase HDL levels.
The results of the DEFINE trial showed that the drug reduced LDL by 40% in patients with
moderate baseline LDL levels that were already undergoing under treatment with statins. The
drug also increased HDL levels by 138%. Anacetrapib did not show any effect on blood pressure
which was seen in a study with a different drug in the same class. A new study, REVEAL
(Randomized EValuation of the Effects of Anacetrapib through Lipid-modification), will be
conducted at multiple worldwide sites to test if anacetrapib can reduce coronary events and heart
attacks. The study is planned to being in early 2011 and is expected to enroll 30,000 people
that will be studied over a 4 year period.
darapladib (SB-480848) Being developed by GlaxoSmithKline (GSK). Discovered using
technology developed by Human Genome Sciences. Darapladib is an inhibitor of
lipoprotein-associated phospholipase A2 (LP-PLA2 inhibitor) which is being developed as a
treatment to reduce the formation of pro-atherogenic LDL. The drug failed to achieve it's
primary endpoint in the IBIS-2 trial. Despite this there were promising results from the IBIS-2
study suggesting that the progression of atherosclerosis was halted. The STABILITY study, a
study testing the ability of the drug to prevent major adverse cardiovascular events in patients
with acute coronary syndrome, was started in December 2009 and has a target date for
completion of 2014. The study has enrolled 15,828 patients currently being treated with statins
from 477 study sites. Side effects: Include unpleasant odor in feces/urine, diarrhea, change in
taste.
DCCR Being developed by Essentialis. DCCR (diazoxide choline controlled release) is an activator
of the sulfonurea receptor 1 component of the ATP-dependent potassium channel. The drug is
being developed to lower plasma triglyceride levels in patients with very high triglycerides (greater
than 500 mg/dl). A phase III study testing the effect of the drug on lowering plasma triglyceride
levels in patients with very high triglycerides (greater than 500 mg/dl) received a Special Protocol
Assessment from the US FDA and is scheduled to begin in March 2011 with a completion date
estimated as December 2012 . Side effects: Though none are specifically available for this
proprietary version of diazoxide, information is available for orally administered diazoxide. Side
effects for generic diazoxide include headache, dizziness, nausea anxiety, and reversible hair
growth on the forehead, back, arms and legs.
Epanova Being developed by Omthera pharmaceuticals. Epanova is a proprietary mix of fish
oil-derived fatty acids EPA and DHA that is being developed for the treatment of high
triglycerides. The drug is currently being tested for its safety and effectiveness in patients with
high triglycerides who are at risk for cardiovascular disease.
Glybera (AMT-011) Being developed by Amsterdam Medical Therapeutics. Glybera is an
orphan gene therapy drug that is being developed to lower triglycerides in people with very high
triglyceride levels. Currently the target population is patients with lipoprotein lipase deficiency, a
rare disorder. The European Medicines Agency (EMA) recommended that Glybera should not be
granted marketing authorization. The reasons for the refusal (listed here) were lack of evidence
for persistent triglyceride lowering as well as lack of evidence for a reduced incidence of
pancreatitis in patients treated with Glybera. The EMA suggested that these concerns could be
addressed in further studies. A final decision regarding whether or not Glybera is approvable in
Europe should be made by May 2012.
lomitapide (AEGR-733) Being developed by Aegerion. AEGR-733 is a MTP inhibitor that is
being developed as a treatment to lower LDL levels. Studies are ongoing to measure LDL
lowering and safety in patients with homozygous familial hypercholesterolemia. The company
filed for regulatory approval in both Europe and the US for use of lomitapide for treating patients
with homozygous familial hypercholesterolemia in March 2012. Side effects: There were
dose-related side effects reported that include increase in liver enzymes and accumulation of liver
fat. A recent presentation suggested that the increase in liver fat may be temporary and may
resolve with longer treatment.
Kynamro (mipomersen; ISIS 301012) Currently being co-developed by ISIS Phamaceuticals
and Genzyme. Kynamro is an antisense oligonucleotide (ASO) to apoB (apoB antisense), the
main protein on VLDL, LDL and Lp(a). It's designed to lower VLDL, LDL and Lp(a) levels in
plasma. Studies have been conducted to test the effectiveness of the drug in lowering LDL
cholesterol in a number of patient groups that are at high risk of developing heart disease. The
company has filed an application with the European Medicines Agency (EMA) for approval to use
the drug to treat hypercholesterolemia in patients with heterozygous and homozygous familial
hypercholesteromia. A new drug application is expected to be filed with the US FDA in the first
quarter of 2012. Side effects: Injection site reaction was seen at high frequency at all doses
studied. Other effects appeared to be dose-related. These include nausea, fatigue, headache,
muscle fatigue, low white cell count, and nasal passage infection. A recent study has also
reported liver enzyme elevations in a small number of patients treated. This appears to be
associated with a substantial increase in liver fat in some patients. There was no evidence of any
liver disease.
R1439 (aleglitazar) Being developed by Roche. R1439 is a dual PPAR alpha/gamma activator
designed to lower triglyceride levels and increase HDL levels. The drug would also be expected to
improve insulin sensitivity in insulin-resistant patients and it appears that it is being developed
primarily as an anti-diabetes drug . A study testing the ability of the drug to improve diabetes
has recently been completed and showed that aleglitazar is effective in lowering LDL and
triglycerides and can also increase HDL levels. The drug does cause a significant increase in
creatinine which could be cause for concern. A phase III study testing the benefit of treatment
with aleglitazar in patients with acute coronary syndrome and type 2 diabetes began in February
2010 with results expected in 2015.
RO4607381 (R1658; JTT-705; dalcetrapib) Being developed by Roche (licensed the drug
from Japan Tobbacco). RO4607381 is a cholesteryl ester transfer protein inhibitor (CETP
inhibitor) that is being developed as a treatment to increase HDL levels. The drug has been
shown to improve the lipid profile alone and in combination with a statin. However, since there is
uncertainty about the clinical benefits of CETP inhibitors, the FDA will likely require evidence that
the drug can prevent cardiovascular events when compared to standard treatments. There is a
large study (with a target enrollment of 15,600 patients) designed to see if the drug can prevent
cardiovascular events (heart attack, stroke, etc) in patients with existing cardiovascular disease.
The study is expected to be completed in April 2013. A second study designed to measure the
progression of atherosclerosis in 900 patients with cardiovascular disease was recently
announced. Side effects: The most common side effects reported were dose related and were
not different from the placebo group. These included gastrointestinal in nature (diarrhea,
flatulence, constipation and nausea).
varespladib (A-002) Being developed by Anthera Pharmaceuticals. Varespladib is a secretory
phospholipase A2 (sPLA2) inhibitor that is being developed as an anti-inflammatory treatment to
reduce dysfunctional LDL levels. The company announced that the drug met its primary goal of
reducing LDL in patients with acute coronary syndrome (ACS). The company reached an
agreement with the FDA and will move forward with a new study, the VISTA-16 study (Vascular
Inflammation Suppression to Treat Acute Coronary Syndrome - 16 Weeks) which is designed to
test the drug in combination with a statin over a 16 week period in patients with acute coronary
syndrome. That study was recently halted due to lack of efficacy so the future of varespladib is
in question.
Phase III studies involve treatment of patients with the disease or condition that the drug is
intended for and often are done in a direct head-to-head comparison with other drugs approved
to treat the condition. Phase III studies usually involve more than 500 patients and can last from
several months to several years. The objective of phase III is to demonstrate long-term safety
and clinical benefit.
If the drug gets through phase III, the data is submitted to the FDA where it is reviewed. The
FDA will make a decision as to whether the drug can be approved. The FDA may grant approval,
may request additional safety data (which can prolong the approval process by several months or
years) or may recommend against approval.
intended for and often are done in a direct head-to-head comparison with other drugs approved
to treat the condition. Phase III studies usually involve more than 500 patients and can last from
several months to several years. The objective of phase III is to demonstrate long-term safety
and clinical benefit.
If the drug gets through phase III, the data is submitted to the FDA where it is reviewed. The
FDA will make a decision as to whether the drug can be approved. The FDA may grant approval,
may request additional safety data (which can prolong the approval process by several months or
years) or may recommend against approval.
Copyright © 2008-2012 John Millar. All rights reserved.
