MyFatDog        

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.  Phase III studies started in December 2009 with completion expected in December 2011.

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 rthe 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, diziness, nausea anxiety, and reversible hair growth on the forehead, back, arms and legs.

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.  Plans are to seek approval in Europe in 2011 prior to filing for approval in Canada and the US.

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 studies are scheduled for completion in 2010 and 2011.  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.

mipomersen (ISIS 301012)  Currently being co-developed by ISIS Phamaceuticals and Genzyme.  Mipomersen 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.  A safety study, expected to be completed in 2010, will determine the extent of fat accumulation in liver, a potential side effect, in various patient groups.  Studies are also being 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.  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 may hve been associated with an increase in liver fat.  There was no evidence of any liver disease.

pravastatin/fenofibrate (PravaFen) Being developed by Shionogi & Co.  This is a combination of two approved lipid-altering medications.  This is being developed as a treatment for mixed dyslipidemia (high triglycerides, high LDL and low HDL).  A new drug application was submitted to the US FDA in November of 2009. The company anticipates a product launch in 2010.  Side effects: Side effects of pravastatin include stomach pain, nausea, diarrhea, fatigue, headache, nasal passage infection, skin rash, generalized pain.  Side effects of fenofibrate include abnormal liver function tests.

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 primiarily as an anti-diabetes drug .  A study testing the abilty of the drug to improve diabetes has recently been completed and showed that aleglitazar is effective in lowering LDL and triglcyrides and can also increase HDL levels.  The drug does casue a significant increase in creatinine which could be casue for concern.  A phase III study testing the benefit of treatment with aleglitazar in patients with acute coronary syndrome and type 2 diabetes is scheduled to begin in March 2010.

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 cardiovasular 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).

Tredaptive (extended-release niacin/laropiprant) Formerly known as "Cordaptive".  Being developed by Merck.  Tredaptive is a combination of extended-release niacin and laropiprant, a prostaglandin D2 receptor antagonist.  The combination drug is designed to increase HDL and reduce triglyceride levels (from niacin) while minimizing the subcutaneous flushing and itching (laropiprant) that is frequently associated with niacin.  The drug is currently approved in Europe.  There is a large study (with a target enrollment of 20,000 patients) designed to see if the drug can prevent cardiovascular events (heart attack, stroke, etc) in patients with a history of circulatory problems.  The study is expected to be completed in January 2013.  Side effects: Include diarrhea, "pins and needles" feeling, itching and skin flushing (redness), nausea and vomiting.  Patient information can be found in this link in the UK where the drug is approved for use.

varespladib (A-002)  Being developed by Anthera Pharmaceuticals.  Varespladib is a secretory phospholipase A2 (sPLA2) inhibitor that is being developed as an 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 is scheduled for completion in February 2012.

Phase III – 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.