Claim: Experimental Drug Raises Good Cholesterol Levels in Early Trial
Verdict: SUPPORTS

Retrieved passages:
title: PCSK9
text: first to market a PCSK9 inhibitor, with a competitor Amgen reaching market slightly later. The drugs are approved by the FDA for treatment of hypercholesterolemia, notably the genetic condition heterozygous familial hypercholesterolemia which causes high cholesterol levels and heart attacks at a young age. An FDA warning in March 2014 about possible cognitive adverse effects of PCSK9 inhibition caused concern, as the FDA asked companies to include neurocognitive testing into their Phase III clinical trials. A number of monoclonal antibodies that bind to and inhibit PCSK9 near the catalytic domain were in clinical trials . These include evolocumab (Amgen), bococizumab

title: AIM-HIGH trial
text: stopped early because there was a demonstrable lack of efficacy for this intervention. The addition of high dose, extended release niacin to a statin did increase HDL cholesterol, as expected, but did not reduce cardiovascular events. The analysis also showed that there was little to no probability that adding high-dose, extended release niacin to statin treatment would show a benefit even if the study continued to its originally planned completion. AIM-HIGH trial AIM-HIGH was a multi-center clinical trial related to the prophylactic treatment coronary artery disease involving some 90 sites in the United States and Canada, which was conducted between

title: Alirocumab
text: lowering of LDL cholesterol when diet and statin treatment have not worked. This was the first approval of a PCSK9 inhibitor. The FDA approval was contingent on the completion of further clinical trials to better determine efficacy and safety. Regeneron and Amgen had each filed for patent protection on their monoclonal antibodies and the companies ended up in patent litigation in the U.S. In March 2016 a district court found that alirocumab infringed Amgen's patents; Amgen then requested an injunction barring Regeneron and Sanofi from marketing alirocumab, which was granted in January 2017. The judge gave Regeneron and Sanofi 30

title: Steven Nissen
text: RECORD clinical trial (a six-year, open label randomized control trial), which failed to show heart infarct risks associated with the drug. In 2003 Nissen led a "Journal of the American Medical Association" study, producing evidence that five weekly infusions of ApoA-I Milano/phospholipids complex, a synthetic form of HDL, can possibly remove significant amounts of plaque from coronary arteries. The lipoprotein enhanced the ability of HDL, or “good” cholesterol to usher fat out of the arteries and into the liver for excretion leading to the purchase of Esperion Therapeutics, the tiny company that had produced recombinant Apo-A1 Milano, by Pfizer for

title: Atherosclerosis
text: in "JAMA" in early 2006. Ongoing work starting in the 1990s may lead to human clinical trials—probably by about 2008. These may use synthesized Apo-A1 Milano HDL directly, or they may use gene-transfer methods to pass the ability to synthesize the Apo-A1 Milano HDLipoprotein. Methods to increase high-density lipoprotein (HDL) particle concentrations, which in some animal studies largely reverses and remove atheromas, are being developed and researched. However, increasing HDL by any means is not necessarily helpful. For example, the drug torcetrapib is the most effective agent currently known for raising HDL (by up to 60%). However, in clinical trials

title: Bad Pharma
text: one drug company. Aside from all this, for several of the most important and enduring problems in medicine, we have no idea what the best treatment is, because it's not in anyone's financial interest to conduct any trials at all. In "Missing Data," Goldacre argues that the clinical trials undertaken by drug companies routinely reach conclusions favourable to the company. For example, in a 2007 journal article published in PLOS Medicine, researchers studied every published trial on statins, drugs prescribed to reduce cholesterol levels. In the 192 trials they looked at, industry-funded trials were 20 times more likely to produce

title: Pitavastatin
text: Kowa Pharmaceuticals is the owner of the American patent to pitavastatin. Like the other statins, pitavastatin is indicated for hypercholesterolaemia (elevated cholesterol) and for the prevention of cardiovascular disease. A 2009 study of the 104 week LIVES trial found pitavastatin increased HDL cholesterol, especially in patients with HDL lower than 40 mg/dL, who had a 24.6% rise, in addition to greatly reducing LDL cholesterol 31.3%. HDL improved in patients who switched from other statins and rose over time. In the 70-month CIRCLE observational study, pitavastatin increased HDL more than atorvastatin. It has neutral or possibly beneficial effects on glucose control.

title: Atorvastatin
text: and his bosses, Roger Newton and Ronald Cresswell, in 1985 convinced company executives to move the compound into expensive clinical trials. Early results comparing atorvastatin vs. simvastatin demonstrated that atorvastatin was significantly more potent and displayed fewer side effects. In 1994 the findings of a Merck-funded study were published in "The Lancet" concluding the efficacy of statins in lowering cholesterol in 4444 Scandinavian patients proving for the first time not only that a "statin reduced 'bad' LDL cholesterol but also that it led to a sharp drop in fatal heart attacks among patients with heart disease." In 1996 Warner-Lambert entered

title: Ezetimibe/simvastatin
text: small and unique patient population, 720 patients in an Amsterdam hospital with heterozygous familial hypercholesterolemia. Merck and Schering Plough have reported that they have three trials underway to focus on outcomes, measuring the drug's effect on heart attacks and strokes in patients. These results were presented in full at the American College of Cardiology meeting on 30 March 2008, two years after the last patient completed the study. The House Committee on Energy and Commerce conducted an inquiry into the delayed disclosure of the study data. In the United States, Vytorin featured a television advertising campaign showing a series of

title: Dalcetrapib
text: Dalcetrapib Dalcetrapib (INN, codenamed JTT-705) is a CETP inhibitor which was being developed by Hoffmann–La Roche until May 2012. The drug was aimed at raising the blood levels of "good cholesterol" (cholesterol carried in HDL particles, "aka" HDL-C). Prevailing observations indicate that high HDL levels correlate with better overall cardiovascular health, though it remains unclear whether raising HDL levels consequently leads to an increase in cardiovascular health. A 24-week clinical trial showed that dalcetrapib did increase HDL-C levels, supporting the agent's desired effect. Further, the dal-PLAQUE phase IIb trial found evidence of plaque reduction. Plaque reduction is an anticipated observation

title: Henry Buchwald
text: heart disease. The POSCH trials demonstrated conclusively that lowering cholesterol can reduce heart disease and resultant heart attacks and, therefore, increase life expectancy. The results from all phases of the POSCH study have contributed significant insights and long-term data related to cholesterol, heart disease, and smoking. Buchwald has received seven additional NIH research grants. Buchwald, who has a joint appointment at the University of Minnesota in Biomedical Engineering, holds 17 patents for medical devices. These include the world's first infusion port, peritoneovenous shunts, and specialty vascular catheters. He also invented the first implantable infusion pump, a precursor to implantable infusion

title: Cholesterol
text: There are several international guidelines on the treatment of hypercholesterolaemia. Multiple human trials using HMG-CoA reductase inhibitors, known as statins, have repeatedly confirmed that changing lipoprotein transport patterns from unhealthy to healthier patterns significantly lowers cardiovascular disease event rates, even for people with cholesterol values currently considered low for adults. Studies have also found that statins reduce atheroma progression. As a result, people with a history of cardiovascular disease may derive benefit from statins irrespective of their cholesterol levels (total cholesterol below 5.0 mmol/L [193 mg/dL]), and in men without cardiovascular disease, there is benefit from lowering abnormally high cholesterol

title: Ezetimibe/atorvastatin
text: Ezetimibe/atorvastatin Ezetimibe/atorvastatin (brand name Liptruzet) is a cholesterol lowering combination drug. In the United States, it was approved in May 2013 by the Food and Drug Administration for the treatment of elevated low-density lipoprotein (LDL) in patients with primary or mixed hyperlipidemia as adjunctive therapy to diet. Liptruzet has also been approved to reduce elevated total cholesterol and elevated LDL in patients diagnosed with homozygous familial hypercholesterolemia as an adjunctive treatment to other hyperlipidemia treatments. Some cardiologists opposed the approval, because the combination reduced LDL cholesterol in a clinical trial, but it did not reduce heart disease. A clinical trial

title: Colesevelam
text: reductase inhibitor (known more commonly as a statin) can further lower cholesterol levels. In controlled clinical studies involving approximately 1,400 patients, the following adverse reactions have been reported in patients treated with colesevelam. When reporting to the very common (≥ 1 / 10), common (≥ 1 / 100, 51/10), uncommon (≥ 1 / 1000, 51/100), rare (≥ 1/10.000, 51/1000) and distinction very rarely (51/10.000), including individual cases: The background incidence of flatulence and diarrhea was in patients in the same controlled clinical trials, the placebo were higher. Only constipation and dyspepsia were shown to occur in a higher percentage of

title: PCSK9
text: circulating LDL particle concentrations. Since LDL particle concentrations are thought by many experts to be a driver of cardiovascular disease like heart attacks, it is plausible that these drugs may also reduce the risk of such diseases. Clinical studies, including phase III clinical trials, are now underway to describe the effect of PCSK9 inhibition on cardiovascular disease, and the safety and efficacy profile of the drugs. Among those inhibitors under development in December 2013 were the antibodies alirocumab, evolocumab, 1D05-IgG2 (Merck), RG-7652 and LY3015014, as well as the RNAi therapeutic inclisiran. PCSK9 inhibitors are promising therapeutics for the treatment of

title: Number needed to treat
text: common (an anticoagulant to prevent heart attack for example), a prospective study may be used. A study which starts with all healthy participants is termed a prospective study, and is in contrast to a retrospective study, in which some participants already have the condition in question. Prospective studies produce much higher quality evidence, but are much more difficult and time-consuming to perform. In the table below: ASCOT-LLA manufacturer-sponsored study addressed the benefit of atorvastatin 10 mg (a cholesterol-lowering drug) in patients with hypertension (high blood pressure) but no previous cardiovascular disease (primary prevention). The trial ran for 3.3 years, and

title: Discovery and development of statins
text: trials showed very good inhibitory effect as in clinical trials, however in a long term toxicity study in dogs it resulted in toxic effects at higher doses and as a result was believed to be too toxic to be given to humans. In 1978, Alfred Alberts and colleagues at Merck Research Laboratories discovered a new natural product in a fermentation broth of "Aspergillus terreus", their product showed good HMGR inhibition and they named the product mevinolin, which later became known as lovastatin. The cholesterol controversy began in the early promotion of statins. Statins are a competitive antagonists of HMG CoA,

title: Familial hypercholesterolemia
text: since birth, probably increasing their relative risk. Prior to the introduction of the statins, clofibrate (an older fibrate that often caused gallstones), probucol (especially in large xanthomas) and thyroxine were used to reduce LDL cholesterol levels. More controversial is the addition of ezetimibe, which inhibits cholesterol absorption in the gut. While it reduces LDL cholesterol, it does not appear to improve a marker of atherosclerosis called the intima-media thickness. Whether this means that ezetimibe is of no overall benefit in FH is unknown. There are no interventional studies that directly show mortality benefit of cholesterol lowering in FH. Rather, evidence

title: Lovastatin
text: natural products with a powerful inhibitory effect on HMG-CoA reductase, were discovered in the 1970s, and taken into clinical development as potential drugs for lowering LDL cholesterol. In 1982, some small-scale clinical investigations of lovastatin, a polyketide-derived natural product isolated from "Aspergillus terreus", in very high-risk patients were undertaken, in which dramatic reductions in LDL cholesterol were observed, with very few adverse effects. After the additional animal safety studies with lovastatin revealed no toxicity of the type thought to be associated with compactin, clinical studies continued. Large-scale trials confirmed the effectiveness of lovastatin. Observed tolerability continued to be excellent, and

title: Torcetrapib
text: and atorvastatin versus taking atorvastatin alone. Pfizer recommended that all patients stop taking the drug immediately. Six studies were terminated early. One of the completed studies found it raised systolic blood pressure and concluded "Torcetrapib showed no clinical benefit in this or other studies, and will not be developed further." The drug cost $800m+ to bring into Phase III development. Dietary cholesterol needs be esterified in order to be absorbed from the gut. The enzyme, cholesterylester transfer protein (CETP), then completes the absorption of cholesterol. Drugs that interfere with the action of these peptides would aid in lowering cholesterol levels