Enlicitide chloride

AstraZeneca is significantly trailing Merck & Co. in the hypercholesterolaemia space. AstraZeneca’s small molecule lowered levels of “bad” cholesterol by more than half in patients who had never received treatment for their condition, according to results from an early-stage trial. The U.K. pharma presented the results today at the European Atherosclerosis Society in France, according to a release. AZD0780 is an oral small molecule PCSK9 inhibitor in development for dyslipidaemia, a condition characterized by elevated cholesterol in the blood that can progress to clogged arteries, also called atherosclerosis. The phase 1 trial is focused on this disease, however, an additional arm is testing the therapy in 35 patients with hypercholesterolaemia, or high cholesterol. High LDL-C, also known as "bad" cholesterol, is associated with a risk of cardiovascular disease. The main goal of the test was the safety, tolerability, pharmacokinetics and pharmacodynamics of AZD0780 in lowering LDL-C. In the hypercholesterolaemia arm presented at the conference, patients who took AZD0780 as well as a statin had a statistically significant 52% reduction in low-density lipoprotein cholesterol (LDL-C), with a 78% total reduction from baseline. The trial moved on to phase 2 in patients with dyslipidaemia earlier in the year, according to AstraZeneca. “AZD0780 inhibits PCSK9 via a novel, previously unexplored, mode of action that is compatible with traditional oral small molecule drug discovery,” said AstraZeneca’s Sharon Barr, executive vice president of biopharmaceuticals R&D, in a statement. “We are progressing development of AZD0780 as an innovative, convenient oral option for patients who are currently unable to meet their LDL-C targets with statins alone to reduce their risk of CV events.” AstraZeneca is significantly trailing Merck & Co. in the hypercholesterolaemia space. The rival’s oral PCSK9 inhibitor MK-0616 is already in three phase 3 trials to examine its ability to lower LDL-C and lower the risk of cardiovascular events. The primary completion date for the initial two studies in the trio is September 2025. The third trial is looking at cardiovascular outcomes and isn’t expected to wrap up until late 2029, after six years of watching patients. Both entrants are trying to replace Amgen’s Repatha and Sanofi-Regeneron’s Praluent, which are approved injectables for the same condition.

AstraZeneca has taken the wraps off early data for its oral PCSK9 inhibitor AZD0780, setting the stage for a potential rivalry with Merck & Co.'s similar programme, dubbed MK-0616, as the two companies race to bring the first convenient pill form of these potent cholesterol-lowering drugs to market. Findings were presented Wednesday at the annual meeting of the European Atherosclerosis Society (EAS).The Phase I study evaluated two dose levels of AZD0780, 30mg and 60mg, administered orally once daily for 28 days to separate cohorts of 15 participants each, compared to a placebo group of equal size. Separately, 35 participants with LDL levels ranging from 100 to 190mg/dL took the statin Crestor (rosuvastatin) for 3 weeks, followed by either 30mg of AZD0780 or placebo for another 4 weeks.Over 50% decline in 'bad' cholesterolResults demonstrated that AZD0780, when administered to treatment-naive hypercholesterolaemic patients after the Crestor run-in period, achieved a statistically significant 52% reduction in LDL cholesterol versus Crestor alone. The total reduction in LDL was 78% when compared to baseline levels.As monotherapy, the low and high AZD0780 doses cut cholesterol levels by 30% and 38%, respectively, versus baseline. Preliminary data also suggested that food increased total exposure by about 30% compared to fasting. No serious adverse events were reported.Advantages over current injectablesRegina Fritsche Danielson, global head of research and early development, cardiovascular, renal and metabolic diseases at AstraZeneca, underscored the advantages an effective oral PCSK9 option could hold over currently marketed monoclonal antibodies like Sanofi and Regeneron Pharmaceuticals' Praluent (alirocumab) and Amgen's Repatha (evolocumab), which are both injected."Many patients are not really open to take an injectable, and physicians are not so keen to prescribe the injectable PCSK9, so now we have an alternative and simple small tablet that we can give to these patients to really control the LDL cholesterol," Danielson told FirstWord. Achieving 50% more cholesterol lowering on top of statins could enable over 90% of patients to hit target cholesterol levels, she says, a key goal given the cardiovascular (CV) risk that persists in many people despite existing therapies.Merck's contenderWhile Merck's MK-0616 generated excitement earlier by posting around 60% LDL-cholesterol reductions at the highest dose in Phase II testing, analysts at Jefferies suggest AstraZeneca's design could prove advantageous. Unlike Merck's macrocyclic peptide, which  requires a GI absorption enhancer, "AZD0780 is a true small molecule, from a prior acquisition of Dogma Therapeutics, and so should not have meaningful food effects," they said.Merck kicked off a Phase III programme for MK-0616 last year. In addition to a pair of registrational studies to evaluate LDL-cholesterol reduction, the company launched a Phase III CV outcomes study last October, with a planned 2029 readout. See – Spotlight On: Merck & Co.'s oral PCSK9 - why it's so important.The AZD0780 data come as AstraZeneca has laid out an ambitious plan to nearly double its revenues to $80 billion by 2030. During the company's recent investor day, management hinted that AZD0780 could also be part of a combination with its next-generation oral GLP-1 agonist AZD5004. For more, see Spotlight On: AstraZeneca's bold ambitions - the key takeaways.Phase II data by year-endBut for now, the focus for AZD0780 is on curbing LDL cholesterol. AstraZeneca started a Phase II dyslipidaemia study in January that is "recruiting extremely well," according to Danielson, "so we actually are very hopeful that we will have the data towards the end of this year." The company is anticipating an end-of-Phase-II meeting when the study wraps up to discuss the Phase III design. Danielson did not want to tease any timelines for when AZD0780 could hit the market, but said that "it's a very accelerated programme."