AstraZeneca's PCSK9 inhibitor lowers cholesterol in phase 1 trial, rivaling Merck

AstraZeneca, a major player in the pharmaceutical industry, is working diligently to catch up with Merck & Co. in the hypercholesterolaemia market. According to recent data from an early-stage trial, AstraZeneca’s investigational drug, AZD0780, has shown promising results in reducing levels of low-density lipoprotein cholesterol (LDL-C), often referred to as "bad" cholesterol, by more than half in patients who had never been treated for their condition. These findings were presented at the European Atherosclerosis Society meeting in France.

AZD0780 is an oral small molecule PCSK9 inhibitor. PCSK9 inhibitors are a class of drugs used to lower cholesterol levels in the blood. Dyslipidaemia, the broader condition targeted by AZD0780, is characterized by abnormal amounts of lipids in the blood and can lead to clogged arteries or atherosclerosis, increasing the risk of cardiovascular events.

The phase 1 trial for AZD0780 primarily focused on evaluating its safety, tolerability, pharmacokinetics, and pharmacodynamics. Additionally, an arm of the study included 35 patients suffering from hypercholesterolaemia, specifically targeting the reduction of high LDL-C levels. The trial's primary objective was to understand how effectively AZD0780 could lower LDL-C levels, a critical factor in managing cardiovascular disease risk.

Results from this specific arm of the study indicated that patients who received AZD0780 alongside a statin experienced a significant 52% reduction in LDL-C, culminating in a total 78% reduction from baseline levels. This substantial decrease highlights the potential of AZD0780 as a beneficial treatment for individuals who cannot achieve their LDL-C goals with statins alone.

Following these promising results, AZD0780 has advanced to phase 2 trials, focusing on a broader patient population with dyslipidaemia. Sharon Barr, AstraZeneca’s Executive Vice President of Biopharmaceuticals R&D, emphasized the novel mechanism of action exhibited by AZD0780. Barr stated that the drug offers a unique, previously unexplored approach compatible with traditional oral small molecule drug discovery. She highlighted the company’s commitment to developing AZD0780 as an innovative and convenient oral option, particularly for patients struggling to meet their LDL-C targets with current statin treatments.

Despite these advancements, AstraZeneca still lags behind Merck & Co. in the hypercholesterolaemia arena. Merck’s own oral PCSK9 inhibitor, MK-0616, is further along in its development journey, with three phase 3 trials underway to evaluate its efficacy in lowering LDL-C and reducing cardiovascular event risks. The initial two studies in this trio are expected to be completed by September 2025, while the third, which focuses on cardiovascular outcomes, will continue until late 2029, after six years of patient observation.

Both AstraZeneca and Merck are racing to develop effective oral treatments that could potentially replace existing injectable options like Amgen’s Repatha and Sanofi-Regeneron’s Praluent, which are currently approved for managing high cholesterol. The competitive landscape indicates a significant interest in providing patients with more accessible and convenient treatment options, leveraging the potential of oral PCSK9 inhibitors to meet the unmet needs in cholesterol management and cardiovascular risk reduction.