The highest dose of AstraZeneca’s small molecule halved levels of a type of “bad” cholesterol after 12 weeks, hitting the goal of a phase 2 trial in patients with a lipid disorder.
The candidate in question, dubbed AZD0780, is an oral small molecule PCSK9 inhibitor in development for dyslipidemia, a condition characterized by elevated cholesterol in the blood that can progress to clogged arteries, known as atherosclerosis.
AstraZeneca used the American College of Cardiology conference today to unveil data from a phase 2 study of 428 patients with the condition who received one of four doses of AZD0780 or placebo, along with standard-of-care statin therapy and, in some cases, the approved high cholesterol drug ezetimibe.
The highest daily dose, 30 mg, of AZD0780 was tied to a 50.7% reduction in low-density lipoprotein cholesterol (LDL-C) at 12 weeks. Around this level of efficacy was observed regardless of whether patients were also receiving moderate or high-intensity statin doses alongside AZD0780, AstraZeneca noted.
A total of 84% of patients who received the 30 mg dose were able to meet the American Heart Association guidelines of having LDL-C levels under 79 mg/dL, compared to 13% of those on placebo.
The rate of adverse events in the combined AZD0780 treatment groups was 38.2%, compared to 32.6% in the placebo cohort. The frequency of treatment discontinuations due to these events was 1.5% for the investigational arm and 2.3% for placebo.
“These new data reflect AZD0780’s ability to reduce LDL-cholesterol in patients who need more options to manage their cholesterol and related risks when standard of care therapy is not enough,” Sharon Barr, AstraZeneca's executive vice president of biopharmaceuticals R&D, said in a release.
“As a novel small molecule oral PCSK9 inhibitor that can be taken without fasting restrictions, AZD0780 has the potential to be a game changer that could offer LDL-C lowering with greater convenience for patients,” Barr added.
The phase 2 results echo an early-stage readout for AZD0780 last year that showed a similar 52% reduction in LDL-C.
The hypercholesterolemia market is currently dominated by injectable PCSK9 inhibitors in the form of Amgen’s Repatha and Sanofi-Regeneron’s Praluent. Meanwhile, Novartis’ Leqvio uses small-interfering RNA technology to decrease PCSK9 production in the liver.
AstraZeneca’s attempt to get an oral option to patients in the form of AZD0780 remains behind Merck & Co.’s own oral PCSK9 inhibitor MK-0616, which is already undergoing a slate of phase 3 trials to confirm its LDL-C-lowering capabilities.
In today’s release, Michael Koren, M.D., CEO and medical director of the Jacksonville Center for Clinical Research in Florida, said the results for AZD0780 are “particularly important because the majority of patients with atherosclerotic disease today do not reach their LDL-C goals, despite availability of lipid-lowering therapies such as statins and injectable PCSK9 inhibitors.”