AstraZeneca Highlights Initial Results for Oral PCSK9 Inhibitor

AstraZeneca has unveiled promising Phase I trial results for its PCSK9 inhibitor, AZD0708, which demonstrated a considerable decrease in low-density lipoprotein cholesterol (LDL-C) among patients with elevated levels of "bad" cholesterol or hypercholesterolemia. This trial primarily focused on evaluating the safety, tolerability, and pharmacodynamics of AZD0708 in lowering LDL-C levels.

The study's findings revealed that AZD0708 could reduce LDL-C levels by 52% in patients who were also on rosuvastatin, a statin that is commonly used to lower bad cholesterol and increase good cholesterol. Additionally, in treatment-naïve patients with hypercholesterolemia, AZD0708 resulted in a 78% total reduction from baseline levels.

AstraZeneca also highlighted that preliminary data regarding dosing regimens—comparing administration with food versus fasting—indicated greater dosing flexibility when taken with food. Importantly, no serious adverse events were reported, and the treatment was well tolerated by participants.

Sharon Barr, the executive vice president of biopharmaceuticals R&D at AstraZeneca, emphasized the significance of PCSK9 in cholesterol management and pointed to the compelling data from AZD0708 as a potential next-generation treatment for cardiovascular disease. She noted that AZD0708 employs a novel mode of action to inhibit PCSK9, suitable for traditional oral small molecule drug discovery.

Barr also stated that AstraZeneca is advancing the development of AZD0708 as an oral medication for patients who cannot achieve their LDL-C targets with statins alone, aiming to minimize the risk of cardiovascular events.

AstraZeneca acquired AZD0708 from Dogma Therapeutics in 2020 for an undisclosed sum, with the aim of treating dyslipidemia—a condition characterized by elevated levels of fats or lipids in the blood, which increases the risk of clogged arteries, leading to potential heart attacks or strokes. Earlier this year, AZD0708 entered a Phase II clinical trial for patients with dyslipidemia.

The PCSK9 market has garnered interest from numerous major pharmaceutical companies. Novartis’ Leqvio generated $151 million in revenue during the first quarter of 2024, marking a 136% increase from the previous year. Amgen's Repatha also saw significant revenue growth, earning $517 million in Q1 2024, a 33% rise compared to the same period in 2023.

Nonetheless, AstraZeneca may face stiff competition as other PCSK9 inhibitors are showing promising clinical trial outcomes. Merck, for instance, announced last year that its PCSK9 inhibitor MK-0616 had significantly reduced LDL-C levels in hypercholesterolemia patients during a Phase IIb study. The placebo-adjusted reduction from baseline ranged between 41.2% and 60.9%. Merck's candidate is now undergoing a Phase III trial.

These developments indicate a highly competitive landscape in the PCSK9 inhibitor market, with various pharmaceutical giants striving to advance their treatments to address cholesterol-related conditions and reduce cardiovascular risk among patients globally.