AstraZeneca Touts Early-Stage Results for Oral PCSK9 Inhibitor

AstraZeneca plant_iStock, Roland Magnusson

Pictured: AstraZeneca's production plant in Sweden/iStock, Roland Magnusson

AstraZeneca announced Wednesday Phase I trial data for its PCSK9 inhibitor, AZD0708, which showed a statistically significant reduction of low-density lipoprotein cholesterol in patients with high “bad” cholesterol or hypercholesterolemia.

The trial investigated the safety, tolerability and pharmacodynamics of AZD0780 in lowering low-density lipoprotein cholesterol (LDL-C) levels. The results demonstrated that the candidate reduced LDL-C levels by 52% for patients also taking rosuvastatin, a statin that helps reduce bad cholesterol and raise good cholesterol. AZD0780 also showed a 78% total reduction from the baseline in treatment-naïve patients with hypercholesterolemia.

AstraZeneca said preliminary data comparing dosing with food versus fasting shows more “dosing flexibility” with food. No serious adverse events were recorded and AZD0708 was well tolerated, according to the company.  

“The role of PCSK9 in cholesterol management is well established, and the compelling data generated with AZD0780 demonstrate the potential of this molecule for effective inhibition of this target and a possible next generation treatment for people with cardiovascular disease,” Sharon Barr, executive vice president of biopharmaceuticals R&D at AstraZeneca, said in a statement. “AZD0780 inhibits PCSK9 via a novel, previously unexplored, mode of action that is compatible with traditional oral small molecule drug discovery.”

Barr added that AstraZeneca is “progressing development” of AZD0780 as an oral medicine for patients who cannot meet LDL-C targets with statins alone to reduce the risk of cardiovascular events.

The pharma picked up the candidate in 2020 from Dogma Therapeutics for an undisclosed amount, intending to treat dyslipidemia. AZD0780 moved into a Phase II clinical trial in patients with dyslipidemia earlier this year. Dyslipidemia elevates the level of fats or lipids and can increase the risk of clogged arteries, leading to further health issues such as heart attack or stroke.

The PCSK9 market has attracted several big drugmakers. Novartis’ Leqvio generated $151 million in revenue in the first quarter of 2024, a 136% jump from last year, while Amgen’s Repatha raked in $517 million in Q1 2024, a 33% increase compared to the same period in 2023.

However, AstraZeneca potentially faces other competition as other PCSK9 inhibitors have shown encouraging clinical trial results. Merck announced last year that a Phase IIb study evaluating its PCSK9 inhibitor MK-0616 in hypercholesterolemia patients had “significantly” reduced LDL-C levels from the placebo, with the placebo-adjusted reduction from the baseline ranging from 41.2% to 60.9%. Merck’s candidate is currently in a Phase III trial.

Tyler Patchen is a staff writer at BioSpace. You can reach him at Follow him on LinkedIn.

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