AstraZeneca said Monday its experimental pill lowered "bad" LDL cholesterol by 51%. The results showed promise against rival drugs from Merck and NewAmsterdam Pharma, but AstraZeneca stock fell.
The study added AstraZeneca's AZD0780 to standard statin therapy. After 12 weeks, patients had a 50.7% reduction in LDL cholesterol.
In comparison, patients given Merck's MK-0616 for eight weeks experienced a 41.2% to 60.9% reduction in LDL cholesterol, depending on the dosage. After 12 weeks, recipients of NewAmsterdam's obicetrapib had a 36.3% cut in LDL. That continued onto a 41.5% drop over the course of a year.
High LDL cholesterol is tied to poor cardiovascular outcomes, including heart attacks and strokes. Still, more than 70% of patients taking statins aren't reaching their LDL cholesterol goal. The unmet need is "massive," says Mina Makar. Makar heads up AstraZeneca's global cardiovascular, renal and metabolism biopharmaceuticals business unit.
"Dyslipidemia still is the No. 1 driver of (cardiovascular) events and death," he told Investor's Business Daily. "It's still 2 billion people worldwide who are suffering from it."
AstraZeneca stock slumped 0.4% to 73.50 after unveiling its study results. Meanwhile, IBD's Medical-Diversified industry group ended the regular session roughly flat, clawing back after diving earlier following the resignation of the Food and Drug Administration's Peter Marks. Marks directs the FDA's Center for Biologics Evaluation and Research.
AstraZeneca Stock: Why Pills Could Rule Shots
The experimental pills from AstraZeneca and Merck work by lowering PCSK9 protein. This protein plays a role in regulating LDL cholesterol levels. NewAmsterdam's drug uses a different mechanism, blocking a plasma protein called CETP to increase "good" HDL cholesterol and lower LDL levels.
Merck's drug is a macrocyclic peptide, while AstraZeneca's is a small molecule. Peptide-based drugs must be taken in a fasted state, however, to allow for proper absorption. That won't be the case for a small molecule like AZD0780, Makar said.
This isn't the first time PCSK9 blockers have been in the limelight.
Regeneron Pharmaceuticals and Sanofi sell an injectable drug called Praluent, while Amgen makes Repatha. But the shots have faced a tough commercial environment. Insurers were slow to cover them. And injections must be stored at specific temperatures, making their uptake difficult in some countries abroad.
Makar expects the daily pills to have an easier commercial time. "It would be a mistake for anybody to think of our oral small molecule through the lens of the current injectable PCSK9 market," he said. "It needs to be looked at through the lens of the broader lipid population, the statin population and where is the unmet need."
$5 billion Projected Sales Peak
Handelsbanken analyst Mattias Haggblom is bullish on the outlook for oral PCSK9s.
He says AstraZeneca has "one pill to rule them all" and projects $5 billion in peak sales for AZD0780. But he doesn't think investors in AstraZeneca stock are playing close attention to it. The results Monday could change their tune.
"We note AstraZeneca in December initiated additional trials to test combinations with already approved agents suggesting confidence in the program," he said. "Phase II data due later this year and positive phase III data from Merck are the next building blocks to start generating interest for this vastly neglected asset."
AstraZeneca is closely looking at the combination approach, says Makar. In some parts of the world, it would be easier to combine a statin and the PCSK9 blocker into one pill. The company could also consider testing a combination of AZN0780 with its GLP-1 for weight loss.
"The beauty of AstraZeneca's (cardiovascular, renal and metabolism) strategy and pipeline is we have molecules across the heart, the kidneys, hypertension, dyslipidemia, weight and diabetes," he said. "We really have what I believe is probably the most robust pipeline. So, it gives us a lot of flexibility as to the populations we think we can help."
But, for now, the company is moving with "all speed" to push AZD0780 into Phase 3 testing. Haggblom, the Handelsbanken analyst, expects AstraZeneca to launch its cholesterol pill in 2028.
AstraZeneca stock has a promising IBD Digital Composite Rating of 96, which puts it in the top 4% of all stocks when it comes to fundamental and technical measures.
Follow Allison Gatlin on X/Twitter at @AGatlin_IBD.
