AstraZeneca nabs next-gen oral PCSK9 inhibitor asset from Dogma Therapeutics


The PCSK9 inhibitor market has to date not made good on its major sales promise, with the likes of Amgen and Sanofi in a price-cutting war for the heart drugs.

Despite large outcome trials showing a 15% to 20% reduction in cardiac events using these drugs, the cost-effectiveness and wide use of antibody-based PCSK9 injectables has been questioned.

Alternate approaches to PCSK9 inhibition have also been stymied by the expansive binding surface targeted by the antibodies, and, to date, only indirect approaches to PCSK9 inhibition by small molecules have been reported.


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Last year, a new startup emerged from stealth, with a helping hand from CRO Charles River Laboratories, to help solve this problem. Dogma Therapeutics tapped its platform and discovered small-molecule inhibitors that directly bind to a novel, cryptic binding pocket in PCSK9.

When given by mouth to dyslipidemic nonhuman primates in preclinical tests, the biotech said it found its oral version saw “significant and robust lowering of LDL-C following multiple weeks of administration.”

Now, AstraZeneca wants in at the front door of this next-gen approach, penning a deal to snap up its PCSK9 inhibitor program and take it into the clinic next year to see how well it can work in humans.

The licensing deal, financials of which were not made public, will see AZ  take the program forward into clinical development for dyslipidemia, or abnormal amount of lipids in the blood, and familial hypercholesterolemia, a common genetic condition that causes high cholesterol.

RELATED: Amgen escalates PCSK9 pricing war with permanent 60% price cut on Repatha

“Raised LDL cholesterol is a key risk factor for cardiovascular disease and is estimated to cause 2.6 million deaths worldwide every year,” said Mene Pangalos, executive vice president of biopharmaceuticals R&D at AstraZeneca.

“Whilst PCSK9 is a well validated target for lowering LDL cholesterol it has been a hugely challenging target to inhibit with small molecules. This agreement with Dogma Therapeutics offers us the opportunity to develop the first small molecule, orally bioavailable PCSK9 inhibitor, for patients at risk of cardiovascular disease,” Pangalos said.

“We have built a robust data package that highlights the cholesterol-lowering and safety potential of our oral PCSK9 programme,” added Brian Hubbard, chief of Dogma Therapeutics. “This agreement with AstraZeneca meets our strategic goal to accelerate access to patients unable to meet target LDL cholesterol.”

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