AstraZeneca PLC announced its third cardiovascular deal in two weeks April 3, following through on CEO Pascal Soriot’s promise to rebuild the company’s cardiovascular pipeline. The latest deal, in which AstraZeneca’s biologics unit MedImmune LLC acquired private biotech AlphaCore Pharma LLC for an undisclosed sum, is another early-stage play for the big pharma.

With AlphaCore, AstraZeneca gains ACP-501, a recombinant human lecithin-cholesterol acyltransferase (LCAT) enzyme that is believed to play a major role in removing cholesterol from the body and also may increase levels of high-density lipoprotein (HDL) cholesterol, better known as “good cholesterol.”

The product has been studied in a Phase I test for atherosclerosis and also is being developed for a rare hereditary disorder call familial LCAT deficiency in which the LCAT enzyme is absent. The Phase I trial met its primary safety and tolerability endpoint and also showed that ACP-501 raised HDL cholesterol in patients taking it. But the trial enrolled just 16 patients who were followed for 28 days.

LCAT, an enzyme in the bloodstream, is a key component of the reverse cholesterol transport (RCT) system, the process by which cholesterol in the arterial wall is transported to the liver for excretion from the body. In the Phase I trial, the elevation of HDL-C in the study was due entirely to an increased formation of cholesteryl esters, AlphaCore reported.

“This is a totally novel approach, and we know that this enzyme is key in this process of reverse cholesterol transport,” said AstraZeneca’s Cristina Rondinone, head of the Cardiovascular/Metabolic Disease Center (CV/MD) Innovation Medicines Unit (iMED) at MedImmune. “We need to prove it in patients, but we really believe that if it is key, it will have benefit in those patients by removing the cholesterol from the tissues and increasing HDL.”

Ann Arbor, Mich.-based AlphaCore was founded in 2007 by a group of former Parke-Davis (acquired by Pfizer Inc.) researchers who helped discover Lipitor (atorvastatin). President William Brinkeroff said the company, which was funded by angel investors and grants, always had planned on finding a partner for ACP-501 after completing Phase I development.

Benefits And Risks Of Cholesterol Drug Development

If the product’s safety and efficacy hold up in larger trials, the drug could be a potentially lucrative opportunity for AstraZeneca, which needs big money makers to help recover lost sales of blockbusters like Nexium and Crestor, which will face generic competition in the future. But it’s also a risky bet, given the high regulatory bar for new cholesterol drugs and the increasingly competitive commercial field dominated by generic statins.

In addition, the science around the benefits of raising HDL-cholesterol has become muddled after several outcomes trials failed to show that raising HDL-C translates into improved outcomes for patients Also see "HPS2-THRIVE Post-Mortem: Lessons Learned For CV Drug Developers" - Pink Sheet, 18 March, 2013. and Also see "Dalcetrapib Failure Raises Yet More Questions On Value Of Tinkering With HDL Cholesterol" - Pink Sheet, 14 May, 2012.. And, it’s all but a guarantee that a clinical trial program for a product like ACP-501 in atherosclerosis will need to include large outcomes studies to appease FDA.

“We are leaders in this field, and for that, we are used to doing long and extensive clinical trials in this area. Personally, I believe we know how to do it,” said Rondinone.

Plus, Soriot promised investors AstraZeneca would embrace risk as a key to unlocking success in the drug-development process during an overview March 21 in which he unveiled his turnaround plan for the company ([A#00130401001]). He also vowed to rebuild the company’s cardiovascular pipeline, which presently contains little to help the company maintain its leadership position in the field.

AstraZeneca has made cardiovascular disease/metabolism one of its three core therapeutic areas, along with oncology and respiratory/inflammatory disease.

To bolster its cardiovascular research, AstraZeneca announced two deals the same day as the investor overview: an option agreement with messenger RNA developer Moderna Therapeutics LLC for up to 40 programs in exchange for $240 million upfront and a research partnership with Sweden’s Karolinska Institute ([A#14130321004]).

AstraZeneca Makes Good On Vow To Build CV Pipeline With AlphaCore Buy

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