Posts Tagged ‘Lecithin cholesterol acyltransferase deficiency’

Curator: Aviva Lev-Ari, PhD, RN

If Biologics will help increase HDL in wide market penetration, the market share of Statins will be negatively impacted.

The biologics was developed by NIH funding, as reported on 2/14/2012, see last section, below.

NHLBI SMARTT Program Awards AlphaCore Pharma Funding to Manufacture Potential Treatment for Familial Lecithin-Cholesterol Acyltransferase (LCAT) Deficiency


In an Interview I had with the VP of Scientific Affairs at AstraZenaca on 3/18/2013, the Executive Dr. D.S., MD, PhD, told me that the Cardiovascular Therapeutic Area at AstraZeneca is at present and in the future, probably the most important one of all of its businesses to date, thus, the position he is interviewing for, Director of Scientific Affairs Cardiovascular, will be the most powerful one within the Scientific Affairs Office.

Per my discussion of BRILINTA (ticagrelor), referring the VP to my post on this topic on 12/28/2012,

PLATO Trial on ACS: BRILINTA (ticagrelor) better than Plavix® (clopidogrel bisulfate): Lowering chances of having another heart attack

VP said, “the position will be beyond BRILINTA, or Cardiovascular.” A candidate not found yet. AZ keeps on calling, Keeps searching.

AstraZeneca – The Biggest R&D Spenders In Biopharma

Company: AstraZeneca

2011 spending: $5.5 billion
2010 spending: $5.3 billion
Change: +3.6%
Percentage of revenue: 16.3%

Like several other top 10 pharma companies, AstraZeneca ($AZN) saw its R&D expenses climb somewhat in 2011. But this year, as CEO David Brennan unveiled the annual results for 2011, he started with a new restructuring plan. And R&D is intended to bear some of the biggest cuts.

Hit with sliding profits and eviscerated by analysts for one of the weakest late-stage pipelines in the Big Pharma business, Brennan had to do something significant. Of more than 7,000 pink slips being readied, 2,200 were being reserved for R&D as the company moved to shutter R&D facilities in Soedertaelje in Sweden and Montreal. Neuroscience, once a key feature in the pipeline, is being scaled way back, with plans to field a “virtual” team in key hubs.

AstraZeneca became the poster child for the R&D quagmire when Forbes‘ Matthew Herper concluded that AstraZeneca had the worst ratio of R&D costs to approvals in the industry. For a company that went 6 years without a drug approval ahead of the 2009 OK for Onglyza, accumulated setbacks have reached a breaking point.

AstraZeneca, though, can’t cut its way to a turnaround in R&D. That’s going to take new programs and new technologies. It only began to address the issue with a licensing pact for a slate of Amgen antibodies. Research chief Martin Mackay was quick to follow up by telling Reuters‘ Ben Hirschler that more deals were coming. And indeed just weeks later, AstraZeneca acquired a late-stage gout drug with the $1.26 billion buyout of Ardea. The fact that AstraZeneca didn’t bother to stick with its disease strategy, and quickly indicated that it wouldn’t in the future, underscored just how crucial it is to move fast.

Nevertheless, AstraZeneca will find it hard to shake its legacy of failures. Just weeks ago the company was forced to wash its hands of a billion-dollar deal with Targacept ($TRGT) for a prospective depression drug that failed 4 out of 4 late-stage studies. And as criticism mounted, Brennan has been forced to adopt a defensive posture.

“I read and hear and see lots of things, but we’re here trying to change policy, make good decisions and execute our strategy,” the CEO told Bloomberg, vowing to stick to the game plan. “Maybe somebody sees something different, but spending more money does not have a linear increase in the number of returns you get from a research and development perspective.”

AstraZeneca – The Biggest R&D Spenders In Biopharma – FierceBiotech http://www.fiercebiotech.com/special-reports/biggest-rd-spenders-biopharma/astrazeneca-biggest-rd-spenders-biopharma#ixzz2PQN8is2U

On April 3, 2013, FierceBiotech reported that


3 April 2013

AstraZeneca today announced that MedImmune, its global biologics research and development arm, has acquired AlphaCore Pharma, an Ann Arbor, Michigan-based biotechnology company focused on the development of ACP-501, a recombinant human lecithin-cholesterol acyltransferase (LCAT) enzyme.

LCAT, an enzyme in the bloodstream, is a key component in the reverse cholesterol transport (RCT) system, which is thought to play a major role in driving the removal of cholesterol from the body and may be critical in the management of high-density lipoprotein (HDL) cholesterol levels.  The LCAT enzyme could also play a role in a rare, hereditary disorder called familial LCAT deficiency (FLD) in which the LCAT enzyme is absent.

Cardiovascular and metabolic disease is a core therapy area for AstraZeneca’s small and large molecule research.

“As the science in this area continues to evolve, we are committed to exploring unique pathways that could lead to new combination or standalone therapies for patients living with chronic and acute cardiovascular diseases,” said Dr. Bahija Jallal, Executive Vice President, MedImmune. “Cardiovascular disease is projected to remain the single leading cause of death worldwide over the next decade and beyond. Through novel approaches like LCAT, we hope to shift the treatment paradigms in this area to help prevent and treat these conditions.”

In 2012, results from a Phase I clinical trial of ACP-501 met the primary safety and tolerability endpoints.  No serious adverse events were reported.  ACP-501 also met the study’s secondary endpoints by rapidly and substantially elevating HDL cholesterol.  The data from this study support ongoing clinical development of ACP-501.

MEDIMMUNE, ASTRAZENECA’S BIOLOGICS ARM, ACQUIRES ALPHACORE PHARMA – FierceBiotech http://www.fiercebiotech.com/press-releases/medimmune-astrazenecas-biologics-arm-acquires-alphacore-pharma#ixzz2PQL73X3f

 AstraZeneca gambles on cardio therapy in AlphaCore buyout

By Ryan McBride

In another early-stage bet, AstraZeneca’s MedImmune unit acquired the biotech AlphaCore Pharma. The deal comes as AstraZeneca ($AZN) reboots a floundering R&D effort and adds a recombinant LCAT enzyme therapy from AlphaCore that could combat cardiovascular disease.

MedImmune, the biologics division of Astra, faces years of additional development before AlphaCore’s ACP-501 becomes part of the London-based pharma group’s late-stage pipeline, which has many holes yet to be filled. Last year, Ann Arbor, MI-based AlphaCore touted Phase I work on ACP-501, reporting that the enzyme therapy was well-tolerated and quickly boosted levels of HDL or “good” cholesterol in patients.

AZ CEO Pascal Soriot

New AstraZeneca CEO Pascal Soriot has signaled his desire to wager on new science amid an overhaul of R&D announced last month that will cost 1,600 research jobs across the company and after the ouster of former R&D chief Martin Mackay in January. Bahija Jallal, executive vice president of MedImmune, survived the round of cutbacks and plans to pursue new biologics such as ACP-501, which she stated could treat both acute and chronic cardiovascular disease.

“Cardiovascular disease is projected to remain the single leading cause of death worldwide over the next decade and beyond,” Jallal said. “Through novel approaches like LCAT, we hope to shift the treatment paradigms in this area to help prevent and treat these conditions.”

The ACP-501 is an engineered version of the natural LCAT enzyme from the liver that plays a role in ridding the body of cholesterol and keeping up levels of beneficial HDL cholesterol. The candidate could aid millions of patients with cholesterol problems as well as those with a rare inherited disease called familial LCAT deficiency that robs the body of the enzyme.

Bahija Jallal, EVP of MedImmune

The AlphaCore buyout comes on the heels of AstraZeneca’s sizable $240 million upfront payment to Moderna Therapeutics to get in early on the startup’s preclinical programs that use messenger RNA to turn cells in the body into makers of healing proteins. The financial details of the AlphaCore buyout weren’t disclosed.

Still, analysts expect Soriot to pull the trigger on larger deals to bolster the late-stage pipeline or even provide marketed products as AstraZeneca faces the impact of patent expirations on blockbuster cholesterol pill Crestor and the heartburn med Nexium. As Reuters noted, the company has only 6 drugs in late-stage development and aims to double that number by 2016.

February 14, 2012 09:17 AM Eastern Daylight Time

NHLBI SMARTT Program Awards AlphaCore Pharma Funding to Manufacture Potential Treatment for Familial Lecithin-Cholesterol Acyltransferase (LCAT) Deficiency

ANN ARBOR, Mich. & ROCKVILLE, Md.–(BUSINESS WIRE)–AlphaCore Pharma, a biopharmaceutical company, and Advanced Bioscience Laboratories (ABL), a biomedical contract research and manufacturing company, today announce funding from the National Institutes of Health, National Heart, Lung and Blood Institute (NHLBI) “Science Moving towards Research Translation and Therapy” (SMARTT) program, to manufacture recombinant human lecithin-cholesterol acyltransferase (rhLCAT) for the treatment of familial LCAT deficiency.

“This is a significant step towards developing a treatment for familial LCAT deficiency. We are pleased by the strong support from the NHLBI and ABL and look forward to advancing this program.”

Also known as ACP-501, rhLCAT represents a promising new approach in the fight against atherosclerotic cardiovascular disease, and has demonstrated preclinical efficacy in promoting HDL maturation and cholesterol flux, a natural process by which cholesterol is removed from the body. Currently, ACP-501 is in Phase 1 clinical development with the eventual goal of reducing the risk of cardiovascular events in patients presenting with acute coronary syndrome. Manufacturing support from the NHLBI SMARTT program will enable production of additional material that will be used to determine the safety and efficacy of rhLCAT enzyme replacement therapy for patients with familial LCAT deficiency – a potentially life-threatening illness for which there is no FDA-approved treatment.

“This is a significant step towards developing a treatment for familial LCAT deficiency. We are pleased by the strong support from the NHLBI and ABL and look forward to advancing this program.” said AlphaCore President, Bruce Auerbach.

The enzyme, rhLCAT, will be produced by ABL in its Rockville, MD biologics production facility under a contract from the NHLBI SMARTT program. Dr. Thomas VanCott, ABL’s President and Chief Executive Officer stated, “ABL is privileged to be working with AlphaCore Pharma in support of their ACP-501 (rhLCAT) program. Research in rare genetic diseases can encounter funding hurdles, yet through this NHLBI-sponsored manufacturing project we have the potential to advance an urgently needed enzyme replacement therapy. This effort further demonstrates ABL’s expertise of partnering with the NIH to support major development programs and our commitment to deliver the highest quality cGMP biologics to our clients in a cost-effective manner.”

Peter Greenleaf, chief executive of MedImmune. (Jeffrey MacMillan – JEFFREY MACMILLAN)Peter Greenleaf is stepping down down as president of Gaithersburg-based biotechnology giant MedImmune, according to a company spokesman, to take the helm of parent company AstraZeneca’s Latin America business.

He will be replaced by Bahija Jallal, who currently serves as MedImmune’s executive vice president of research and development. Jallal joined the company in 2006 as vice president of translational sciences.

The leadership change comes as MedImmune was formally designated a biologics research and development site for AstraZeneca, meaning Jallal will report directly to AstraZeneca chief executive Pascal Soriot, said company spokesman Mike O’Brien.

He added that MedImmune’s commercial organization will now report into AstraZeneca’s North American business and its manufacturing group will be folded into AstraZeneca’s global operations group.

“There’s no new news on jobs today,” O’Brien said. “The driver for these changes is not cost but even faster decision-making in key areas of the business and a need to reduce complexity.”

O’Brien said Greenleaf will continue to be based in Maryland, where he has become a figure­head of sorts for the life sciences industry.

Greenleaf was an advocate for Democratic Gov. Martin O’Malley’s InvestMaryland initiative, which allocates state money for investment in local upstarts. He serves as chairman of the Maryland Venture Fund Authority, a nine-member board assigned to oversee its implementation.

MedImmune has long been an anchor of Maryland’s biotechnology hub along the Interstate 270 corridor. The company was purchased by AstraZeneca in 2007 for $15.6 billion, a sales price that some industry observers still question.

The Washington Business Journal reported the personnel changes earlier.



Mineo C, Yuhanna IS, Quon MJ, Shaul PW., (2003). HDL-induced eNOS activation is mediated by Akt and MAP kinases. J. Biol. Chem., 278:9142–9149.

Shaul, PW and Mineo, C, (2004). HDL action on the vascular wall: is the answer NO? J Clin Invest., 15; 113(4): 509–513.

Other related articles to this topic on the Open Access Online Scientific Journal include the following:

Aviva Lev-Ari, PhD, RN, 4/7/2013


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