Replies to post #120692 on Biotech Values

[poorgradstudent]

Somewhat OT:

In a way I feel for the NIH. This was a well run trial that has important consequences for both treatment and treatment cost. But it seems like human nature may actually foil their achievement. You can see some of that resistance just in the discussion on this board in the last ~24 hours.

[gdollasign]

Complete common sense speaking but wouldnt that lend to plain old bad planning in trial design?...3 times?? The only true marker that gets a drug of this type approved i.e. AMRN is to show an actual CV benefit (read fewer incidence). If AMRN cant show it then it will end up the same way as the others mentioned. If it can then we are a mere percentage of future market cap. I dont know if either the ANCHOR or MARINE results highlighted such a benefit. Guess I will have to look.

[Regulardoc]

Dew,


The main action of Zetia is to lower LDL.

I believe you meant to state that Zetia lowers LDL, rather than raises HDL. Zetia is very effective in lowering LDL, yet the study (if I recall correctly) showed increased, rather than decreased intimal thickness.

[biomaven0]

>Enemy action

But there is the confounding Arbiter 6-HALTS trial where Niaspan plus statin was shown to be superior (based on CIMT) to Zetia plus statin.

http://content.onlinejacc.org/cgi/content/full/j.jacc.2010.03.017v1

Maybe carotid intima-media thickness isn't in fact a good endpoint or maybe Zetia actually did harm.

Peter

[DewDiligence]

Teva, MRK settle Vytorin/Zetia US patent case:

http://www.bloomberg.com/news/2011-07-08/teva-won-t-sell-generic-vytorin-until-2017-settling-merck-patent-lawsuit.html

The settlement terms have not been disclosed.

Unless MYL prevails against MRK in a separate lawsuit, Vytorin/Zetia will not go generic in the US until 2017.

[DewDiligence]

New study shows lipid benefits of soy protein:

http://www.nature.com/ejcn/journal/vaop/ncurrent/full/ejcn2011168a.html

I’m not sure what affiliation, if any, the study authors have to any company that stands to benefit from these findings.

[DewDiligence]

NIH recommends routine cholesterol screening for children:

http://www.reuters.com/article/2011/11/11/usa-cholesterol-children-idUSN1E7AA1U020111111

[DewDiligence]

LLY’s Evacetrapib Boosts Good Cholesterol

[Evacetrapib is a CETP inhibitor, i.e. it’s from the same drug class as Roche’s Dalcetrapib, MRK’s Anacetrapib, and PFE’s infamous Torcetrapib.]

http://online.wsj.com/article/SB10001424052970204190504577040163501008348.html

›NOVEMBER 16, 2011
By JENNIFER CORBETT DOOREN

A study involving Eli Lilly & Co.'s experimental drug evacetrapib showed it was able to boost good cholesterol levels while lowering the bad kind.

The study was presented Tuesday at the American Heart Association's annual meeting in Orlando, Fla., and published in the Journal of the American Medical Association. It was funded by Eli Lilly and led by doctors at the Cleveland Clinic.

Evacetrapib is designed to inhibit cholesteryl ester transfer protein, or CETP, which is involved in transferring cholesterol particles from HDL—considered the "good" cholesterol—to LDL, referred to as "bad" cholesterol.

CETP inhibitors are primarily designed to raise good cholesterol levels and could be a new way to prevent cardiovascular problems like heart attacks and strokes. The widely used cholesterol-lowering drugs known as statins target LDL or bad cholesterol.

Merck & Co. and Roche also have CETP drugs in development. Daniel Rader, scientific director of clinical research at the cardiovascular institute of the University of Pennsylvania, said the three CETP inhibitors target the same mechanism but work in different ways.

"This is a very exciting new drug that appears to be safe," he said, referring to the new Lilly drug. Dr. Rader, whose research focuses on HDL cholesterol, was asked to discuss the evacetrapib study on behalf of the American Heart Association.

Having naturally high levels of HDL is associated with lower cardiovascular risks, making HDL another target for drug therapy, doctors said. Still, it isn't clear if raising HDL translates into a reduction of cardiovascular events like heart attacks and strokes [see #msg-63656000]. Other drugs like niacin are used to raise HDL but can be difficult drugs to tolerate for many patients, so researchers are looking for new ways to raise HDL.

Steve Nissen, one of the Cleveland Clinic doctors involved in the evacetrapib study, said larger studies will be needed to show if CETP inhibitors are able to reduce cardiovascular events such as heart attacks and strokes.

David Moller, Eli Lilly vice president of endocrine and cardiovascular research and clinical investigation, said the company is planning larger studies of evacetrapib.

In 2006, Pfizer Inc. ended development of its CETP inhibitor, torcetrapib, after a study showed an increase in deaths and cardiovascular events among patients receiving the drug. The move, in turn, slowed development of the drug class. So far, mid-stage data involving CETP drugs from the other companies haven't shown the same risk.

If the drug class does prove successful, Dr. Nissen and other doctors say it could be as big as statins. Despite the success of statins like Lipitor, Crestor and Zocor, cardiovascular disease is still the leading cause of death among Americans. Doctors and pharmaceutical companies are looking for new kinds of treatments.

The study of evacetrapib involved about 400 patients with elevated LDL levels or low HDL levels. There were 10 groups in the study looking at three doses of evacetrapib alone and in combination with the three most-prescribed statins: Crestor, Lipitor and Zocor. Patients had cholesterol levels measured at the study's start and after 12 weeks.

When given with statins, a 100-milligram dose of evacetrapib was able to increase HDL levels by 78.5% to 88.5%. It also lowered LDL cholesterol by 11.2% to 13.9%.

There was no increase in blood pressure and no increase in levels of aldosterone or cortisol, two hormones that were elevated in the earlier Pfizer torcetrapib trial.

Roche is currently the furthest along in development with larger studies of its CETP inhibitor dalcetrapib well under way. Terence Hurley, a Roche spokesman, said the company hopes to file for regulatory approval in the U.S. in 2013.

Merck started a 30,000-patient study of its drug anaceptrapib last year. The research is expected to be completed in 2017, according to information listed about the study on clinicaltrials.gov.‹

[DewDiligence]

This blurb from the AHA is not exactly a shocker:

http://finance.yahoo.com/news/Middle-Age-Blood-Pressure-pz-4012538761.html?x=0

People who maintain or reduce their blood pressure to normal levels during middle age have the lowest lifetime risk of cardiovascular disease, while those with an increase in blood pressure have the highest risk.

[DewDiligence]

Heart disease linked to variant of Y chromosome:

http://www.nytimes.com/2012/02/09/health/research/heart-disease-risk-may-be-tied-to-y-chromosome.html

[DewDiligence]

Grifols touts plasmapheresis for improved lipid profile:

http://finance.yahoo.com/news/grifols-study-suggests-repeated-plasmapheresis-152700946.html

Grifols, a global healthcare company that specializes in the production of biological medicines derived from human plasma, presented study results today suggesting that the plasmapheresis process may reduce levels of low-density lipoprotein (LDL) or "bad" cholesterol as well as total cholesterol in individuals who have high baseline levels. The study also suggests that plasmapheresis could increase levels of "good" (HDL) cholesterol among individuals with low baseline levels.

…Using a statistical model known as multi-variable regression to analyze the study data, the researchers estimated that plasmapheresis could reduce the levels of low density lipoproteins (LDL) or "bad" cholesterol by more than 30 mg/dL among individuals with high levels (> 160 mg/dL) or higher than desirable levels (>130 mg/dL), when plasmapheresis procedures are performed two to four days apart.

…The cholesterol-lowering effects of plasmapheresis appeared to last only as long as the procedure continued at regular intervals, with cholesterol levels gradually returning to baseline following long periods without plasmapheresis.

Comments?

[DewDiligence]

An intuitive finding from ACC:

http://www.reuters.com/article/2012/03/24/us-heart-pictures-idUSBRE82N0DB20120324

Patients who view images of their hearts and see for themselves the buildup of calcium within their artery walls become more compliant about taking their cholesterol-fighting drugs and are more likely to lose weight, researchers said on Saturday.

[DewDiligence]

The evidence against raising HDL as a means of lowering cardiovascular risk
just took another hit. (Using the Ian Fleming terminology in #msg-63656000,
we are now well beyond the point of declaring enemy action!)

http://www.bostonglobe.com/lifestyle/health-wellness/2012/05/16/study-questions-whether-raising-good-cholesterol-reduces-heart-attack-risk/yyCUuBXGTXDTxdq8EYpJwJ/story.html

Raising levels of “good’’ cholesterol may not be so good for you after all… In the study in the medical journal The Lancet, a team led by researchers from Massachusetts General Hospital and the Broad Institute examined the health of more than 100,000 people, some of them with genetic variations that elevated their levels of HDL, and found that those variations did not protect against heart attacks.

…To test whether raising HDL is protective, the scientists in the new study looked at a gene variation that is present in about 2.6 percent of the population and raises HDL levels, with no effect on other cardiovascular risk factors. People with that gene should have a 13 percent decreased risk of heart attack, the researchers calculated. But when they compared them with people who did not have the gene, there was no difference in heart attack risk.

In a second study, researchers examined a panel of 14 genetic variations that raised HDL levels and found that inheriting those variations did not confer protection against heart attacks, either.

… Outside scientists said the new study does not definitely show that raising HDL always fails to protect against heart attacks. For example, there may be subtypes of HDL, some of which reduce and some of which promote cardiovascular risk.

[DewDiligence]

MRK’s Tredaptive fails phase-3 outcomes study in cardiovascular disease; this is a continuation of negative outcomes for niacin therapy dating back to the AIM-HIGH study of ABT’s Niaspan (#msg-63617748):

http://finance.yahoo.com/news/merck-announces-hps2-thrive-study-133000558.html

…adding the combination of extended-release niacin and laropiprant to statin therapy did not significantly further reduce the risk of the combination of coronary deaths, non-fatal heart attacks, strokes or revascularizations compared to statin therapy. In addition, there was a statistically significant increase in the incidence of some types of non-fatal serious adverse events in the group that received extended-release niacin/laropiprant.

Ouch. MRK has dropped plans to seek approval for Tredaptive in the US; in countries where the drug is already approved, sales will presumably plummet.

[BioChica]

My view is: If the medical community where treating CVD properly it would not be the number one killer! What are they doing wrong??

So will EPA be part of the solution? Maybe, we hope this is the case!

[jessellivermore]

Hi Dew...

You quote Auric Goldfinger, and then give us Odd Job..

For the life of me I can not figure out how fibrates and niacin's failure to improve CVD outcomes is bad news for Vascepa, and am confused about exactly how these two relate to EPA...Regardless of your take on the outcomes studies on these two separate and different acting drugs; regardless of your take on JELIS..There was no evidence even in subsets that the drug (EPA) made things worse..

In the meantime there is a ton of scientific evidence on why EPA will improve not only CVD outcomes, but the outcomes of most of the rest of the "degenerative diseases"..Yes I understand clinicians do not read the scientific evidence. Be assured there are a lot of educated people out there who can and will read the literature because they have one or more conditions, because they have a stake in it..their lives..One of the effects of the lack of respect for doctors, and the collective intelligence of the internet is now that patients can educate their busy doctors, and the busy doctors will listen and get educated if they want patients and not law suits..

I can not predict the outcome of the AdComm, and would be surprised if there was not some dissenting notes, but be clear V had no role in the studies you mention..I would highly recommend you doing some serious study on how EPA works..and if you can find major flaws, then I am all ears...In the meantime I humbly suggest you may be passing on a great opportunity.

":>) JL