• Will Big Pharma Ever Give Up On This Experimental Cholesterol Drug?

    Posted March 20, 2015: by Bill Sardi

    How many more negative studies before Big Pharma abandons research on a class of cholesterol altering drugs that has been nothing but problematic?

    Over 8 years ago a major pharmaceutical company’s foray into a new class of cholesterol drugs that raise HDL (high-density lipoprotein), the so-called good cholesterol that shuttles cholesterol from the arteries back to the liver, was terminated because raised the risk of heart problems and death. Over $800 million had been spent to research and develop this drug at that time. [Nature Reviews Drug Discovery March 2011]

    Big Pharma never gave up on this new class of cholesterol medicines which are now being hailed by a major investment research group as a “novel” class of drugs “that will stimulate significant growth … over the latter half of the 2013-2023 forecast period.” The future investment profile for this class of drugs is predicted to “generate high sales” with a number of these drugs being called “emerging blockbusters.” [Decision Resources Dec 3, 2014]

    And this class of LDL-bad cholesterol/HDL-good cholesterol balancers are being touted for another reason. They mimic a gene mutation in the CETP (cholesterol ester transfer protein) gene which is found among American Ashkenazi Jewish women who live long healthy lives. The idea is that this class of drugs could “someday protect humans from the undesirable effects of aging.” [The Algemeiner.com March 15, 2015]

    While there are published report linking mutations in the CETP gene with longevity, other reports indicate that mutations in the CETP gene do NOT result in longevity in human populations. [Age April 2013; Molecular Biology Reports Jan 2014; Angiology March 2014; Mechanisms Ageing Development 2005; Journal Molecular Medicine 2003] The CETP gene mutation may actually increase the risk for death. [PLoS One Aug 15, 2013] CETP inhibitors have been crossed off the list of potential anti-aging agents. [Biogerontology April 2008]

    Surprisingly, one study shows a CETP gene mutation even accelerates the onset of Alzheimer’s disease. [Aging Cell April 2012]

    But it appears Big Pharma and Wall Street have so much to lose on their bets on this drug class that they won’t let go of it and it continued research studies may be costing thousands of people who have enrolled in clinical studies to lose their lives.

    Five years ago researchers said the rationale behind these HDL-raising drugs “appears to be extremely weak” and that “CETP inhibition should not be pursued” in particular because of a “dramatic rise in infections” reported in human clinical studies. [Cardiovascular Therapy 2008] Yet the drum still beats for CETP inhibitors.

    As of February 2015 a major drug company notes that it is extending its massive Phase III human trial of its CETP inhibitor because the company wants to “give the data more time to mature.” In other words, maybe there is some long-term benefit that can justify approval of their drug since it isn’t working in the short term. [FierceBioTech.com]

    A recent analysis of various drugs, including niacin and CETP inhibitors revealed that even though these medicines increased HDL-good cholesterol that “neither niacin, fibrate cholesterol lowering drug nor CETP inhibitors reduced all-cause mortality, coronary heart disease mortality, heart attacks or stroke in patients treated with statin drugs.” [British Medical Journal July 18, 2014]   When will public health authorities have the gumption to halt these studies?

    There are two major human trials of CETP inhibitors underway that won’t be completed till 2015 and 2017. The evidence involving CETP inhibitors is mounting up and it isn’t positive. A trial of a highly touted CETP inhibitor had to be prematurely terminated due to increased mortality. [Journal Lipid Research May 2010]   Two other studies have found that lower secretion of CETP actually increases the risk for heart attacks.   Here is how researchers rang the alarm on CETP inhibiting drugs:

    Given that the tide of evidence has turned so strongly against CETP inhibition in recent years, the question must be asked of whether it is now ethical to continue with the two Phase 3 trials in progress. A clinical trial is considered to be ethical only if it has a sound scientific basis and a favorable risk-benefit balance. The two trials in question no longer satisfy either requirement, as there is clearly a strong possibility that the drugs will have exactly the opposite effect on cardiovascular disease to that intended. Some might argue that there is no cause for concern, as morbidity and mortality are being regularly reviewed by data monitoring committees. However, such committees can intervene only when pre-specified statistical criteria have been met, by which time many participants may have suffered harm.

    Carrying on and hoping for the best is not an acceptable option. An independent review is urgently needed to determine if the trials should be discontinued. [F100Research June 10, 2014] Do the subjects who have enrolled in these studies know their lives are at undue risk?

    ©2015 Bill Sardi, Knowledge of Health, Inc.

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