Another Oops for Another Big Pharma Drug
Another day, another story about Big Pharma fraud mistakes. Evolocumab, marketed as Repatha, has made scientific news recently and not for the right reasons. Repatha was licensed in 2015 by government regulators based on it’s ability to lower LDL cholesterol levels, but not for its effect on cardiovascular disease or mortality.
Repatha is actually a monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9) from binding to receptors on the liver so there are more receptors available to remove LDL from the blood. This is a different mechanism of action compared to statins such as Lipitor. In previous blog posts, I’ve highlighted meta-analysis of statins that show virtually no mortality reduction benefit from statins.
The results of the FOURIER trial for evolocumab were published in 2017 in the New England Journal of Medicine (NEJM). The trial was supposed to last for 56 months, but was terminated early supposedly for apparent benefit after median follow up of only 2.2 years.
In the NEJM article, the study authors reported that total and cardiovascular mortality was higher in the evolocumab group than the placebo group, but that non-fatal myocardial infarction and strokes were reduced. Translation, this doesn’t stop people from dying, they just die of something else which somehow qualifies as a win in the bizarro world of Big Pharma.
However, in Restoring mortality data in the FOURIER cardiovascular outcomes trial of evolocumab in patients with cardiovascular disease: a reanalysis based on regulatory data published in the British Medical Journal, a group that is reviewing drug trials published in medical journals noticed inconsistencies in the published data versus information contained in the Clinical Study Report (CSR). The CSR is a technical document prepared by the manufacturer and submitted to regulators as part of the approval package for drug evaluation. It contains information about the trial’s protocol, amendments, inclusion and exclusion criteria, outcome definitions and measurement, efficacy and safety results and statistical analysis plan. The main FOURIER CSR is over 25,000 pages.
Effectively, they discovered that a FOURIER clinical-events committee reassigned deaths to causes other than what was reported by the local physician responsible for reporting the death. An independent committee blindly re-adjudicated and restored mortality according to information in the CSR. After re-adjudication, deaths of cardiac origin were even higher in the treatment group and lower in the placebo group than what was published in the NEJM study.
That this drug was even approved in the first place based on the fact that the original published study showed greater total and cardiovascular mortality among the treatment group vs the placebo group is more evidence that whether or not a treatment actually improves health outcomes is irrelevant. This is also further indication (to me anyway) that LDL is not the underlying cause of cardiovascular disease, and artificially manipulating LDL lower provides no real absolute benefit. Stopping a trial early is also a great sign in general that something is very wrong with the treatment, and they don’t want to discover more issues.
Cholesterol drugs are easy to pick on, but the reality is that the vast majority of medications do not address the underlying cause of disease nor do they do much to improve health outcomes. The bar to get a drug or vaccine approved is actually quite low. As long as a drug manufacturer can show that some arbitrary numbers such as LDL levels or blood pressure are impacted by treatment slightly more than a placebo, that’s good enough for the regulators.
As noted in previous posts, anti-depressants may increase or decrease levels of neurotransmitters, but meta-analysis show little to no benefit for most of these medications. Biogen’s new Alzheimer’s drug, Aduhelm, does indeed reduce the buildup of amyloid plaque in the brain, but does not improve the outcome of patients and in fact has serious safety issues. Even though the safety panel voted nearly unanimously against approving this drug the FDA went ahead and approved it anyway. Vaccines really only need to show that they raise antibody levels. Whether or not they actually prevent infection, transmission, or sickness is at best a secondary consideration if it even factors into the equation at all.
Why do these treatments gain approval? Quite simply, a helluva lot of money is at stake, and the FDA receives a huge chunk of its funding from pharmaceutical companies. They are not going to bite the hand that pays their salaries. And, if they do right by pharmaceutical companies in their roles at the FDA, they are often rewarded with job offers at pharmaceutical companies making even more money.
Doctors are unfortunately trained to identify symptoms and prescribe drugs, not to identify underlying cause of disease which often does not require medical intervention to treat or reverse. The entire system is rotten from top to bottom putting unsuspecting patients in harm’s way while picking their pockets.