Published on July 19, 2021
Over the past couple weeks, Americans have heard a great deal about FDA’s recent approval of aducanumab (aka Aduhelm) as a treatment for Alzheimer’s Disease (AD). These negative reports surely came as no surprise to its developer, which had already scrapped aducanumab after concluding that it had failed in two prospective studies.
Although FDA approval was crucial for Biogen, which is struggling financially, Biogen announced to shareholders that it was ready to move on and cut its losses. But after they did, FDA and Biogen had some sort of secret communiqué in May 2019, potentially in violation of FDA protocols, where the FDA and top Biogen executives discussed the matter and promoted a scientifically unjustified re-analysis of aducanumab.
It is highly inappropriate and even unethical for FDA to meet in secret with entities it regulates. But given the Biden administration’s pledge to defeat Alzheimer’s with a “Manhattan Project”-style effort, FDA’s sudden courtship of Biogen and abandonment of governing scientific standards appears to be the result of White House pressure placed on key members of FDA’s career senior executive leadership team.
The FDA has strict requirements for drug approval. Among other requirements for FDA to even consider approving a drug, the agency requires duplicated findings in prospective, double-blind, placebo-controlled studies. For Biogen’s aducanumab, there is only one, incomplete, non-robust, barely positive study, which in turn is directly contradicted by an identical, negative second study.
AD is heartbreaking and a public health matter of great importance, and the Biden administrations AD initiative is potentially a good idea if done correctly, but it is not so clear and present danger that we need to swing at it blindly like a piñata, and employ known fallacy-ridden Texas Sharpshooter analyses which still only produced questionable evidence of efficacy.
In so doing, the FDA surreptitiously, unilaterally and non-scientifically declared amyloid beta lowering as an acceptable surrogate marker of AD. That contradicts Biogen’s own findings, on top of ten other clinical trials using drugs which have the same mechanism of action as aducanumab. It doesn’t matter how well a drug is at clearing amyloid; in total, all 23 clinical trials illustrate that it does not lead to clinical benefit, is unsafe, or both.
Stated more bluntly: patients desperate for hope will flock to a drug that risks significant side-effects but is not proven to even slow the progression of dementia (let alone stop AD progression…let lone cure AD), and taxpayers will fund the scamming of vulnerable seniors. FDA officials excluded from the approval process were shocked to discover the corrupt bargain struck by their agency leaders. The FDA’s own statistical analysis directly stated: “there is no convincing evidence of delaying clinical progression, cognitive or functional.”
The independent clinical experts at ICER also did a clinical review of the data and voted unanimously, 15-0, that Aduhelm’s data did not adequately demonstrate that it provided any real benefit compared to existing standard care protocols for an Alzheimer’s patient without the drug. Finally, nearly every single medical op-ed pundit has scolded the FDA’s approval, calling it thinks like “false hope,” “bad medicine,” “disgraceful,” “dangerous” “a disaster” or “a new low.”
Bottom line: The approval of aducanumab is the most hideous in a now established pattern of how the FDA disregards science in favor of pharmaceutical industry-friendly approvals.
Because future FDA decisions treat past approvals as a form of precedent, we would expect up to two dozen other failed Alzheimer’s drug makers to seek Biogen-like resurrections and accelerated approval.
Who exactly is behind the approval of these machinations? Nine months ago several high-level officials at FDA, including then-acting director of FDA’s Center for Drug Evaluation and Research (CDER), Patrizia Cavazzoni, were so troubled that a Trump-appointed FDA commissioner might contradict science and play fast-and-loose with questionable vaccine and hydroxychloroquine approvals, she published an op-ed co-authored by her CDER direct reports. In this piece, they announced, with unabashed arrogance that “when it comes to decisions to authorize or approve the products we regulate, . . . we and our career staff do the best by public health when we are the decision-makers, arriving at those decisions based on our unbiased evaluation of the scientific evidence.”
This unprecedented public “declaration of FDA independence” was drafted and published behind then- FDA Commissioner Stephen Hahn’s back, which may explain why the authors curiously claimed they wrote it as private citizens and not as FDA officials, which is a laughable legal impossibility.
Nine months was a long enough time for Cavazzoni to re-configure her standards, and overrule other scientists at the agency, plus the entire AC of AD experts and the established scientific standard at CDER.
In April, President Biden’s FDA rewarded Cavazzoni for her public attacks on Trump and his appointees at FDA by promoting her to permanent Director of CDER after being at FDA for a mere two years. As CDER director, she is now responsible for overseeing all new drug approvals — and wouldn’t you know it — one of her first major actions was to reverse agency findings and decades of practice to approve a failed drug that just happened to politically benefit her patron Biden’s “War on Alzheimer’s” narrative.
Prior to joining FDA in 2019, Cavazzoni spent nearly two decades all over the pharmaceutical industry (Eli Lilly, Pfizer and Sanofi) as an administrator according to her linkedIn bio — a very atypical career move with likely financial penalties. Cavazzoni’s background is in psychiatry, a specialty famous for not following the rules of evidence-based medicine, unlike the specialties of pharmacology, biochemistry, biostatistics or any of the other hard academic sciences.
During an interview — just days following aducanumab’s approval — Cavazzoni, who is not a neurologist, castigated FDA advisory committees (ACs), as “lacking prominent experts” or “appropriate expertise” ostensibly including the neuroscience AC plus the three members who resigned — Those being: 1) a Mayo Clinic neurologist, 2) a Washington University neurologist and 3) a Harvard epidemiologist-physician professor. Cavazzoni then called for the FDA to partner with industry in playing a role in the operation of selecting AC members. Obviously that suggestion is absurd and would threaten AC objectivity.
Its also obvious that the “Cavazzoni Era” and a debased FDA scientific standard has only just begun.
Following FDA’s contentious approval of aducanumab and at least one secret meeting, Cavazzoni’s 2020 op-ed is at the very least ironic, if not outright hypocritical. Certain other statements made by Cavazzoni (who was listed as primary author) stand out:
· “Our decisions will continue to be guided by the best science… making decisions guided by the best evidence” (note: I’m confused by the use of the word ‘best’ here…)
· “Protecting the public health is our beacon, and sound science is our guide to navigate controversial waters, we stay true to our mission as we fulfill our duty to the public.”
· “…[We] base our decisions in support of our public health mission”
· “If the agency’s credibility is lost because of real or perceived interference, people will not rely on the agency…”
· “…erosion of public trust will leave consumers and patients doubting our recommendations.”
These statements from Cavazzoni and coauthors reveal pharmaceutical-grade hypocrisy. With her approval of aducanumab, Cavazzoni has done exactly what she pledged not to, in writing: approve a drug contrary to unbiased scientific evidence, and allowed political considerations and secret interference to occur.
Time will prove that as the lack of efficacy of aducanumab becomes more evident, public trust in the FDA and the government, will erode.
As we can see by her own article on the matter, Cavazzoni clearly knows what the rules are, and what the right thing to do should be. The problem is: she just doesn’t seem to care. Seeing Cavazzoni’s whole one page justification recommending aducanumab’s approval does absolute zero to quell the sincere concern for scientific integrity her approval has wrought both inside and outside FDA. Even worse: Cavazzoni gave Biogen an outrageous, extended, 2030 deadline until they have to prove the drug actually works, by when hundreds of billions could have been wasted and/or the drug patent will have nearly expired anyhow. Projections for the cost of this drug are between 57.7 to 115.3 billion either of which would up-end Medicare’s finances. If every AD patient in America were to take aducanumab, it would cost over 1/3 of a trillion dollars. For perspective, in 2019, Medicare spending on every single pharmaceutical amounted to “only”183 billion.
Cavazzoni knows that she will not be held accountable for having wasted billions of taxpayer dollars, and is guaranteed her high-paying government position in the same vein as a tenured professor. Despite the overwhelming outrage among nearly every scientist, Biden and his “party of science” hasn’t uttered a word on the matter, illustrating their collaboration, complacency or blind indifference, despite the potential catastrophic cost to Medicare.
Even the unmistakably liberal FDA and drug industry reporting site STAT NEWS which had repeatedly and strategically published articles fawning and gushing over Cavazzoniover the past years to promote her appointment as CDER director is now questioning the validity and logic of the Cavazzoni’s blessing of aducanumab.
Concerned scientists should not expect FDA’s approval to be second-guessed by prescribing physicians; 91 percent of whom reflexively trust that the benefits of FDA-approved therapies outweigh their risks. Physicians will prescribe aducanumab to appease family or patient requests and to profit from taxpayer funded Medicare subsidies they receive for administering the drug.
To be clear, I do not see Acting Commissioner Janet Woodcock as culpable here, as she has the entire FDA to run, including: cosmetics, dentistry, foods, medical devices, radiation, tobacco, all of veterinary medicine, et cetera. This unscientific approval falls squarely upon the recommendation of Cavazzoni, as CDER director, and her staff. I applaud Woodcock’s call for an OIG investigation, but am willing to take bets that it will not yield anything of note, unless the OIG employs specialized FDA medical experts who understand the of complexities of biotechnological drug approval, FDA regulatory affairs, the FDA review process, plus regulatory pharmacology experts who understand the concept of validated vs. unvalidated surrogate biomarkers.
Many including myself, have advocated for independent FDA oversight for over a decade. Normally, it wouldn’t be necessary because scientists ought to be trusted to base their decisions on hard scientific findings, not “optics” or an exuberant rush to fulfill Biden’s campaign promises. And certainly not for the purpose of securing lucrative rewards or private-sector employment following one’s employment at FDA; It is known that 50% of FDA scientists who push a drug through the approvals process are commonly later given jobs at the companies whose drugs they helped approve.
Taxpayers and AD sufferers deserve ethical and science-based drug approvals using the FDA’s established, historical standard. Clearly, aducanumab is not the treatment patients need or should want — at any price. Because of a pattern of rogue, non-science-based decisions such as aducanumab, the FDA now needs independent scientific oversight. That will be the topic of a forthcoming article of mine on Forbes.
Dr. David Gortler is an FDA and healthcare policy scholar at the Ethics and Public Policy Center in Washington DC. He was a professor of pharmacology at the Yale University School of Medicine and FDA Medical Officer who was later appointed to serve on the FDA’s Senior Executive Leadership Team as senior advisor to the FDA Commissioner for: drug safety, FDA science policy and FDA regulatory affairs. He also serves as a consultant at FormerFDA.com