In 2015, drug manufacturer Pfizer discovered that their drug Enbrel (etanercept), an anti-inflammatory used to treat rheumatoid arthritis, appeared to lower the risk of Alzheimer’s disease by a whopping 64 percent. No one ever learned about this discovery, however, because the company chose not to pursue any further investigation and decided not to release the findings. This comes from an investigative report released on Tuesday by The Washington Post.
Pfizer uncovered Enbrel’s potential for preventing Alzheimer’s during an analysis of hundreds of thousands insurance claims. Company documents obtained by The Washington Post state, “Enbrel could potentially safely prevent, treat and slow progression of Alzheimer’s disease.’’ However, figuring out if the drug would actually have that effect in people at risk of the disease would require an $80 million clinical trial.
Related: Researchers To Test New Alzheimer’s Drug Targeting Inflammation in Humans
Why Didn’t Pfizer Release Its Findings About Enbrel — and Did They Have a Moral Obligation?
After three years of internal debate, Pfizer decided against the trial, despite recommendations from researchers in the company’s division of inflammation and immunology. They also decided to keep their findings mum.
The company’s official stance today is that clinical trials weren’t likely to succeed because the molecules of the drug are too large to reach the brain. And the decision not to release their finding? Pfizer didn’t want to send outside researchers down a dead-end path.
This raises ethical questions about whether Pfizer had a responsibility to release this information to the scientific community. Alzheimer’s is, after all, a disease with at least 500,000 new diagnoses a year. While some experts say, yes, they absolutely should release those findings, others in the field of healthcare ethics claim that disclosures should be limited to information from clinical trials.
The other question that arises: Did Pfizer choose not to pursue a clinical trial due to the fact that Enbrel’s patent would soon be expiring? Enbrel’s 20-year patent has since ended, making way for generic versions of the drug. This means there was no financial incentive for Pfizer to pursue a long, costly clinical trial when profits from the drug would soon shrink to a trickle.
Former anonymous Pfizer executives told The Post that a clinical trial made no business sense. “It probably was high risk, very costly, very long-term drug development that was off-strategy,’’ the former executive explained.
Why Enbrel May Hold Key to Alzheimer’s Prevention
After several recent failures of drugs targeting beta-amyloid plaques in the brain, Alzheimer’s research is taking a renewed interest in the link between inflammation and the disease.
Related: Does Aspirin Prevent Alzheimer’s? New Evidence for NSAIDs
Rheumatoid arthritis (RA) is an autoimmune disease triggered in part by widespread inflammation in the body, driven in part by tumor necrosis factor-alpha, or TNF-a, a protein that promotes inflammation. This immune-related gene also plays a role in the development of Alzheimer’s disease.
A 2016 study in CNS Drugs written by lead author Richard Chou, MD, PhD, found that in people over 65, Alzheimer’s disease is more than twice as common in people with RA than in people without it, but the relationship between Alzheimer’s disease and rheumatoid arthritis is still unknown.
That same year, Chou and his team of researchers at Dartmouth and Harvard made the same discovery that Pfizer had – that patients treated with Enbrel (etanercept) showed a significantly reduced risk for Alzheimer’s disease. Patients treated with five other rheumatoid arthritis drugs did not show any reduced risk. Like Pfizer, they uncovered it by analyzing data from insurance claims.
At that time, Chou had told The New York Times that it was too soon to think of using Enbrel as an Alzheimer’s treatment. “We’ve identified a process in the brain, and if you can control this process with etanercept, you may be able to control Alzheimer’s, but we need clinical trials to prove and confirm it.”
Related: How Alzheimer’s Brain Inflammation Plays a Role in the Development of the Disease
Should You Start Taking Enbrel for Alzheimer’s? What the Science Says
By the time Pfizer had landed on its discovery, a pilot trial using etanercept on Alzheimer’s patients had already been conducted, with promising though controversial results.
In 2006, this small pilot study published in Medscape General Medicine had found that injecting etanercept into the spines of “probable Alzheimer’s patients” resulted in “sustained cognitive improvement.” It involved 15 patients treated weekly for six months.
A follow-up single case study a year later in the Journal of Neuroinflammation reported one patient’s rapid cognitive improvement within minutes of his Enbrel injection. One week later, his cognition skills were still markedly approved.
The author of both studies is Edward Tobinick, MD, an internist who continues to use Enbrel for this and other off-label uses at his clinics in California and Florida. According to the website ScienceBasedMedicine.org, however, Tobinick’s studies are weak at best, due to design flaws and Tobinick’s lack of expertise in the field of neurology.
No other studies using the spinal injection of Enbrel on Alzheimer’s patients have been conducted to confirm Tobinick’s findings.
In 2015, while Pfizer was making its discovery, one double-blind, randomized, placebo-controlled trial using Enbrel for Alzheimer’s was being published in the journal Neurology. It was conducted by Clive Holmes, a professor of biological psychiatry at the University of Southampton in Great Britain, and Pfizer had supported the research.
For Holmes’ study, 41 patients received injections beneath the skin instead of in the spine once a week for 24 weeks. Half received placebos, the rest received etanercept. Researchers concluded that “while there were some interesting trends that favored etanercept, there were no statistically significant changes in cognition, behavior, or global function.” While the findings were inconclusive, the research team recommended that a larger study be conducted.
From these existing studies, there is not enough evidence at this time to use Enbrel off-label to treat Alzheimer’s.
According to The Post, Holmes is one of the few researchers who has gained access to the Pfizer data. He was given the permission to use it in a grant application for a small clinical trial he is currently undertaking in England.
“I’m frustrated myself really by the whole thing,’’ he told The Post, regarding their decision not to pursue research around their drug. “If it’s true in reality, if you did it in a clinical trial setting, it’s massive — it would be huge,’’ Holmes said. “That’s why it’s so exciting.’’
You can read The Washington Post’s investigation in full here.
My wife was in the 3rd Clinical TriAL BY BIOGEN when it was canceled recently. Dr Marks located in Plymouth directed that effort Since 2015 . Iwould life you to send me any information
that would allow her to be treated from other sources.
My sweet, loving mother died with Alzheimer’s disease and the devastating effects. I would love to see this disease conquered NOW!! If there was potentially a treatment and NO ONE THOUGHT IT WAS IMPORTANT TO PURSUE IT THEY SHOULD BE PUNISHED, FIRED OR WHATEVER IS NECESSARY INCLUDING PROSECUTION!!! HOW DARE THEY PLAY WITH PEOPLE’S LIVES??? THIS IS ABSOLUTELY DISGUSTING. ANYONE WHO PLAYED ANY PART IN THIS HORRIFYING DECISION SHOULD BE HELD ACCOUNTABLE IMMEDIATELY.
This makes me angry, outraged, upset, very sad.
HOW DARE YOU PLAY “GOD” WITH PRECIOUS LIVES???
100% with you, JoEllen. I worked in highly competitive corporations for many years, and never saw such an unethical behavior. Prosecution is needed!!
This made me very angry. I lost my mother to this disease. I am in the early stages of this disease. It’s not right or fair. How dare you take hope away from all the people who suffer from this. Just because the patent for the drug was expiring and did expire your executives deemed it not plausible or profitable to do clinical trials. Your drug company exists because of research and clinical trials. You are playing God with people’s lives. How dare you. You don’t think people want to remember their families and friends and whoever or whatever. THIS is very UNFAIR. It will happen to those same executives one day. The LORD DON’T LIKE UGLY.
Yes, the reason was financial. They did not want to pay for the clinical trials to use Embril for Alzheimer’s Tx. They knew once the info was out, that competitors would just wait for the drug’s original patent to expire, then market it themselves , as generic equiv., as soon as the clinical trials that Pfizer paid for were complete.
Alzheimer’s in my family is an epidemic please get this going and done I’m at the age where I believe am demonstrating symptoms at the age of 52 please please get this done
Ha, did you actually use the terminology “moral obligation” with a drug company? Funny / Sad
I want to be included
I lost a mother, aunt and grandmother to AD! ANY ray of hope, regardless of the perceived insignificance, should be made available to independent organizations that might be willing to take the chance on additional trials. these are desperate times!!
what can I do to express my disgust and outrage?
My aunt passed from Parkinson’s, my MOM passed with Alzheimer’s. Now my cousin has been diagnosed. I think I am showing early signs.
This is so egregious I have no words. The decision-makers in this case should hope their own loved ones never suffer from Alzheimer’s or they will truly know they have put themselves in a hell of their own making.
Alzheimers is so terrible that Pfizer should make any possible information that might be
a help is published immediately. !!!!!!!! Pfizer’s management should be called to
testify to Congress immediately and should be condemned for not bringing the
possibility to the attention of all researchers in the world. Is Pfizer management
not human?
I would like to be included if there is a trial. I suffer from osteoporosis and arthritis and family members have dementia.
This is both awesome and awful. Pfizer has an opportunity to be heroes for mankind. I guess the bottom line is blurring their vision
*sigh*
Patents don’t work this way.
If Pfizer discovered a NEW effect for one of their drugs they could secure a patent for that use of that drug for that purpose.
Consider Viagra. The original drug, sildenafil citrate, was patented for a specific use.
You could buy that drug for THAT use in generic form, but you could not buy the drug
for the purpose of ED from anyone else, at least not without some effort from your doctor.
docs can ALWAYS prescribe “off label”…now, your insurance covering for that off label use…well, that’s where the “effort” might lie. if you can pay out of pocket, no problem.
As a bit of perspective on the issue of Embrel, an anti-inflammatory, on Alzheimer’s disease (AD).
First, any allusion that this drug might “prevent” AD should be viewed as a major spin. An inflammatory substance may serve as a palliative to inflammation, and this is definitely one of the downstream effects seen with AD. But there is no basis or evidence that this drug can prevent Alzheimer’s disease. Inflammation is seen with the brains’ immune system activation that occurs in response to Alzheimer’s disease process. Missing is the cause of the AD disease process. Evidence suggests that prime suspect is the chronic, progressive lack of energy (neuroenergetic deficit) in the brain (and central nervous system). This occurs because the blood brain barrier fails to allow sufficient energy to cross from the blood to the brain to provide the energy required for normal brain functionality. The body reacts by initiating its defenses, which includes the inflammatory process, all in the (misguided) hope that this will eliminate the element(s) causing the energy drain. It is also critical to understand that this inflammation effectively drains even more energy from the already-deficient brain, so anti-inflammatory substances and even anti-oxidants would be expected to slow that element of energy drain from the disease process. (So in that case it may, indeed have some short term palliative effect.)
Studies have found decreased progression (again it a decrease, not a stoppage or reversal) with others anti-inflammatory substances, including NSAIDS and anti-inflammatory/antioxidants, such as curcumin (turmeric) – recall the Being Patient discussions with Rudi Tanzi of Harvard. The key we all seek is an understanding of the foundational elements of the Alzheimer’s disease process – what makes it begin and happen – not to give inordinate attention to slowing downstream effects of that process. It would be expected that we will continue to see disappointments with drugs and approaches that focus on downstream effects. Until that understanding is embraced by the greater scientific community, the best approaches remain a focus on reducing all the co-morbidities (obesity, hypertension, diabetes, cardiovascular disease), and adopting a healthful diet and active lifestyle. We WILL soon gain the upper hand on an understanding of the AD disease process, but this is the most hopeful approach at present.
We have been a part of 2 clinical trials for AD and are on the National database of AD patients. We definitely would want to be included in any trial that shows potential for ending this devastating disease or preventing others from succumbing to it.
I have been Diagnosed Having Alzheimer’s I am only 68 it runs in my family. Any thing you can send me would be Helpful
Dale Bredesen, MD, a neurologist who has studied Alzheimer’s disease for several decades, has devised a set of protocols which can delay, and in some cases reverse, the progression of the Alzheimer’s disease. It is all described in his excellent book, “THE END OF ALZHEIMER’S”. You can find more information on youtube and from googling.
A patent was recently issued to a small biotech firm for a drug that was able to breech the blood/brain barrier for treating Alzheimer’s. Could Enbrel be involved?