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.
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.
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.”
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.’’