Could Etanercept, Adalimumab Have Potential to Fight Alzheimer Disease? Critics Say We'll Never Know

Last year, when noted researcher James Allison, PhD, won the Nobel Prize for Physiology or Medicine for his pioneering work that led to the development of groundbreaking oncology treatment, he took the occasion as an opportunity to decry what he said was a death of basic scientific research, as development for new pharmaceuticals is usually tied to closely guarded company data.

This week, The Washington Post reported that etanercept, sold as the blockbuster rheumatoid arthritis drug Enbrel by Amgen within the United States and by Pfizer in other territories, appeared to reduce the risk of Alzheimer disease by 64% when Pfizer researchers analyzed hundreds of thousands of insurance claims. The researchers urged the company to conduct a clinical trial to see if the effect was real, but after several years of discussion, Pfizer opted not to pursue that path, deeming that it held little chance of success.

Both Pfizer and Amgen denied that the decision was tied to commercial reasons; Enbrel has 2 biosimilar products approved (Eticovo and Erelzi), but neither is commercially available due to extensive patent litigation. Erelzi was approved in 2016, and within days after Eticovo’s April approval, Amgen, Hoffman-La Roche, and Immunex sued and alleged infringement of 5 patents.

Some outside scientists interviewed by the newspaper, which obtained confidential company papers detailing the findings and internal discussions, disagreed with the decision, noting that Alzheimer disease has no known treatment and has devastating consequences.

According to the Alzheimer’s Association, without any therapy advances, the disease is expected to cost the country as much as $1.1 trillion by 2050 and affect 15 million people. The bulk of care for this illness is currently borne by unpaid caregivers, currently valued at over $230 billion.

Similar to Allison when he discussed his prize-winning work last September, noting the long struggles he had with T-cell research that eventually led to checkpoint therapy (“You can understand something about a signal by knowing what didn’t happen,” he said), the researchers interviewed by the Post said that without publishing the data publicly or attempting a clinical trial, the scientific and Alzheimer community will not know if the drug truly has potential.

A trial would have cost at least $80 million, according to the report, and would have made little financial sense given the upcoming patent expirations on Enbrel and eventual biosimilar competition.

But researchers increasingly suspect that systemic inflammation holds clues to the inflammation that happens within the brain, and the Pfizer data isn’t the only set pointing to the anti-inflammatory potential of etanercept for Alzheimer. The newspaper noted that a similar study published in 2016 reached a similar conclusion. Exposure to anti—tumor necrosis factor agents like etanercept was associated with a lower risk of the brain disease.

In addition, the Pfizer researchers also found a similar effect when they looked at AbbVie’s innovator adalimumab product Humira, another anti-inflammatory drug enmeshed in patent thickets with approved but currently unmarketed biosimilar adalimumab options.

Enbrel and Humira are the 2 drugs that account for the largest share of drug spending in employer health plans.