One in 10 Americans age 65 and older live with Alzheimer's dementia, but the last time the Food and Drug Administration approved a new drug to treat any of them was about 16 years ago. That drug, Namenda, can ease some of the symptoms of dementia, but there's nothing anyone can do to stop patients from deteriorating.
A recent Washington Post article from Christopher Rowland alleges that Pfizer (NYSE:PFE) executives learned they had a potential new treatment for preventing Alzheimer's disease, but they didn't bother following up because a loss of market exclusivity was just around the corner. Rowland isn't wrong about the loss of exclusivity, but the story ignores a few other reasons the company didn't bother to follow up.
Pfizer has made some bad decisions in the past that should make its shareholders, and the rest of us angry, but this is not one of them. Here are five good reasons Pfizer sat on data suggesting Enbrel, an aging rheumatoid arthritis drug, might also prevent Alzheimer's disease.
1. It doesn't go where it needs to be
Although we really don't know how Alzheimer's begins, we do know that it's a disease of the brain. Getting a drug to travel from the bloodstream and into the brain, though, is a lot harder than you might think.
Enbrel is not a drug that crosses the blood-brain barrier, and it isn't supposed to. That's because it's a big protein that neutralizes tumor necrosis factor (TNF), an important gear in the mechanism that begins the inflammation process associated with rheumatoid arthritis.
Rheumatoid arthritis patients generally exhibit way too much TNF activity, so taking an anti-TNF drug should return all systems to normal and halt the disease. For otherwise healthy patients, though, dialing down their immune systems with an anti-TNF drug can increase the risk of contracting uncontrollable infections. In other words, there's a good chance the FDA would never approve Enbrel, or any drug from this class, as a prophylactic treatment for healthy patients worried about developing Alzheimer's dementia.
2. It's not an eye-opener
Pfizer noticed insurance claim data in 2015 that suggested patients treated with Enbrel were 64% less likely to report Alzheimer's disease years later. Scientists in institutions around the globe were examining the role TNF might play in Alzheimer's disease years before researchers in the immunology department tried to convince management to test Enbrel as a treatment for dementia.
Biopharmaceutical companies have spent untold billions of dollars trying to treat Alzheimer's by targeting plaques of protein fragments that are nearly always present in the brains of people with Alzheimer's and other dementias. Now that it's pretty clear that those plaques are a symptom and not the cause of dementia, however, more drugmakers are listening to scientists who think Alzheimer's is really an inflammatory disease but not enough to plow a lot of money into the concept.
3. Insurance claim observations aren't a great indicator
The trouble all started when an analysis of hundreds of thousands of insurance claims suggested rheumatoid arthritis patients treated with Enbrel were 64% less likely to develop Alzheimer's disease than people who didn't receive Enbrel. Unfortunately, comparing populations that receive a drug with a five-figure annual price tag to populations that don't is problematic, to say the least.
So few associations found in insurance claim data have been repeatable in a controlled clinical trial that they're largely ignored, just like this one was. If they were repeatable more often than not, cancer would have been extinguished from the planet years ago and I'd have a full head of hair. In other words, there's probably another explanation for the observed benefit.
4. Clinical trials are expensive
According to The Washington Post, researchers from the immunology department estimated the cost of running down this lead would only cost $80 million, or around $26,700 per person enrolled in a 3,000-patient study. Unfortunately, that estimate's much lower than the total cost to run a years-long study with thousands of patients.
Clinical trials are generally performed in partnership with hospitals, which are not famous for charging reasonable prices. That means regular visits to receive an Enbrel injection and a battery of efficacy and safety measurements can really add up fast.
Independent data monitors who crunch all the data clinical trials throw off don't work for peanuts, either. While $80 million might be enough to begin a clinical trial with thousands of patients randomized to receive Enbrel or a placebo over the course of several years. Once all is said and done, the company could easily drop a nine-figure sum just conducting a large study.
5. It's not Pfizer's drug
Enbrel originated with a company called Immunex, which had a deal with Wyeth to co-promote the drug in North America and allow Wyeth to market the drug everywhere else. In 2001, Amgen (NASDAQ:AMGN) bought Immunex and eight years later, Pfizer bought Wyeth.
Although Pfizer inherited an exclusive license to market Enbrel outside of North America, Amgen still owns the patents. Unless Alzheimer's disease was one of the certain future indications Wyeth and Immunex agreed to work together on, the ball was in Amgen's court the whole time.
The idea that TNF could play a role in the progression of Alzheimer's disease is old enough to vote. With this in mind, you'd think that companies earning billions with a TNF drug would have noticed and seriously considered the possibility at least a decade ago before deciding against it.
This doesn't have to end here
If you're going to ask senior management at a well-run company to blow at least $80 million on a clinical trial that has almost zero chance of success, you might as well ask them to torpedo their careers. That doesn't mean someone else can't pick up the torch.
The Alzheimer's Association has invested $455 million on nearly 3,000 investigations over the past 37 years. There might not be enough research dollars in the public sector to conduct a trial with thousands of patients, but there are plenty of biosimilar versions of Enbrel available if any organization wants to try a smaller proof-of-concept study on its own.