A new approach
Researchers have spent decades and billions of dollars looking for safe and effective medications to fight Alzheimer’s disease — so far, totally in vain.
The few drugs we do have ease some symptoms of the disease for some patients, but they do not slow its progression, much less reverse or cure it.
The good news is, the costly research has identified potential causes and contributors to the disease, at least giving us targets at which to aim new drugs. Still, it’s been disappointing that treatments that seem to attack these targets have produced no breakthroughs to date.
Enter aducanumab — a monoclonal antibody (the same type of drug as the new Pfizer coronavirus vaccine) that targets the amyloid beta protein that forms plaques in the brains of Alzheimer’s patients and is believed to be a cause of the disease.
Starting in 2017, two nationwide Phase 3 clinical trials were begun by the biotech company Biogen to evaluate aducanumab’s effectiveness.
At an 18-month review, the drug seemed so ineffective that both studies were halted. But a later, closer look at the data from one study suggested the highest dose did have a substantial effect, so the FDA allowed Biogen to resume the study with changes.
This fall, Biogen determined that new data showed the drug brought about statistically significant improvement and sought FDA approval for its sale to the public.
The FDA frequently seeks input from an advisory committee to obtain independent expert advice when there are questions about a drug application. It usually, though not always, follows the committee’s recommendations.
Last month, most members of the committee evaluating aducanumab were not persuaded the drug should be approved. Typically, the FDA requires two solid studies to justify approving a new drug, or one large trial and some smaller ones. The evidence seems thinner in this case. One of the FDA’s own internal reviewers recommended a third study be conducted to confirm effectiveness.
But the FDA’s official position is that the data is “extraordinarily persuasive.”
In fact, there is significant pressure on the FDA from families of patients and advocates like the Alzheimer’s Association to approve aducanumab. After all, it’s the first drug to show any evidence of cognitive benefits in Alzheimer’s patients, and there are millions of Americans with the disease whose families are clamoring for effective treatments.
On the other hand, the drug must be administered intravenously once a month and is expected to be costly. If it benefits only a small portion of patients, but requires great expense on the part of many who will want to give it a try (or, rather, on their insurance companies and Medicare), is the FDA doing its job by approving it now on the limited evidence?
In writing about this, the Washington Post quoted Walid Gellad, director of the University of Pittsburgh’s Center for Pharmaceutical Policy and Prescribing, as saying, “If this were a cheap drug, people would be a lot less worried about it…But there is no mechanism in the United States for drugs to be priced conditionally based on uncertainty about their value.”
That got me to thinking…Why not?
It seems there are currently several possible outcomes to this case. If the FDA unconditionally approves the drug, we’ll have another billion-dollar blockbuster medication on the market, no doubt to be widely prescribed. As a result, we’ll find out over the coming years whether the drug really does work as well as Biogen claims, or is an expensive bust.
Alternatively, if the FDA refuses approval now and requires positive results from another full Phase 3 study, it is likely (from what I’ve read) that Biogen will not throw good money after bad. In fact, turning down aducanumab now might even lead other companies studying treatments against amyloid plaques to give up this line of research.
A 2018 paper by researchers from the Cleveland Clinic and University of Nevada, published in Alzheimer’s & Dementia, pointed out that “the failure rate of AD drug development is 99%; the failure rate of the development of disease-modifying therapies for AD is 100%.”
Furthermore, they found that the total costs of an Alzheimer’s drug development program (including U.S. government support, as in this case) “are estimated at $5.6 billion, and the process takes 13 years from preclinical studies to approval by the FDA.”
In a world with a huge need for new drugs even to help only a fraction of patients, and such high barriers to success, can’t we think creatively about how to make this process work better?
Is our choice really only between approval on the one hand (with huge costs to the public and huge benefits to one drug company) and quashing the whole research process on the other?
What about allowing Biogen to offer the drug for sale conditionally for a few years, at some fixed price deemed to be reasonable, with the requirement that all patients on the drug participate in gathering data on effectiveness? It would resemble a clinical trial, but one where people cannot be refused participation as long as they (or their insurance companies) are willing to help defray the cost.
There would be real-world gathering of evidence (as we always find with new drugs, even after FDA approval), the demand of patients and families would be addressed, and the drug developer wouldn’t have to foot the total bill.
If the results are good, the company could eventually “earn” full FDA approval and the drug could rise to market price. If the results are poor, the evidence would be widely known and the drug pulled from pharmacies.
I, for one, would like to see us split the difference in such a case and see if we can’t find a more affordable and fair way to resolve an impasse over a potentially helpful, much-needed treatment for Alzheimer’s.
