On June 7, the U.S. Food and Drug Administration (FDA) approved a new treatment for Alzheimer’s Disease (AD), its first in nearly two decades. Manufactured by Biogen (a biotech company based in Cambridge, MA) and called Aduhelm, the drug was supposed to become a cause of celebration by millions of Americans diagnosed with AD. Instead, the Aduhelm approval may well be remembered as the most controversial, if not scandalous, FDA’s decision in the 115 years of its history.

A nasty disease

Let’s first refresh what we know about AD, a truly nasty disease. It is a progressive neurodegenerative disorder that destroys memory, abstract thinking, and cognitive function. It’s the most common cause of dementia in humans (60-80% of all cases), affecting as many as six million Americans and being the sixth leading cause of death.

The risk of getting affected by AD doubles every five years after the age of 65, meaning that with 10,000 baby boomers turning 65 every day, the number of Americans with AD may reach 14 million by 2050.

So far, there has been no real AD cure. Five drugs that were approved in the U.S. for AD treatment, the last one in 2004, can only offer a brief respite from some symptoms in some patients. Worse, the development of AD therapies had been a total disaster: over the period of 2002-2012, 244 drug candidates have been tested in 413 clinical trials, but only one has been approved. This is a 0.4% success rate–or, if you prefer, a 99.6% failure.

A questionable clinical data

Not surprisingly, the results of two Biogen’s clinical trials assessing Aduhelm were eagerly expected—and they were a clear disappointment, yet again. In fact, the trials were halted in 2019 as data showed that Aduhelm provided no benefit to patients’ cognitive function. Moreover, the drug wasn’t even sufficiently safe: approximately 40% of the patients experienced brain swelling and hemorrhaging.

However, Biogen plowed on. The company conducted another analysis of the same data and found that at high doses, Aduhelm showed a 22% reduction in cognitive decline. Encouraged by this newly discovered interpretation, Biogen applied to the FDA for approval.

A controversial approval

An advisory committee convened by the FDA to review the application was almost anonymous in its rejection of Aduhelm: 10 of the 11 experts on the panel opined that that clinical data did not support the approval of the drug (the 11th panelist voted “uncertain.”).

While the FDA is not formally required to follow the advisory committee’s recommendations, it usually does so, especially with the vote count like this one. So it was obviously a great surprise when referring to the extreme need for an AD treatment, the FDA has still decided to approve Aduhelm. In protest, three members of the advisory committee have resigned.

A shocking price tag

And then came another shock, this time in the form of the price tag. Biogen announced that the Aduhelm treatment would be priced at $56,000 annually (not including costs for additional testing and scans patients would need). Given that initially, the FDA set no limits on who will be treated with the drug—and given the number of AD patients in the U.S.–the projected cost of Aduhelm only for Medicare was estimated to be about $57 billion per year, which is more than Medicare Part B spends on all other drugs combined. 

A quick fallout

It was at this point that the pendulum began swinging back. A couple of weeks later, the FDA issued a revised guidance for using the drug, recommending it to be used not by all AD patients, but only by those with mild symptoms. With this restriction, only two million Americans would be eligible for the treatment.

And then, the omnipresent New Your Times published an article describing a cozy huddling of the FDA officials with Biogen’s representatives during the approval process. What initially looked as an example of the FDA’s incompetence suddenly began smelling as something potentially more sinister. At the end of June, two congressional committees launched reviews into the Aduhelm approval process.

It’s vitally important to get to the bottom of what happened behind the FDA’s walls during the approval process. I personally would also be very interested to know what role, if any, was played by so-called patient groups like the Alzheimer’s Association, the largest non-profit funder of AD research.

In the name of the patient

One of the most popular recent trends in healthcare is the drive to what some call “consumer-centric healthcare.” Among many other things this term implies a greater patient involvement in every step of the healthcare delivery process.

The emphasis on patients’ needs has triggered the rapid proliferation of activist groups calling for patients taking a more active role in important healthcare decisions. While any attempts to listen to the proverbial voice of the customer can only be welcomed—be it healthcare or any other customer-oriented industry—one ought to remember that the history of patient group involvement in healthcare decision making process is not without controversy.

Back in the 1980s, the outbreak of AIDS brought to life a voiceful and influential advocacy on behalf of AIDS patients. Having launched an unprecedented in its magnitude public campaign, the AIDS patient advocates succeeded in persuading the U.S. policymakers to shift substantial amounts of NIH funds to HIV/AIDS research. The powerful infusion of taxpayers’ money helped rapidly identify the origin of the HIV/AIDS epidemics and then develop life-saving treatments.

Yet many critics complained that by receiving the amount of NIH funds that wasn’t commensurate with the number of HIV/AIDS patients, the program had siphoned much needed resources away from other, more important, public health needs.

It appears that the case of AIDS is hardly exceptional. In fact, it points to a general trend: various patient groups actively influencing federal funding in favor of “their” diseases.

A 2012 study conducted by Rachel Kahn Best from University of Michigan follows how disease advocacy organizations lobbied Congress for a greater share of NIH funding. Using data on 53 diseases over 19 years, Kahn Best showed that for each $1,000 spent on lobbying for a specific disease, there was an associated $25,000 increase in research funds for this disease the following year.

What is wrong with that, one might ask? Well, the problem is that the amount of NIH funds allocated for any particular disease is being determined not by some objective parameters associated with this disease—for example, by the so-called burden of disease–but rather by the strength of a corresponding patient advocacy group and the amount of money it spends on lobbying members of Congress.

Predictably enough, when you have winners, you have losers, too. Kahn Best points out that diseases affecting primarily women (except for breast cancer) and African Americans tend to receive lower levels of funding because of weaker lobbying.

Besides, adequate funding isn’t provided to so-called stigmatized diseases, such as lung and liver cancer, associated with patients’ “bad behavior” (smoking for lung cancer and alcohol consumption for liver cancer). Year after year, both diseases received smaller funding than would have been predicted based solely on patient mortality.

While welcoming public involvement in healthcare decisions, we ought to find ways restricting the influence of special interests—and money they bring along—on the healthcare decision making process. I know, I know.

A boomerang drug

I’m sure that the Aduhelm approval was considered by many FDA folks as a winning shot at improving the badly damaged reputation of the agency. Instead, Aduhelm became a boomerang drug of sorts adding insult to injury.

Calls to reform the FDA become louder. Can it be reformed?

Image credit: https://asia.nikkei.com/Business/Pharmaceuticals/Eisai-Biogen-Alzheimer-s-drug-set-for-use-at-300-plus-US-hospitals-exec