The media finally finds the outrage button on costly new Alzheimer’s drug

The story about the new drug to treat Alzheimer’s disease, aducanumab, is as much about the Food and Drug Administration and the future safety of drugs Americans take as it is about one medication that may do little to delay the progression of a dreaded disease.

Normally, when new drugs and devices come to market, the public assumes they are safe because the FDA has offered its blessing. When problems later arise, as they did with the pain medicine Vioxx, eventually withdrawn because it caused heart attacks and strokes, or with medical devices like the hernia mesh, the damage has already been done. This time, though, was different. The outcry over aducanumab’s path to market, along with the FDA’s controversial approval, was swift. The media, the medical community, and academic drug experts have all quickly questioned the FDA’s approval process — a rare occurrence in the world of new drugs.

The national media captured the divide as soon as the FDA approval came down, with a New York Times headline noting “F.D.A. Approves Alzheimer’s Drug Despite Fierce Debate Over Whether It Works,” while The Washington Post told readers: “Alzheimer’s drug sparks emotional battle as FDA nears deadline on whether to approve.” A New Yorker headline was even tougher: “The F.D.A.’s Extraordinary Approval of a Questionable Treatment for Alzheimer’s.”

Why the change in the way the media greeted the new pharmaceutical? After all, this drug was predictably hailed by the Alzheimer’s Association as a “victory for people living with Alzheimer’s and their families,” and one that “ushers in a new era in Alzheimer’s treatment and research?” Glowing statements are common from patient advocates when new drugs hit the market, so it was hardly surprising when the Association announced it “enthusiastically welcomes” the drug’s “historic FDA approval.” 

The drug’s approval may indeed be historic, but not necessarily in the way the patient advocacy group intended. We don’t know whether Alzheimer’s patients and their families saw lent more credence to the Association’s predictably glowing comments or the flood of negative press coverage and warning flags waved by well-known and knowledgeable academics. The latter ranged from Dr. Aaron Kesselheim, a professor of medicine at Harvard Medical School and a member of the FDA’s advisory committee for drugs, who along with two other members resigned in protest of the drug’s approval, to Dr. Michael Carome, director of Public Citizen’s Health Research Group. Carome sent an eight-page letter to the Secretary of Health and Human Services Xavier Becerra blasting the FDA’s decision to approve the drug, writing that the agency’s “non-evidence-based decision to approve aducanumab ultimately represents the pinnacle of the agency’s egregious disregard for science.”

The media, the medical community, and academic drug experts have all quickly questioned the FDA’s approval process — a rare occurrence in the world of new drugs.

Other experts weighed in too. On CNN’s website, Yale professor of medicine Dr. Joseph Ross and Reshma Ramachandran, a clinical scholar physician-fellow at Yale, noted that approval of the drug has “unleashed a perilous precedent that could usher in the approval of countless, costly treatments of uncertain benefit and even harm.” Law professors Nicholas Bagley and Rachel Sachs wrote in The Atlantic that approval of the drug “is likely to increase the federal deficit, squeeze state budgets and force additional costs onto seniors all for a drug that may not work.” As STAT explained this week, if every senior with Alzheimer’s took the drug, it would cost $334.5 billion — that’s half the budget of the entire U.S. Department of Defense. The implications for Medicare spending are staggering.

So, what’s behind this unprecedented outrage at the approval of a new drug?

The drug developed by Biogen and marketed under the name Aduhelm only underwent testing on patients with early or mild cognitive impairment, a major flaw drug experts said. The public needs to know if the drug works for patients who have more severe forms of the disease, yet the regulators approved the drug for all types of Alzheimer’s disease. Carome wrote that approving the drug for all Alzheimer’s patients “defied reason” since patients with moderate or severe disease “plausibly could be more susceptible to the adverse brain effects caused by the drug than patients with mild Alzheimer’s disease.”

When the drug was being tested, Biogen found discrepancies between the trials it was conducting. Patients in one trial given the highest dose of the drug had statistically significant improvement on a clinical dementia scale, while the same patients in another group did no better than patients taking a placebo on the same measure. The trials were stopped early because both failed a “futility” analysis, that is, the chances of any clinical benefit were very small if the study continued to the planned conclusion. Then Biogen reanalyzed the data, and the FDA approved the drug on the basis of the new numbers. “The side effects of the proposed dose included localized brain swelling in 35% of the trial participants and microhemorrhages in 20%,” explained Joel Permutter, a member of the FDA advisory committee who has since resigned in protest of the approval.

The FDA has given Biogen nine years to do further study to see if the drug really works. The drug is likely to be a financial winner for the company, and will bring in a projected $56 billion for treating one million patients in the first year alone. Its financial effects on public health programs — a lot of Alzheimer’s patients will be eager to receive this incredibly expensive drug — like Medicare and Medicaid are likely to be disastrous during the nine-year wait to further evaluate if the drug works or not. “This is one of the most irresponsible and egregious decisions the agency has made in its history,” Carome told me. “It sets a new low bar for approving new drugs. We have regulatory capture. The industry has captured the regulation.”

The path to regulatory capture began some 30 years ago when Congress passed the the Prescription Drug User Fee Act (PDUFA), which gave pharmaceutical companies the green light to help fund the FDA’s work in an order to speed up its review process. Today 65% of the agency’s budget to regulate drugs used for humans comes from the industry. In 1997 came another law, the FDA Modernization Act, which as I reported in my book “Slanting the Story that Forces That Shape the News,” loosened regulation of the pharmaceutical industry and makers of medical devices through a campaign waged by right-wing think tanks. Among the changes the law called for was reducing the number of clinical trials necessary for approval from two or more to one or more, with the goal of bringing drugs to market more quickly. Then in late 2016 Congress passed the 21st Century Cures Act, which loosened regulations even more, a huge step backward as I reported at the time. Once again, the media took a pass on deeper reporting on what Congress and the industry lobbyists had in mind for drug regulation.

“This is one of the most irresponsible and egregious decisions the agency has made in its history,” Dr. Michael Carome, director of Public Citizen’s Health Research Group, told me. “It sets a new low bar for approving new drugs. We have regulatory capture. The industry has captured the regulation.”

Putting all this history in perspective means that the negative press the FDA has received over the super-expensive Alzheimer’s drug is a very big deal. At last the media are showing skepticism about a new pharmaceutical. Contrast the coverage of aducanumab with media attention several years ago when another new Alzheimer’s drug, Aricept, came to market. Even though the New England Journal of Medicine at the time concluded that the drug did not slow the progression of Alzheimer’s disease after three years of treatment and maybe “had a little bit of an effect,” ABC News focused on the shred of positive news. ABC’s physician-reporter recommended that people with pre-Alzheimer’s disease take the drug even though “the study did not support such a clear-cut recommendation.” Aricept is still being used, but Yale’s Ross told me, “It may not be tremendously effective, but it is relatively safe and patients are willing to try it in the hope that it might work.”

Will the same thing happen with Aduhelm?

Ross is skeptical that the process of how new drugs are approved will change very much. “The trends at the FDA are larger than any individual and are reflective of what Congress and patient advocates want to see — more approvals and products reaching the market faster,” he says. “There have been very few lawmakers questioning approval of these products. Most of the questions from Congressional people are about its price.” Companies will continue to bring products to the market using the same approach Biogen used with Adulhelm. “It’s going to be difficult to walk this back.”

Veteran health care journalist Trudy Lieberman is a contributing editor at the Center for Health Journalism Digital and a regular contributor to the Remaking Health Care column.