The biggest new hope for a blockbuster drug to cure Alzheimer’s has been mired in controversy ever since it went to market. Critics say it’s a sign of declining standards and conflicts of interest at the FDA. And now, the federal government is set to decide on whether to buy the controversial medicine for Medicare patients. Today, we update a drug that entered the market in one of the most controversial processes ever.
Nine months ago, new hope was offered in the form of the first drug that claims to impact the root cause of the dreaded form of dementia known as Alzheimer’s Disease.
Aducanumab, sold as Aduhelm, is given as an injection every four weeks. But there’s a long shadow that’s loomed over the medicine ever since the FDA gave it the green light.
Sharyl Attkisson: They approved it even though not one of the advisors they had consulted said it should be approved?
Dr. Caleb Alexander: They did.
Dr. Caleb Alexander was one of the FDA advisors who voted against Aducanumab’s approval. He’s an epidemiologist, internist, and professor at the Johns Hopkins Bloomberg School of Public Health.
Dr. Caleb Alexander: The advisory committee — there was near consensus among the advisory panel that there just wasn't the evidence to warrant approval.
Sharyl Attkisson: Did they really want advice from the advisors?
Dr. Caleb Alexander: Well, it's a fair question. And in fact, three advisory committee members of the 10 or 11, or however many were on the committee, three resigned in protest of the FDA's decision.
Much of the controversy centers on the FDA’s overt advocacy of a medicine that had failed miserably during the test phase.
Drugmaker Biogen stopped its two major studies midstream, determining that Aducanumab performed so poorly, it was futile to go on. But within months, Biogen returned to the FDA, claiming to have found some evidence of benefit within the stopped studies. And the FDA enthusiastically endorsed the drug without a single of the completed, large studies normally required.
Dr. Caleb Alexander: I do think that this is really an exceptional setting, not only because of the incredible unmet demand for treatments, but because, in this instance, the FDA's decision making appears to have been at such odds with not just the recommendation of the advisory committee members, but also the recommendations of many other parties.
One of the most disputed entries to market of any drug has been followed by a tumultuous nine months on sale.
Sharyl Attkisson: What's happened in the time since this drug went to market?
Dr. Caleb Alexander: There has been a remarkable concern expressed by many different groups since the product has been approved. There are investigations underway in the U.S. Senate, the House of Representatives, the Office of the Inspector General. The FDA itself has launched an investigation.
There are also questions over promotion of the medicine. The Alzheimer’s Association, consulted for advice by millions of patients and family members, plugs Aduhelm on its website. The doctor featured in a promotional video on the site is a paid consultant and speaker for Biogen who worked on one of the clinical studies. And the Alzheimer’s Association has received about $2.8 million from Biogen and its Japanese partner in recent years.
The Alzheimer’s Association told us the money from Biogen is only a fractional percentage of the group’s total revenue, and that contributions have no impact on decision-making, which is based on science.
Complicating the equation, says Alexander, is not just whether Aduhelm works, but questions about whether it could be dangerous.
Dr. Caleb Alexander: There’s an anecdotal report of someone who died after experiencing brain edema which is a not uncommon side effect of the drug.
At least four deaths among Aduhelm patients have recently been reported, including that of a 75-year old Canadian woman. Biogen told us it hasn’t been able to establish her cause of death, and that the three other fatalities “have not been attributed to treatment with Aduhelm.”
Last November, the American Academy of Neurology issued a blunt statement saying “[Aduhem] is a high-cost drug that was approved by the FDA without convincing evidence of benefits and with known harms” including “Risks of cerebral edema [swelling], hemorrhage [bleeding], and hospitalization.”
The doctors’ group went on to criticize the FDA stating that its “recent decisions indicate a lowering of the standards of scientific evidence used for drug approvals, which will require clinicians to scrutinize approved medications more carefully."
The following month, the British Medical Journal reported that more than 40% of patients in a high dose study of Aducanumab suffered brain swelling or bleeding. Within weeks, the European Medicines Agency (EMA) voted not to approve Aducanumab.
Adding to the concerns, cost is keeping Aduhelm from being widely prescribed. It entered the market as one of the most expensive drugs in existence at $56,000 dollars a year. In January, Biogen cut the price in half to $28,200.
And now, the drug’s biggest potential customer —Medicare— could make or break Aduhelm’s ultimate viability. The federal government is proposing to buy Aduhelm only for the relative few Alzheimer’s patients who enroll in a federally-approved Aduhelm study in a hospital-based outpatient setting.
Biogen declined our interview requests but stands by what their representative said at last year’s FDA advisory meeting.
“Given the totality of the evidence, we can conclude that the benefit risk profile for aducanumab is favorable and potentially prolongs patients' independence by several months, even a few years, as demonstrated in our long term study. This matters for the patients, their loved ones and society.”
Biogen also told us it “believes that patients, in consultation with their physicians, should be free to make informed decisions” about taking Aduhelm, “[p]atient safety is Biogen’s highest priority,” and “the potential benefits continue to outweigh potential risks.”
For all the high hopes, Aduhelm hasn’t become a blockbuster success. At the end of last year, Biogen reported $3 million in revenue for the drug and won’t say how many are taking it, though the money translates to no more than a few dozen patients.
The question is whether Aduhelm will manage a major turnaround or go down in the books as a shot in the dark.
Dr. Caleb Alexander: At the time that it was approved, I told many different parties that many chapters have yet to be written. And we're still only halfway through the book.
Sharyl (on-camera): The FDA told us that the risks of brain swelling or bleeding with Aduhelm are described in the prescribing information. The agency also says it supports and will cooperate with Inspector General reviews of its conduct and processes.