Reporters uncover conflicts and dubious data on latest Alzheimer’s drug

A blockbuster story in the September 25 issue of The BMJ found major concerns surrounding the approval process, efficacy, and safety of the newest Alzheimer's drug, donanemab (brand name Kisunla).

An analysis by independent investigative journalists Jeanne Lenzer and Shannon Brownlee revealed a lack of transparency, fuzzy math, hidden red flags, and underreporting of deaths from side effects, among other issues that point fingers at both the manufacturer, Eli Lilly, and the FDA, which approved the drug in July for patients with mild cognitive impairment or early-stage Alzheimer's disease.

Journalists can use some of the suggestions Lenzer and Brownlee offer in this tip sheet to conduct similar investigations of drugs or devices. Among their most important tips are to read all briefing and background materials thoroughly because you never know what you might find hidden.

More about donanemab

Donanemab works similarly to other drugs in its class, lecanemab (Leqembi) and aducanumab (Aduhelm), to target the building of amyloid plaque in the brain, which is believed to cause Alzheimer's disease. Biogen subsequently pulled the plug on aducanumab in February, following lecanemab's approval the previous month.

As the BMJ article notes, the benefits of these drugs for a small subset of people, compared with serious and dangerous side effects, including brain bleeds and death, were actually very paltry, once you dig deep into the data. As Lenzer and Brownlee reported, an external review found that drug maker Lilly underreported adverse events such as brain hemorrhage and deaths to the FDA when it first applied for approval.

While the FDA initially pushed back on some of the findings and required the company to conduct a post-market observational study to track adverse events, that data is not due until 2037. Meanwhile, advisory committee members who were critical of the drug were soon off the panel.

Advisory panel replaced

"We found out that they [the FDA] had replaced all of the advisors, and that was a clue right there that this was a serious issue," said Lenzer in a Zoom call. She said she had never heard of this kind of action before. The drug subsequently received accelerated approval by an 11-0 vote of its advisory committee, despite "some concerns" over safety.

Lenzer and Brownlee reported that three of the new advisors who recommended approval of donanemdab received up to $62,000 in direct payments or research funding from Lilly. They also discovered that other advisory committee members had financial ties to Lilly or companies developing similar drugs or tests for Alzheimer's disease.

"The Alzheimer's space has been plagued by overconfidence in understanding the cause of the disease, phony claims about over-the-counter drugs and their benefits, including overhyped claims from pharma about essentially useless and risky drugs," said Arthur Caplan, Ph.D., professor of bioethics and founding head of the division of medical ethics at NYU Grossman school of medicine's department of population health in New York City.

Transparency and vigilance

While critics often argue that the FDA is too slow to approve new drugs, and impeding access to cures, Lenzer and Brownlee said the agency needs to take more, not less care with drug and device approvals.

Caplan, who writes widely on research ethics, said the FDA must be far more vigilant, transparent, and demanding. "People are so vulnerable and fearful that they are easily exploited. Many doctors want to offer hope so their guard is down about prescribing," he said. "While it is understandable, they are abrogating their duties as guardrails."

One additional caveat reporters should bear in mind is to be skeptical when speaking with representatives from many patient advocacy groups. Many of these organizations receive money directly or indirectly from drug or device manufacturers. These companies spend more on patient advocacy groups than they spend lobbying Congress, according to Brownlee.

"They have figured out that the patient advocacy groups can be their covert mouthpieces and these groups have an enormous effect on the FDA, and they're quite powerful," she said. Some groups are fiercely independent but many are not, so do your due diligence before reaching out.

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