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Lilly Alzheimer’s drug gets unanimous backing of FDA panel

An experimental and closely watched medicine for Alzheimer’s disease is one step closer to approval, after receiving support from a panel of experts who advise the Food and Drug Administration.

On Monday, the panel unanimously voted that the medicine, developed by Eli Lilly and known as donanemab, appears to be an effective treatment for certain Alzheimer’s patients. The experts also concluded, by an 11-0 vote, that the drug’s benefits outweigh its risks, despite some safety concerns.

“I thought the evidence is very strong and the trials [show] the effectiveness of the drug,” said Dean Follman, a panelist and assistant director of biostatistics at the National Institute of Allergy and Infectious Diseases.

Though the FDA isn’t required to follow the recommendations of its advisory committees, it typically does. Should the agency grant approval, donanemab would be the third Alzheimer’s therapy of its kind cleared for the U.S. market. These medicines work by breaking up sticky, toxic collections of “amyloid beta,” a protein many researchers believe to be a root cause of the memory-robbing disease.

Whether Lilly’s drug can avoid the obstacles that have held back its predecessors remains unclear. The first product in this class, Biogen and Eisai’s Aduhelm, was mired in controversy and eventually withdrawn from market. A second, newer option from those companies called Leqembi is faring better commercially. But both Biogen and Eisai acknowledge Leqembi’s launch has been more challenging than they anticipated.

Lilly built its approval application around a placebo-controlled clinical trial that enrolled nearly 1,700 people in early stages of Alzheimer’s disease. The trial found participants who were given donanemab declined 22% slower than those who were in the control group, as measured by a rating scale that combines two well-known scoring systems for evaluating the severity of Alzheimer’s symptoms.

FDA advisers acknowledged the positive results, yet questioned how applicable they would be to the broader Alzheimer’s population. All study participants were in earlier stages of the disease, and most were white.

Additionally, Lilly’s study had unique design elements that made evaluating the results trickier. For example, in order to enroll, participants had to test positive not only for amyloid, but also for another protein tied to the development of Alzheimer’s. The trial found the disease progressed even slower among donanemab-treated patients with low to medium levels of this “tau” protein.

FDA advisers therefore wanted more clarity about the role tau would play in prescribing the drug if it were approved — especially since testing for tau requires PET scans, which can be costly and time-consuming.

“Inclusion of requirements for [tau testing] will further limit the number of patients who can have access to these types of medications,” said Cynthia Carlsson, a panelist and a professor of medicine at the University of Wisconsin School of Medicine and Public Health.

“So it’s a nuanced situation where, on the one hand, we do need to have additional data on the no and very low tau population. And on the other hand, we should not require having [tau testing] for access to this medication.”

Teresa Burrachio, the director of FDA’s neuroscience office, noted early on in the meeting that tau burden wouldn’t necessarily affect the agency’s approval decision, “but could potentially be a consideration for labeling.”

Another distinctive choice Lilly made in running its study was to have participants discontinue donanemab if amyloid levels dropped below a certain threshold. While some panelists described this design as innovative, they still questioned how it would translate to real-world treatment. What would happen, they asked, if amyloid began accumulating again in patients’ brains?

“I love the idea of being able to stop the treatment,” said Colette Johnston, the panel’s patient representative. “But I am concerned about what happens if we’re not following up, and we’re not getting that information once we discontinue the dosing.”

Both FDA staff and panelists were also focused on a type of brain swelling and bleeding, known as ARIA, that occurred in people treated with donanemab and other drugs like it. ARIA is quite often asymptomatic and is only identified via magnetic resonance imaging

But at least two donanemab-treated participants, and possibly a third, died as a result of ARIA episodes, raising questions about the drug’s safety if approved for general use.

Lilly executives said that, later in the trial, they were able to better identify asymptomatic cases by having patients undergo more frequent MRIs. In these people, the company delayed additional drug infusions until brain swelling subsided to prevent it from becoming more serious.

For people at high risk of ARIA, such as those with a genetic marker named APOE4, Lilly executives said they would recommend closer monitoring.

Patients, caregivers and physicians testified at the hearing, almost all of whom asked the committee to recommend an approval. One, a 75-year-old man who participated in Lilly’s trial, said he had an infusion-related side effect that ended with an emergency room visit. Even so, he said he concluded donanemab’s benefits still counterbalanced its risks and decided to remain in the study.

“The community understands that donanemab is not curative, but has shown in promising clinical trials it can delay progression of disease,” Sue Peschin, CEO of the Alliance for Aging Research, said. “This is of key importance to people living with early Alzheimer’s where quality of life outcomes such as cognition, personality, and the ability to care for oneself are the ones that matter most.”

Estimates hold that roughly 6 million to 7 million people in the U.S. have Alzheimer’s. The disease is a leading cause of death, and inflicts an immense physical, mental and emotional toll on patients and their caregivers. It is also extremely expensive. Research published in the American Journal of Managed Care noted how, in 2022, the estimated healthcare costs associated with Alzheimer’s treatment were $321 billion.

For Lilly, approval would cap off a decades-long mission to get an Alzheimer’s medication on the market. The company came somewhat close years ago with a similar drug called solanezumab, though clinical failures led to the therapy getting scrapped.

On Wall Street, analysts expect an approval would add another blockbuster product to Lilly’s portfolio, which has been buoyed by the success of the company’s GLP-1 drug for obesity. As of early March, the average analyst estimate had donanemab generating close to $3 billion in annual sales at its peak, according to the investment firm Jefferies.

Editor’s note: This story has been updated with additional detail from the meeting.