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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 The first product in this class, Biogen and Eisai’s Aduhelm, was mired in controversy and eventually withdrawn from market.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.”


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