New Alzheimer's drug may have limited real-world impact

Leqembi, a new Alzheimer's drug developed by Eisai and Biogen, may have passed muster with the FDA last week, but experts say it's still an open question how much it will improve the quality of patients' lives.

Why it matters: Patients, doctors and insurers still have to decide whether using the drug to slow the disease's progression is worth the associated hassle, cost and safety risks. These decisions will ultimately decide the overall uptake and commercial success.

Between the lines: Leqembi's accelerated approval was based on data showing patients taking the drug saw a statistically significant reduction in brain amyloid plaque that's thought to contribute to the disease. But data published in November — which was not used for the accelerated approval — found that the drug provides a clinical benefit as well.

• The data, published in the NEJM, found that Lequembi slowed cognitive decline in patients in the early stages of the disease by 27% over 18 months. That will be used to determine whether the drug warrants a full FDA approval.
• But clinicians caution that such a modest benefit may not be very noticeable to patients and comes with significant tradeoffs.
• “We’re still far from an intervention that can really slow down or stop the progression of the disease, but it is very exciting to have something that can be offered probably as part of a series of interventions," said Alvaro Pascual-Leone, a professor of neurology at Harvard Medical School and chief medical officer of Linus Health.

The big picture: Alzheimer's disease is both devastating and common, teeing up a potentially huge market for cures for the more than 6 million Americans who suffer from the condition.

• But the FDA says the treatment should only be initiated in patients with "mild cognitive impairment or mild dementia stage of disease," narrowing the eligible patient population. That translates to about 1.5 million Americans, per the NYT.
• It also requires patients to overcome significant hurdles before starting treatment, including testing to confirm they have a buildup of amyloid and an MRI within the last year. The treatment itself consists of one-hour infusions every two weeks, and patients must receive MRIs throughout the process.
• Leqembi's list price of $26,500 per year doesn't include the cost of these related tests and procedures. For now, Medicare covers the drug and other amyloid-focused cures in limited circumstances, but the agency says barriers will be lowered if the FDA issues a traditional approval of the drug. It's unclear how private payers will approach coverage.
• Finally, the drug poses significant safety risks, like other drugs for serious diseases, and three patients who received Leqembi in a clinical trial died.

What they're saying: Given all the downsides, some providers say they want more information — particularly from the FDA — before they feel comfortable prescribing it to patients.

• "At this moment, based on the available data, I'm not clear and skeptical," said Yale professor Reshma Ramachandran. "I would have a lot of reservation about prescribing this."
• “I do think one of the things that has given us a lot of pause…is the risk and the death issue. Nobody wants to be the clinician that prescribes a drug that could potentially harm our patients," she added.

The other side: "This treatment can change the course of Alzheimer's in a meaningful way for people in the early stages of the disease, allowing more time to participate in daily life and live independently," said Maria Carrillo, chief science officer of the Alzheimer's Association, in a statement on Friday.

• "The decision to use this treatment should lie in the hands of the individual living with the disease and their family, in consultation with their doctor."

What we're watching: The upfront requirements for patients who do want to receive the drug will likely present broad challenges to the health system.

• “There is a lot of changes to the health care system and how we practice that will need to be put in place to really offer this treatment at scale to many patients," Pascual-Leone said.