Lecanemab, a new Alzheimer’s drug, could soon get FDA approval. Does it actually work?

A new Alzheimer’s treatment appears to be on the verge of being approved by the US Food and Drug Administration. But that milestone, given the current lack of effective treatments, has been complicated by recent revelations about the FDA’s earlier controversial approval of an Alzheimer’s drug — and the lingering concern among some experts that the hype could once again come out ahead of the science.

The federal agency is expected to make a decision on Friday on whether to grant fast-track approval to lecanemab, an intravenous injection developed by Japanese biopharma company Eisai and American manufacturer Biogen. Faster approval can be granted for new drugs with promising early clinical trial results that address unmet medical needs.

There is reason for optimism, with indications that patients who received the drug in clinical trials experienced less cognitive decline than those who did not. An effective drug would be a boon for more than 6 million people with Alzheimer’s and their families, a breakthrough after decades of false starts and disappointments in finding real treatments to slow the self-destructive disease.

But lecanemab’s search for approval is overshadowed by the previous approval of another Alzheimer’s drug to gain approval quickly: aducanemab, sold as Aduhelm. During the development of aducanemab, clinical trials were stopped at one point because analysts concluded that further investigation was futile: The drug did not work. However, in 2021, the FDA approved the drug over the objections of its own scientific advisors and confused doctors and patients.

The new House report on the drug’s approval, released in late December, revealed how the FDA and Biogen are working together to push the drug to market. Two months after clinical trials were halted in 2019, Biogen executives and senior FDA officials met at a pharmaceutical conference and decided Biogen would move forward with seeking approval. What followed was unusual coordination between private companies and regulators, who met several times to review Biogen’s data and even collaborated on a brief document for the FDA’s scientific advisors who would make the final recommendation on approval.

Usually, in these documents, the opinions of the applicant company and the FDA regulator remain separate. But this time, there are muddled differences, according to the House report, with the FDA instead asking Biogen to insert FDA-drafted language into the company’s part of the report.

“Findings in this report raise serious concerns about the FDA’s lapses in protocol and Biogen’s disregard of efficacy and access in the approval process for Aduhelm,” wrote the House committee. “Criticism of Aduhelm’s approval may have been avoided if the FDA had followed its own internal guidance and practices.”

After the FDA’s scientific adviser pointed out the lack of clear evidence that aducanemab accelerates the development of dementia, as well as signs of serious side effects, Biogen and its FDA partners moved and asked for a faster approval – which has a lower threshold for approval. Biogen only needed to show that the drug reduced the number of amyloid plaques in patients’ brains, not that the reduction caused a decline in cognition. The company and FDA staff are working together to produce a statistical analysis that shows the desired results, although federal officials have previously said they will not use those secondary metrics to approve Alzheimer’s drugs.

Accelerated approval was granted for aducanemab – for which Biogen initially planned to charge $56,000 – in July 2021. But the drug’s momentum after approval quickly slowed. Major health care institutions say they will not prescribe the drug, as there is no empirical support for its effectiveness. Ultimately, Medicare, which had been expected to be the biggest buyer of the drug, said it would generally not cover aducanemab except in clinical trials. That has resulted in minimal patient utilization over the past 18 months.

The approval of this breakthrough treatment is expected to improve the prognosis for Alzheimer’s patients rather than being a major embarrassment for the pharmaceutical company that developed it and the federal regulator that approved it.

Now the FDA is looking into other treatments.

Important differences – and similarities – between lecanemab and aducanemab

The main theory of Alzheimer’s disease, in short, is that the accumulation of amyloid plaques in the brain interferes with normal brain function and causes dementia. But some experts challenge the hypothesis and accuse drug companies and academics of not looking at other ways to try to treat the disease. Lecanemab, a new drug that is about to be approved, and aducanemab are both based on the amyloid hypothesis and target the plaques in hopes of reducing the symptoms of dementia.

The evidence for the effectiveness of lecanemab is stronger than that of aducanemab. The results of the clinical trial were published this week in the New England Journal of Medicine showed that patients given the drug for more than 18 months experienced cognitive decline using a broad measure of dementia compared to patients given a placebo.

That has Eisai, Biogen, and the Alzheimer’s advocacy community optimistic that the FDA will grant approval soon.

“We believe, based on the total positive data from the clinical trials of this treatment, which must be approved by the FDA. The results published by peer-reviewed show that lecanemab will provide patients in the earliest stages of Alzheimer’s more time to participate in daily life and live independently. It may mean months of better understanding of spouses, children and grandchildren,” said Maria Carrillo, the Alzheimer’s Association’s chief science officer, in a statement to CNN.

Some experts ask for caution due to the relatively small size of the measured effect, however, with the editor of Lancet wrote in December that “whether lecanemab is the game changer that some have suggested remains to be seen.”

Like aducanemab, this new drug may be targeted at people in the early stages of the disease. And like aducanemab, there are reports of serious side effects, including some deaths, as science was reported last month, although the exact interaction in the deaths remains unclear.

I asked doctors and social workers who work with Alzheimer’s patients about their perceptions of new drug approvals, especially after the disastrous aducanemab incident. Alison Lynn, director of social work at the Penn Memory Center, said she has heard from excited caregivers and patients.

But clinical staff have concerns. “Our paper seems optimistic about the more promising data on lecanemab, but with caution,” he said. “Some of the concerns from the debacle with Aduhelm remain the same, even with better data.”

Concerns about equitable access are paramount. Will Medicare cover this drug, unlike aducanemab? Otherwise, access could be limited to the very wealthy, as the cost is estimated to be between $9,200 and $35,600 for annual treatment. Ideally, patients would receive a brain scan for amyloid plaques before receiving lecanemab, but the procedure is usually not covered by Medicare and can cost up to $20,000 out of pocket. Patients still have to go to hospital to receive injections every two weeks, which presents another barrier to access for people with dementia.

“What are we going to do when someone has advanced dementia and asks for this drug even though the data only supports its early-stage use?” said Lynn. “Basically, there are concerns about the logistics and ethics of access.”

Approval of a new Alzheimer’s treatment should be cause for celebration. And there is good reason to believe that lecanemab will be more successful than aducanemab.

But recent events also give good reason to be cautious. This is aducanemab’s bad legacy for future Alzheimer’s drugs: It’s a shadow we must escape.