A new Alzheimer’s drug has been approved by the US Food and Drug Administration. However, given the current lack of effective treatments, such an important milestone has been complicated by new revelations about the FDA’s earlier controversial approval of an Alzheimer’s drug — and lingering concerns from some experts that the hype could once again be ahead of the science.
The federal agency decided on Friday to grant accelerated approval to lecanemab, an intravenous injection that was developed by the Japanese biopharmaceutical company Eisai and the American manufacturer Biogen. Accelerated approval may be granted to new medicines with promising preliminary clinical trial results that address an unmet medical need.
There’s reason for optimism, with evidence that patients who received the drug in clinical trials experienced less cognitive decline than those who didn’t. An effective drug would be a godsend for the more than 6 million people with Alzheimer’s and their families, a breakthrough after many decades of false starts and frustrations in finding a real treatment to slow the disease’s uniquely devastating deterioration in a person’s sense of self .
But the drive for approval of lecanemab has been overshadowed by the prior approval of another Alzheimer’s drug for accelerated approval: Aducanemab, sold as Aduhelm. At one point during the development of aducanemab, clinical trials were halted because analysts decided that further investigation was futile: the drug wasn’t working. Still, the FDA approved the drug in 2021, despite objections from its own scientific advisors and the confusion of doctors and patients alike.
A recent House of Representatives report on the drug’s approval, released in late December, revealed the extent of the collaboration between the FDA and Biogen to bring the drug to market. Two months after clinical trials were halted in 2019, a Biogen executive and a senior FDA official met at a pharmaceutical conference and decided that Biogen would move forward with the filing for approval. What followed was a highly unusual coordination between a private company and its regulators, who met dozens of times to review Biogen’s data and even collaborated on briefing papers for the FDA’s scientific advisors, who would make a final recommendation on approval.
Typically, the opinions of the applicant company and FDA regulators are kept separate in these documents. But this time, according to the House report, every distinction was muddled, with the FDA even asking Biogen to insert FDA-drafted wording in the company’s section of the report.
“The findings in this report raise serious concerns about FDA protocol errors and Biogen’s disregard for efficacy and accessibility in the approval process for Aduhelm,” the House Committee wrote. “Criticism of the Aduhelm approval could have been avoided if the FDA had followed its own guidance and internal practices.”
After the FDA’s scientific advisers pointed out the lack of clear evidence that aducanemab slows the development of dementia and signs of serious side effects, Biogen and its FDA partners switched gears and instead applied for accelerated approval — which has a lower approval threshold Has. Biogen only had to show that the drug reduced the amount of amyloid plaque in a patient’s brain, not that the reduction actually halted the decline in cognition. Company officials and the FDA worked together to produce a statistical analysis that showed the desired result, although federal officials previously said they would not use such a secondary metric to approve an Alzheimer’s drug.
In July 2021, aducanemab was granted accelerated approval — for which Biogen initially planned to charge $56,000. But the drug’s post-approval momentum quickly slowed. Major healthcare facilities said they would not administer the drug given the lack of empirical support for its effectiveness. Finally, Medicare, which was expected to be the drug’s largest buyer, said it would not generally cover aducanemab except as part of a clinical trial. This has resulted in minimal patient uptake over the past 18 months.
The approval of this breakthrough treatment, which was said to greatly improve the prognosis of Alzheimer’s patients, instead became a major embarrassment for the pharmaceutical company that developed it and the federal agencies that approved it.
But there were other treatments in the pipeline, and the next to come before the FDA was lecanemab.
The important differences – and the similarities – between lecanemab and aducanemab
In short, the leading theory of Alzheimer’s disease was that the accumulation of amyloid plaques in the brain disrupts normal brain functions and leads to its telltale dementia. However, some experts have questioned this hypothesis, accusing drug companies and academia of overlooking other ways to treat the disease. Lecanemab, the newly approved drug, and aducanemab are both based on the so-called amyloid hypothesis and target these plaques in hopes of relieving symptoms of dementia.
The evidence for the effectiveness of lecanemab is stronger than that of aducanemab. The results of its clinical trials, published this week in the New England Journal of Medicine show that the patients given the drug for 18 months experienced less cognitive decline using a broad range of dementia compared to patients given a placebo.
That has left Eisai, Biogen, and the Alzheimer’s advocacy community optimistic that the FDA will eventually sign off on their accelerated approval.
“Based on the body of positive clinical trial data for this treatment, we believe the FDA should approve it. Peer-reviewed, published results show that lecanemab will give patients in the earliest stages of Alzheimer’s disease more time to participate in daily life and live independently. It could mean many more months to acknowledge their spouse, children and grandchildren,” Maria Carrillo, chief science officer of the Alzheimer’s Association, said in a statement to CNN.
However, given the relatively small size of the measured effect, some experts urged caution when editing lancet wrote in December that “whether lecanemab is the game-changer that some have suggested remains to be seen.”
Like aducanemab, this new drug is probably best targeted at people in the early stages of the disease. And as with aducanemab, there have been reports of serious side effects, including a number of fatalities, such as: Science reported last month, although the exact interaction in these deaths remains unclear.
I asked doctors and social workers who work with Alzheimer’s patients about their perception of the new drug’s approval so shortly after the disastrous aducanemab saga. Alison Lynn, director of social work at Penn Memory Center, told me she’d heard from enthusiastic caregivers and patients.
But clinical staff have concerns. “Our documents seem very optimistic about the more promising data on lecanemab, but cautiously,” she said. “Some of the concerns from the Aduhelm debacle remain the same, even with better data.”
Equal access concerns are paramount. Will Medicare Adopt This Drug Unlike Aducanemab? If not, access could be limited to the very wealthy, given an estimated cost of between $9,200 and $35,600 for an annual treatment. Ideally, patients would have a brain scan for amyloid plaque before receiving lecanemab, but this procedure isn’t typically covered by Medicare and can cost up to $20,000 out of pocket. Patients still have to go to a hospital every two weeks to get the injection, creating another barrier to entry for people with dementia.
“What are we going to do if someone with more advanced dementia comes up and asks about this drug when the data really only supports early-stage use?” said Lynn. “Basically, there are concerns about the logistics and ethics of access.”
The approval of a new Alzheimer’s drug should be cause for celebration. And there is good reason to believe that lecanemab will prove more successful than aducanemab.
But recent events also give cause for caution. That’s aducanemab’s unfortunate legacy for future Alzheimer’s drugs: It’s a shadow to escape from.
Update Jan 6 2:25pm ET: This story was updated with the news of the approval of lecanemab.