On January 6, 2023, the FDA granted conditional approval to a new Alzheimer’s drug, lecanemab, that will be sold as Leqembi.

Vox carried the original story and included an update on January 6th.

The accelerated approval follows on the heels of a controversy surrounding the FDA’s granting approval to a different Alzeimer’s therapy, aducanemab (Aduhelm).

FDA regulations allow early approval of drugs that treat severe or life-threatening illnesses, show potential through performance in clinical trials, and meet unfulfilled medical needs.

Lecanemab is administered by intravenous injection. Its co-developers are Biogen, a U.S. biotechnology company, and Eisai, a Japanese biopharma.

The reason for being cautiously optimistic stems from clinical trials that showed treatment with lecanemab resulted in less cognitive decline when compared with patients who did not take the drug.

An Unmet Need

For decades, over six million Alzheimer’s patients as well as their families have watched and waited for a treatment that would slow the disease or prevent the inevitable destruction and deterioration.

After conducting several clinical trials, analysts were unable to find a reason to continue their investigation of aducanumab. And yet the drug was approved by the FDA despite objections from its scientific advisors.

A report by House Democrats released in December 2022 documented the cooperation of Biogen and the FDA in pursuing aducanumab’s entry into the market. A meeting took place in 2019 between a Biogen executive and an FDA official. They had met at an industry conference and discussed the possibility of Biogen going forward with its effort to seek FDA approval for aducanemab.

Although this level of communication between regulators and companies appeared to be somewhat unusual, the two men met many times jointly, reviewing Biogen’s data.

This is in contrast to normal procedures where the applicant’s opinions are generally kept separate from the opinions of the FDA.

According to the report by the House, not only was there no distinction, but Biogen was asked by the agency to add a portion of the FDA’s language into Biogen’s written opinion.

The House committee’s evaluation stated that serious concerns were raised with respect to the FDA’s lapse in protocol together with Biogen’s access to the approval process. A further FDA admonishment stated that criticism of aducanemab’s approval may not have occurred if the FDA followed its own guidelines.

Biogen Switched Gears

The scientific advisors for the FDA were unable to find evidence of aducanumab slowing dementia. The advisors were also concerned about the information they received suggesting significant side effects.

At this point, the FDA and Biogen decided to switch gears, and the company would apply to the FDA for Accelerated Approval which has less stringent requirements. Biogen only needed evidence that aducanumab could reduce amyloid plaque rather than prevent the decline of patients’ cognition.

The FDA staff and the company joined forces and achieved their intended results despite FDA officials voicing their intention to the contrary. Aducanemab subsequently received the approval.

Initially, a $56,000 cost was envisioned for the drug. However, major healthcare systems refused to use the drug. Medicare, potentially a large purchaser, would only cover aducanemab in clinical trials. Thus, this supposed breakthrough therapy ended up as an embarrassment for the biotechnology company and federal regulators.

Lecanemab vs. Aducanemab

For decades the focus of Alzheimer’s drug research has been on amyloid plaques disrupting brain function and leading to dementia.

More recently some scientists have developed a different theory while at the same time suggesting that academia and drug companies have overlooked possible avenues in attempting to treat Alzheimer’s disease.

Lecanemab and aducanemab both follow the amyloid plaque theory. However, results of lecanemab’s clinical trials, which were published in this week’s NEJM, found that patients who had received lecanemab for eighteen months had less cognitive decline than patients who received a placebo.

These findings were followed by published results showing clearly that lecanemab is effective in early Alzheimer’s. Yet it is understandable that some experts would still advise caution.

The reason for skepticism is that severe side effects as well as deaths have been reported. However, the exact cause of the deaths is unclear.

Questions Yet to be Answered

Will Medicare cover lecanemab? If not, the drug will be a medicine for the wealthy with an estimated cost of $26,500 per year for the average patient. The drug should be commercially available by January 23, 2023.

The usual procedure begins with a brain scan looking for amyloid plaque prior to receiving lecanemab. The brain scan is usually not covered by Medicare and may cost up to $20,000 out of pocket. Patients would be required to be hospitalized every two weeks when receiving the injection.

Nonetheless, there are still those who are enthused about lecanemab and support its approval.