Editor’s Note: Dr. Lawrence S. Honig is a neurologist at NewYork-Presbyterian/Columbia University Irving Medical Center. He is a professor of neurology at the Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, and the Gertrude H. Sergievsky Center, where he directs the New York State funded Center of Excellence for Alzheimer’s Disease. Honig was an investigator for the study that led to the FDA’s approval of Leqembi and has been an investigator for, received research funding from, and consulted for Eisai, the pharmaceutical company developing lecanemab, and other pharmaceutical companies. The opinions expressed in this commentary are his own. View more opinion on CNN.
In early July, the US Food and Drug Administration granted traditional full approval of Leqembi (lecanemab-irmb) for the treatment of Alzheimer’s disease (AD). This is the first approved medication proven to slow the progression of AD’s clinical symptoms. A phase three trial among 50- to 90-year-old patients with early AD showed that it can do so by about 27% over an 18-month period. While we cannot extrapolate beyond 18 months, this represents about a six-month delay in progression of AD symptoms.
The drug functions by removing the amyloid beta protein that accumulates in the form of plaques in the brains of people with AD. A second disease-slowing drug, donanemab, has recently shown similar effects and may get FDA approval by the end of the year.
The development of Leqembi, building on two decades of research, is a notable success for medical science in that a disease previously impervious to any disease-modifying medical intervention now has an available, effective treatment. However, paraphrasing Winston Churchill, this is not the beginning of the end but the end of the beginning. The drug does not reverse disease symptoms or prevent progression, it slows progression. And there are considerations that make it inappropriate for many patients with AD.
It does, however, lay the groundwork for future AD medications that could alleviate suffering from this devastating disease for generations to come.
Who benefits from this breakthrough?
Leqembi is appropriate for people with Alzheimer’s disease who have “early AD,” defined as mild cognitive impairment due to AD or mild dementia due to AD.
This is the biggest limitation of this drug. While it is possible that people with more advanced Alzheimer’s disease could benefit from Leqembi, we don’t know whether it is safe or effective at these more advanced disease stages. Also, presence of AD must be confirmed by a measure of the beta-amyloid protein in their spinal fluid, by brain PET scan or possibly in the near future by blood tests.
Because of the drug’s side effects, it requires periodic MRI scans, so only people capable of getting an MRI are eligible for this treatment. What’s more, this drug may be riskier for people with certain genetic variations or health conditions so, while the demand for the drug may be great, the suitable population for treatment is smaller.
Who can access this drug?
An important factor for new drugs is their cost. Leqembi’s price tag is $26,500 per year — much more than the current symptomatic medications for AD but comparable or less expensive than new medications for other conditions, for example multiple sclerosis or ALS.
Medicare has announced that it will provide coverage for this medication, although it is requiring that physicians perform certain clinical measures and enter the patient’s data in a registry in order for the drug to be covered, which will increase physician and patient burdens.
What’s more, traditional Medicare only covers 80% of outpatient costs, so for those patients who do not have supplemental insurance, a 20% copay for the drug and required MRI scans might amount to up to $10,000 or more per year out of pocket, but still only a fraction of the cost of a year of in a nursing home.
Still, these costs raise concerns over the availability of Leqembi to underinsured or other disadvantaged groups. Other limitations of access may relate to availability of local neurological specialists, infusion centers and MRI imaging centers.
Are the benefits worth the side effects?
Before taking any drug, you have to consider the possible side effects. For Leqembi, they can include fever and flu-like symptoms associated with the infusion process, which are usually mild, but have occurred in about a quarter of patients.
The principal side effects from the drug itself, though, affect the brain and are called amyloid related imaging abnormalities (ARIA). This can include brain edema or swelling (ARIA-E) and brain bleeding or hemorrhage events (ARIA-H).
ARIA-E, which occurs in about 13% of treated patients, is asymptomatic in most patients, discovered only on an MRI scan. But it is associated with symptoms in about 3% of treated patients and can include headaches, mental or visual changes, weakness and seizures. These symptoms usually do not require hospitalization or treatments, and do resolve over two to four months, but in a very small number of cases, ARIA-E and ARIA-H have been fatal. After an initial MRI to determine eligibility for treatment, three MRI scans are required for safety monitoring during the first seven months of treatment.
The burden of getting intravenous infusions every two weeks is another consideration for patients. Many other drugs are given by infusion, but these are often given less frequently. Infusions may be given in certain medical offices or in hospitals but often are performed in commercial infusion centers. Local access and availability of infusion centers may be problematic in some geographic areas, leaving some patients hard-pressed to access the drug.
The development and approval of Leqembi is a milestone. But there is a need to develop drugs with greater effectiveness, and that can be given to more people with AD at a lower cost and with a lower patient burden. Now that it has been shown that this disease is not intractable to treatment, development of other drugs of greater efficacy, perhaps targeting other aspects of the disease biology, should proceed apace.
While reversal of AD symptoms still seems a very distant possibility, the current advances make us see that possibility on a closer horizon — one where progressive deterioration from Alzheimer’s disease might be alleviated.