Jointly developed by Eisai Co. and Biogen Inc., lecanemab is a laboratory-made antibody designed to target a form of amyloid called protofibrils, which were implicated in the case of a Swedish family ravaged by early-onset Alzheimer’s. In an 18-month efficacy trial involving 1,800 patients with early Alzheimer’s, those who received lecanemab, which will be sold under the brand name Leqembi, saw a significant reduction in brain amyloid levels. More importantly, the drug slowed their cognitive and functional decline by 27% compared to a group that received a placebo.
2. What is lecanemab’s availability?
Based on the drug’s amyloid lowering ability, the FDA gave a greenlight for it using an accelerated approval process for drugs that treat serious conditions, fill an unmet need and perform in a way that predicts a benefit to patients without actually measuring that benefit. Full FDA approval isn’t likely to come before later this year. The US federal Medicare program for the elderly, which covers most people with Alzheimer’s, has indicated it won’t broadly cover amyloid-lowering drugs until they receive full approval based on clinical benefits, as opposed to accelerated approval based on amyloid lowering alone.
3. Who is lecanemab for?
The drug has been tested on people in the early stages of the disease, in which symptoms include mild forgetfulness that often accompanies aging but also possibly problems concentrating. Most patients in the big lecanemab trial had mild cognitive impairment, while some had mild dementia. To qualify for the drug, people will likely need to be tested for signs of brain amyloid, present in more than two-thirds of Alzheimer’s patients and around half of 10 million more with mild cognitive impairment. A brain amyloid PET scan is one possibility but it can cost as much as $7,000. Medicare has restricted coverage of the scans, and most hospitals perform this test only occasionally. Spinal taps are another way to get tested, but they’re invasive and sometimes painful, so some patients shy away. A few blood tests available commercially in the US can provide an indication whether amyloid is present in the brain, but none are routinely covered by insurers or cleared by the FDA. Japan’s health ministry approved such a test, developed by Sysmex Corp and Eisai, in December.
4. What are the limitations of lecanemab?
The slowing of cognitive decline seen in the trial was modest, and the drug does not stop disease progression. Lecanemab’s benefits come with side effects. In the trial, more than one in five people on the medicine experienced brain swelling or bleeding. Most cases weren’t symptomatic, though patients sometimes had headaches, visual disturbances and confusion, and five people developed large brain hemorrhages. Two people taking blood thinners died in the extension phase of the trial; Eisai says lecanemab wasn’t to blame. The drug is administered as an infusion every two weeks, which means patients must receive it at a health center. It’s likely to be expensive. Using earlier stage studies, Eisai researchers estimated the annual price might range from $9,000 to $35,000.
5. Why was the approval of a different amyloid drug controversial?
In June 2021, the FDA approved Aduhelm, another Alzheimer’s treatment from Biogen and Eisai, despite conflicting trial results. One big study showed no effect while another showed a small benefit in slowing cognitive decline; both trials were stopped early by Biogen, making the results hard to interpret. The agency cleared the drug against the advice of a panel of outside medical experts. Three members of the group resigned afterward, and Medicare heavily restricted payments for Aduhelm. The drug’s makers eventually stopped marketing it in the US. Congressional investigators in December concluded that the Aduhelm approval process was “rife with irregularities,” stating that the FDA collaborated excessively with Biogen while assessing the drug.
6. Will lecanemab have competitors?
Not many initially. The main potential competitor nearing approval is Eli Lilly & Co.’s donanemab. In a phase 2 trial reported in 2021, donanemab dramatically lowered brain amyloid and slowed cognitive and functional decline by 32% in people with early stage Alzheimer’s. The company has applied for accelerated approval in the US based on amyloid lowering. It is conducting a larger phase 3 trial that should report results this year; a positive outcome could lead to full approval. Another amyloid lowering antibody from Roche Holding AG called gantenerumab failed to slow cognitive decline in two large trials reported at a medical conference in November.
7. What are the future paths for Alzheimer’s research?
After the Aduhelm debacle, the lecanemab results strengthened the argument that researchers are on the right path in targeting amyloid. Still, it’s not yet clear why the lecanemab results were better than those from most amyloid-lowering medications. Some researchers suspect that a certain threshold of amyloid removal must be met before drugs show a benefit. But with the benefits limited even to those in the early stages of Alzheimer’s – possibly because damage to key brain areas is already extensive – some researchers are focused on getting ahead of the disease. Brain scan studies suggest that amyloid starts accumulating in the brain as long as two decades before someone has dementia. In massive final-stage trials underway at Eli Lilly Co. and Eisai Co., researchers plan to test amyloid-removing drugs on thousands of healthy adults. The hope is to stave off cognitive decline before it begins, or at least delay it. Meanwhile, researchers are also focused on other things that go awry in Alzheimer’s, including an increase in a second protein called tau, and brain inflammation that may lead to nerve cell death. Various companies are targeting both these processes with other drugs in testing, though there have been no breakthroughs so far.
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