Eisai made history last year as Biogen’s partner on Aduhelm, the first approved Alzheimer’s treatment in decades. And yes, they know the launch could have gone better.
“Lessons learned? Yes, there were many. We can go on hours about things that we could have done better,” said Ivan Cheung, Eisai’s chairman and global president of the neurology business group. “But that's what it is to be the first.”
Now Eisai will have a chance to be second, too, or at least race Eli Lilly for the honor. The Japanese pharma and Biogen are moving their follow-up treatment, lecanemab, through the rolling submission process, hoping to obtain an accelerated approval just like the predecessor therapy did.
And this time, Eisai is in the driver’s seat. While Biogen took the lead on Aduhelm's clinical development, regulatory interactions with the FDA and commercial rollout, the script has flipped for lecanemab.
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Cheung knows his team is heading into challenging terrain with lecanemab, but this is a place Eisai has been before. In 1996, the company launched Aricept, a daily oral treatment for Alzheimer’s, jointly marketed with Pfizer, that was groundbreaking at the time.
When Aricept launched, Alzheimer’s was not very well understood by the general public. Some even questioned whether it was a disease to be treated or just a part of the natural aging process, Cheung said.
Aricept, which is known generically as donepezil, treats symptoms of dementia caused by Alzheimer’s and was eventually approved for all stages of the disease in 2006. But the therapy’s effects are temporary, only lasting as long as the patient takes it. Symptoms are managed while taking Aricept, but the treatment does not affect the underlying cause of disease. That’s what Biogen and Eisai are trying to do with Aduhelm, and soon, lecanemab.
“It was extremely difficult in the beginning days of Aricept, and you can ask me whether the beginning of Aduhelm was more difficult than that of Aricept, I don't know how to compare,” Cheung said. “But we have experiences to tell you it's never easy to be the first, and we knew that.”
Lecanemab is not being set up as a “me too” treatment behind Aduhelm. Cheung has big hopes that the up-and-coming treatment will take over the market just as Aricept did two decades ago.
One thing lecanemab can potentially improve upon is Aduhelm's rate of amyloid-related imaging abnormalities (ARIA), a problem that shows up in MRI imaging that suggests swelling or bleeding in the brain. This is a known side effect associated with amyloid therapies that has cropped up in Aduhelm trials. In November 2021, one trial patient taking Aduhelm reportedly died after an ARIA diagnosis.
With Aduhelm, a pooled analysis of two phase 3 studies found MRI abnormalities in 41% of patients, compared to just 10% of placebo patients. The adverse event was asymptomatic in 76% of cases, and only 0.3% were reported as serious.
Michael Irizarry, M.D., Eisai’s senior VP of clinical research and deputy chief clinical officer of the neurology business group, said that a midstage study of lecanemab showed about a 10% incidence of ARIA, with only 2% reported as symptomatic. With the lessons learned from Aduhelm, Eisai has a monitoring plan in place for any patient identified to have ARIA.
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Another way lecanemab is setting itself apart from its predecessor is that the phase 3 clinical trial, called Clarity AD, is geared toward discovering the therapy's clinical benefits. Remember, Aduhelm was controversially approved on the basis of biomarker data—the new Alzheimer’s buzzword—which means the therapy showed it reduced beta amyloid in the brain. Researchers believe beta amyloid builds up in the brain of Alzheimer's patients, causing problems.
The FDA green light was not based on evidence that Aduhelm is clinically beneficial and mitigates cognitive decline. For that, Biogen and Eisai are working on a phase 4 confirmatory trial to prove clinical benefit and maintain the FDA approval.
This time around with lecanemab, Eisai is shooting to have those data in hand much sooner in the product's life span. The phase 3 trial completed enrollment in March and will try to verify earlier findings that the therapy can reduce amyloid in the brain and therefore have an impact on clinical benefit and that amyloid biomarker.
Earlier studies of lecanemab have shown consistent reduction of amyloid and improvements in clinical decline, Cheung said. These data were published in a peer-reviewed journal.
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“We as a team are confident in that clinical efficacy from that phase 2b data, but of course, that’s only one study. That’s why we’re doing Clarity AD to prove it one more time,” Cheung said.
The Clarity study, which is expected to read out in the fall, will be much bigger than the midstage test and is being done with “rigor” in terms of recruitment and how it’s conducted, Irizarry added.
Eisai also said Wednesday that enrollment has begun in the phase 2/3 Tau NexGen study being conducted by the Washington University School of Medicine in St. Louis, which will use two of the Japanese pharma's Alzheimer's therapies. Lecanemab will serve as the background anti-amyloid therapy, while an earlier-stage asset, tau antibody E2814, will be the investigational medicine. The study features asymptomatic and symptomatic patients with dominantly inherited Alzheimer’s, a type of the disease that is caused by genetic mutations and is passed down in families.
Calling back to the Aricept days, Cheung said another thing that’s different this time around is that Alzheimer's patients are identified earlier in the disease course. So new Alzheimer’s treatments can be offered earlier in a patient’s journey to prevent damage that can’t be corrected later.
Explaining the difference between a biomarker and clinical efficacy remains a communication challenge for patients, though. Not to mention the fact that treatments like Aduhelm or lecanemab are meant to address the disease, not necessarily reverse symptoms.
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“What it means to receive a so-called disease-modifying therapy versus receiving a symptomatic treatment, I think the majority of the public don't understand that,” Cheung said. “This is about early diagnosis, early treatment, and then you can slow down the progression of the disease. It’s a fairly different concept.”
To help with the public understanding of lecanemab, Eisai is laying all the data out for the world to see.
“We don't believe in any easy path. I think Alzheimer's is challenging, but we are confident and at the end of the day the data speaks for itself,” Cheung said.