Can Lecanemab Succeed Where Aduhelm Failed?

The announcement of positive phase 3 results for the investigational Alzheimer’s disease drug comes against a backdrop of Aduhelm flaming out. Both drugs are predicated on the theory that Alzheimer’s is caused by beta-amyloid deposits.

After the failure of Aduhelm (aducanumab), Eisai and Biogen are back at it with another drug that is designed to treat Alzheimer’s disease by reducing beta amyloid deposits in the brain.

The two companies issued a joint press release last night announcing positive results for the drug, called lecanemab (development code: BAN2401) from a phase 3, placebo-controlled that included 1,795 participants with mild cognitive impairment due to Alzheimer’s disease or mild Alzheimer’s disease.

The companies announced in July 2022 that the FDA had agreed to put lecanemab on its accelerated approval pathway — the agency’s speedier approval process — and that an approval decision (the so-called PDUFA date) is scheduled for Jan. 6, 2023.

The announcement of the phase 3 trial results was treated as major news and was covered by the Wall Street Journal and the New York Times as well as outlets that cover the biotech industry such as Stat and Endpoints News.

“In the first look at phase 3 data for lecanemab, Eisai and Biogen’s follow-up Alzheimer’s drug to the embattled Aduhelm launch, results show the drug passed with flying colors on a test looking at memory, problem solving and other dementia metrics” was the lede on the Endpoints News story.

And here is the second paragraph of Stat’s story: “The positive result is welcome news for the millions of people living with Alzheimer’s and a big win for Eisai and Biogen, giving the companies a potential blockbuster product…”

According to last night’s press release, lecanemab met the primary endpoint of reducing cognitive and functional declined as measured by a test the Clinical Dementia Rating-Sum of Boxes (CDR-SB). More specifically, the treatment reduced decline by 27% compared to those in the placebo group, the press release said.

As with Aduhelm, brain swelling and small bleeds are side effects of lecanemab. The press release says that 21.3% of the people in the lecanemab group had swelling or bleeds compared with 9.3% in the placebo. However, the proportion of patients who had symptoms from swelling and bleeds was far less (2.3% in the lecanemab group had symptoms from brain swelling and 0.7% had symptoms from brain bleeds).

The press release said Eisai researchers will present the results from the phase 3 trial, which is called Clarity AD, at the Clinical Trials of Alzheimer’s Disease Congress meeting in San Francisco on Nov.29, 2022, and also publish them in a peer-reviewed journal (the journal was not named in the press release).

Lecanemab and Aduhelm are both designed to reduce beta-amyloid plaques in the brain and, as such, are predicated on theory that those plaques have a causative role in Alzheimer’s disease. The press release about lecanemab quotes Haruo Naito, the CEO of Eisai, as saying the positive results for lecanemab “prove the amyloid hypothesis.”

Eisai and Biogen teamed up on Aduhelm, but the problematic drug was strongly associated with Biogen. Yesterday’s press release says that Eisai will be leading the development and regulatory submissions process for lecanemab.

Eisai’s ($ESLAY) stock price shot up by more than 60% today and was trading at $63.61 this afternoon. Biogen’s ($BIIB) stock price was up by almost 40% and was trading at $274.70 this afternoon.

The positive news and spin about lecanemab yesterday and today stand in stark contrast to the controversy that engulfed Aduhelm.

When the FDA approved the Aduhelm on June 7, 2021, three members of the outside advisory committee that had recommended that it not be approved resigned in protest. One of the resigning members called the FDA’s OK of Aduhelm “probably the worst drug approval decision in recent U.S. history.” The clinical trial results for Aduhelm were ambiguous with one trial showing a positive result (as measured by scores on the CDR-SB) and the other, not. Press reports said the agency’s approval of Aduhelm was one of the reasons that interim commissioner, Janet Woodcock, did not get the job on a permanent basis.

The pricing of Aduhelm also created headwinds for the drug and Biogen. It was originally priced so a year of treatment would cost $56,000. The Alzheimer’s Association and other groups objected. Biogen later slashed the price in half.

Then in April 2022, CMS announced that it would restrict coverage of Aduhlem to people enrolled in clinical trials. In June, Biogen pulled the plug on what was to be a large real-world evidence of Aduhelm called ICARE-AD. The statement on the clinicaltrials.gov website says that “as a result of the national policy for coverage, it is expected there will be limited aducanumab-avwa prescription and usage in routine clinical practice making the study not feasible for enrollment.”