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BACEless: Eisai, Biogen Pull Plug on Alzheimer’s Drug in Final Stage

Xconomy New York — 

Add another once-promising Alzheimer’s disease drug to the scrap heap.

Eisai and Biogen (NASDAQ: BIIB) are halting a Phase 3 test after an independent safety review concluded the risks of experimental Alzheimer’s drug elenbecestat outweigh the benefits. The companies did not explain what the independent board found. Some drugs that work the same way have failed because of safety problems, while others have failed to boost cognition sufficiently. The companies said detailed data would be presented at a future medical meeting.

Elenbecestat is known as a BACE inhibitor, a type of drug that blocks the enzyme beta secretase 1 (BACE1), which helps turn the protein amyloid beta into sticky plaques in the brains of Alzheimer’s patients.

Many of the experimental Alzheimer’s drugs that have failed—as of 2014 the failure rate was 99 percent, and it’s only grown worse since then—were tested in patients who were clearly showing symptoms. Experts in the field now agree that preventing amyloid plaques or breaking them up in these patients is too late, akin to adding a bandage to a person bleeding to death.

There was some hope that tackling amyloid in patients with milder symptoms might help. Eisai and Biogen were testing elenbecestat in two placebo-controlled studies, totalling 2,100 patients who had mild cognitive impairment or early Alzheimer’s with confirmed signs of amyloid in the brain. The main goal was to show a change in score on a scale used to measure the severity of dementia symptoms. But as Biogen demonstrated earlier this year with its failed drug aducanumab, tackling amyloid beta even at an earlier stage of the disease has not worked, either.

There is a pressing need to blunt the impact of Alzheimer’s disease. In the US alone, more than 5 million people are afflicted, most of them over age 65, and the cost of care will reach $290 billion this year, according to the Alzheimer’s Association. It’s the sixth-leading cause of death and will keep rising as the population ages. The failure of amyloid-focused drugs has amplified calls for other types of research and heightened resentment about the decades-long obsession with amyloid.

Like nearly every other type of Alzheimer’s drug, BACE inhibitors have not fared well. In 2017, Merck (NYSE: MRK) stopped work on its pill verubecestat after an independent board concluded the drug would not help patients. Novartis (NYSE: NVS) and Amgen (NASDAQ: AMGN) halted its umibecestat program in July after a planned interim review found worsening cognitive function in patients treated with the drug.

Japan-based Eisai, which has its US headquarters in Woodcliff Lake, NJ, has been working with Cambridge, MA-based Biogen on Alzheimer’s drug research since 2014. The companies said Friday that ending work on elenbecestat does not affect their other Alzheimer’s program, an amyloid-busting drug called BAN2401, which is in Phase 3 studies.

In a Friday research note, SVB Leerink analyst Geoffrey Porges wrote that elenbecestat’s failure was widely expected in the investment community following aducanumab’s failure earlier this year. He added that stopping the elenbecestat program is another step in “the unwinding of Biogen’s expensive, painful, and ultimately fruitless investment in Alzheimer’s disease drug development.

“While there may have been similar failures in other companies, and possibly even more costly investments that failed, as a percentage of one large company’s value, and its total R&D investment, it would be harder to find a bigger disappointment,” Porges wrote.

When Biogen and Eisai inked their partnership in 2014, aducanumab was in early-stage testing and Biogen’s stock price was around $332. Midday Friday, shares of Biogen traded at $236.56—up 1.86 percent. Porges wrote that the end of the elenbecestat program is a relief to Biogen investors, as the company moves away from beta amyloid drug research. But Biogen still needs to settle its financial obligations to Eisai, and end its funding for BAN2401. Those steps will take several more years, Porges wrote.

Photo by Flickr user Amit Patel via a Creative Commons license