BioPharma, Pharma

Late-stage Alzheimer’s failure ripples through the industry

Eli Lilly announced Wednesday that its late-stage trial of solanezumab did not slow progression of Alzheimer's disease in patients with mild symptoms, triggering a number of biotech shares to fall.

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In a major blow for Eli Lilly and the Alzheimer’s community, the company announced Wednesday that top-line results from its Phase 3 trial of solanezumab did not show a reduction or slowing in cognitive decline.

The trial, dubbed Expedition 3, represents a long journey and hundreds of millions of dollars spent in pursuit of the first-ever treatment for the neurodegenerative disease, which affects more than 5 million Americans.

In a company new release, Eli Lilly chairman, president, and CEO John Lechleiter said its Alzheimer’s program will now be reassessed.

“The results of the solanezumab EXPEDITION3 trial were not what we had hoped for and we are disappointed for the millions of people waiting for a potential disease-modifying treatment for Alzheimer’s disease,” Lechleiter said. “We will evaluate the impact of these results on the development plans for solanezumab and our other Alzheimer’s pipeline assets.”

Along with the drug candidate, a number of prominent research theories were on trial. Chief among them was the theory that Alzheimer’s is caused by  or at least associated with  a build-up of beta-amyloid in the brain.

Lilly’s solanezumab sought to slow disease progression by targeting beta-amyloid circulating in the bloodstream. It was hoped this would minimize plaque build-up in the brain and interfere with the course of the disease.

Unfortunately, no meaningful change was observed in the 2100-person randomized, double-blinded trial. Eli Lilly shares subsequently dropped 14 percent in premarket trading. According to the news release, the company expects to write-off $150 million in the fourth quarter alone.

The fallout also hit Biogen stocks, which fell 8 percent in premarket trading. Biogen is guiding its own beta-amyloid therapy, aducanumab, through two global Phase 3 trials. The company secured an FDA fast track designation in September.

Merck was not spared either. The pharma giant has a late-stage Alzheimer’s candidate verubecestat (MK-8931) in its pipeline, which hinges on the amyloid hypothesis. Its shares dropped 3 percent in a busy premarket trading session.

Yet another company, Prothena, witnessed its shares fall 10 percent, based on its scientific focus on the role of amyloid. The hit comes despite the fact that the company isn’t directly targeting Alzheimer’s disease.

At least one company has come out on top. Anavex shares rose 4 percent this morning, based on its lead candidate Anavex 2-73. That compound targets Alzheimer’s through a distinct pathway that does not involve beta-amyloid.

Expedition 3 was not the first late-stage trial performed on solanezumab. In 2012, Lilly delivered top-line results on two Phase 3 trials that showed the drug did not meet its primary endpoints. However, a breakdown of the trial results gave hope that it may be effective for patients with early, mild symptoms of the disease.

Expedition 3 gave new hope to patients but ultimately, did not show efficacy.

In a statement released today, the Alzheimer’s Association urged the research community to continue its search for disease-modifying therapies.

On behalf of the millions of people living with Alzheimer’s disease and their families that we serve and represent, the Alzheimer’s Association is disappointed with the negative results of this clinical trial.

We sincerely hope that the ongoing Alzheimer’s prevention trials (A4 Study, Alzheimer’s Prevention Initiative, DIAN-TU) that are testing solanezumab and other anti-amyloid agents will continue. These other programs have different ways of acting on the amyloid pathway and some are also addressing the disease at a much earlier stage when these drugs may still prove to be effective.

Eli Lilly will report more detailed results from the trial on Thursday, December 8 at the Clinical Trials on Alzheimer’s Disease meeting.

Photo: Ian Waldie, Getty Images

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