Another blow to Alzheimer’s field as two drugs fail in study of early-onset disease

Lilly and Roche said that the Phase II/III DIAN-TU trial of their amyloid beta-targeting drugs – gantenerumab and solanezumab – failed to meet its primary endpoint in patients genetically predisposed to early-onset Alzheimer’s disease.

Dementia or brain damage and injury as a mental health and neurology medical symbol with a thinking human organ made of crumpled paper torn in pieces as a creative concept for alzheimer disease.

The Alzheimer’s disease field suffered a major letdown Monday as two drugs being tested in a large academic clinical trial failed.

Basel, Switzerland-based Roche and Indianapolis-based Eli Lilly said Monday that both of their respective drugs – gantenerumab and solanezumab – had failed to improve cognition in the Phase II/III DIAN-TU trial, run by Washington University in St. Louis. The 490-patient study, whose name stands for Dominantly Inherited Alzheimer Network Trial, was designed to prevent dementia in patients who had or were at risk for early-onset Alzheimer’s disease caused by a genetic mutation. That particular form of Alzheimer’s, known as autosomal-dominant Alzheimer’s disease (ADAD), accounts for less than 1% of all cases of the disease.

Lilly’s shares fell 3.4% on the New York Stock Exchange when markets opened Monday following the news. Roche’s shares appeared unaffected.

Both drugs are designed to target amyloid beta, the plaques that are known to build up in the brain of Alzheimer’s patients and whose removal has long dominated as a theoretical means to treat the disease.

“Although DIAN-TU did not reach its primary endpoint, the trial represents the first of its kind and a bold undertaking by all partners involved,” Roche Chief Medical Officer Levi Garraway said in a statement. “Given its experimental nature, we are unable to draw firm conclusions about the impact of gantenerumab in autosomal-dominant Alzheimer’s disease.”

Garraway added that the news does not dampen Roche’s confidence in the Phase III GRADUATE studies of gantenerumab.

Still, the trial’s failure won’t help the amyloid-beta hypothesis. Another prominent failure came last year, when Biogen halted its Phase III trials of aducanumab for futility before reviving the drug when a subsequent analysis indicated it had efficacy. Biogen has said it plans to submit aducanumab for Food and Drug Administration approval. Nevertheless, some saw the DIAN-TU study’s failure as having negative implications for that drug as well.

In a note to investors, Baird analyst Brian Skorney pointed out that despite addressing three of the problems that had been pointed out as potential culprits in previous amyloid beta studies – enrolling a genetically homogenous population, giving them large doses of drug and including long follow-up periods – DIAN-TU still failed.

Skorney, a skeptic of Biogen’s aducanumab efforts, said the results also could have a negative read through to the Food and Drug Administration’s review of that drug. On the hand, he wrote, those with a bullish view on aducanumab argue that the FDA would review the drug on its own merits rather than judging it against the failures of other drugs in the amyloid beta class. Still, he argued that people had made similar arguments about Sarepta Therapeutics’ Exondys 51 (eteplirsen) in 2013, and that the FDA had said at the time that a filing for approval would be premature given the failure of other drugs in Duchenne muscular dystropy. Nevertheless, the FDA ultimately approved Exondys 51 in 2016, though the approval was not without controversy.

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