Roche brings an Alzheimer's drug back from the brink with another PhIII endeavor

Roche ($RHHBY) is resuscitating development for gantenerumab, an Alzheimer's treatment that flamed out in Phase III late last year, as recent clinical results have emboldened the company to launch new studies.

Gantenerumab is an antibody designed to rid the brain of a protein called beta amyloid, which forms toxic plaques that many researchers believe are at the root of Alzheimer's memory-destroying effects. That hypothesis--like most things in Alzheimer's--has a dismal record in the clinic, however, as similar treatments from Eli Lilly ($LLY), Johnson & Johnson ($JNJ) and others have failed in Phase III trials.

But Roche believes it has learned the lessons of amyloid's past failures, and the company is now "developing novel approaches to implement higher doses" in new Phase III trials, a spokesman said. Roche said it has requested feedback from global regulators on its plans for new studies, but the company isn't disclosing details on timing or trial design.

This may sound familiar. The initial excitement around gantenerumab was tied to similar optimism that Roche had adapted its approach to avoid the pratfalls of antibodies past. Solanezumab and bapineuzumab, two Phase III flops, enrolled patients in various stages of Alzheimer's, which the companies later said was a misstep. Roche, by contrast, focused on presymptomatic patients, believing that targeting Alzheimer's early in its spread would lead to better outcomes. But, like its predecessors, gantenerumab failed to significantly improve cognition and function compared to placebo, and Roche discontinued the trial, called Scarlet Road, in December.

The VU University Medical Center's Philip Scheltens, who participated in the failed gantenerumab study, was at the Alzheimer's Association International Conference (AAIC) on Wednesday to explain the company's move, citing evidence that that dose used in the trial was simply too low to gain an effect. Researchers will have to titrate higher in the next study to gain the expected response, he told a gathering of reporters, adding that evidence of ARIA-E (brain swelling) would be a sign that the antibody was working.

Roche hinted at a re-evaluation of gantenerumab's potential earlier this year, after Biogen ($BIIB) made a splash with early but positive results with an amyloid antibody of its own. That gave Roche "renewed confidence" in the amyloid hypothesis, COO Daniel O'Day said in April. The company is also moving into Phase III with the amyloid-targeting crenezumab, licensed from AC Immune, despite mixed results from a mid-stage study disclosed last year.

Meanwhile, gantenerumab is in the midst of a second, ongoing Phase III studied called Marguerite Road, which began in May 2014. In that study, the company is targeting patients with mild Alzheimer's-related dementia and testing whether gantenerumab can better forestall the worsening of symptoms than placebo over 24 months.

John Carroll contributed to this report.

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