Roche is at an Alzheimer's crossroads after mixed data for AC Immune's drug

Image removed.AC Immune CEO Andrea Pfeifer

An Alzheimer's treatment from AC Immune and Genentech posted mixed results in a midstage study, missing its coprimary endpoints but performing well in patients with milder symptoms. That leaves Roche ($RHHBY), Genentech's parent company, with a big decision to make on whether to take the plunge into Phase III.

The first study, on 431 patients with mild to moderate Alzheimer's, was designed to test crenezumab's ability to slow the decline of cognitive and global function over 18 months. The drug failed to meet statistical significance on both measures for the whole treatment group, AC Immune disclosed, but showed hope for patients with milder disease according to their Mini-Mental State Examination scores.

In the milder group, crenezumab led to a 35.4% reduction in cognitive decline and cut global functional decline by 19.6%, both good enough for statistical significance. Partial results from a smaller biomarkers study showed similar signals: 52% for cognitive decline and 41.5% for global function.

That's all encouraging for AC Immune, CEO Andrea Pfeifer said. Crenezumab's effects were dose-dependent and consistent over time, she said. And, unlike other antibodies targeting Alzheimer's, the drug hasn't run into dose-limiting side effects, meaning it could potentially be administered at higher volumes to boost efficacy.

Crenezumab is a monoclonal antibody that works by clearing buildups of amyloid β from the brain, disposing of a protein believed by many to play a role in the development of Alzheimer's disease. The amyloid β field is haunted by the high-profile failures of antibodies from Eli Lilly ($LLY) and the team of Johnson & Johnson ($JNJ) and Pfizer ($PFE), both of which failed in late-stage trials in 2012. Unlike AC Immune, Lilly decided to go without a Phase II efficacy study for its solanezumab, and J&J and Pfizer ran into serious side effects that limited dosing of their bapineuzumab.

But whether crenezumab even gets a chance in Phase III is up to Roche, and the pharma giant will likely wait to make a final decision on the treatment until full data from the above-mentioned biomarkers study come out in November. That trial is looking to establish a correlation between rate of cognitive decline and amyloid β reduction.

According to Bernstein analyst Tim Anderson, drug companies don't normally advance a compound into Phase III unless they estimate the probability of success at more than 60%. For Alzheimer's, that threshold dips below 25%, he said, due both to the vexing uncertainty around the disease and the colossal commercial opportunity presented. A drug that could successfully modify the progression of Alzheimer's could make Lipitor, which peaked at around $12 billion a year, "look like a mid-sized product," Anderson wrote in a note to investors.

In the meantime, AC Immune believes its Phase II data are cause for hope in the long-troubled field of drug development. Given further study, crenezumab has the potential to show significant effects in a brain-destroying disease that afflicts 44 million people around the world, Pfeifer said.

"This trial definitely shows that A-beta is not dead, and if you have a good safety profile, you will be able to improve the progression of Alzheimer's," Pfeifer told FierceBiotech.

Beyond the Phase II studies, Roche and AC Immune are collaborating with the National Institutes of Health to test crenezumab in 100 patients who have yet to show signs of Alzheimer's but carry a genetic profile that predisposes them to the disease.

- read the statement