Contrarian thinking

Why Genentech, Roche say neuroscience R&D is ripe for investment

While many pharma companies are exiting or externalizing neurology R&D, a few have decided to double down, seeing the glimmer of a new understanding of CNS diseases where others see biological black boxes leading to late-stage clinical failures.

Among these contrarians, Roche and its Genentech Inc. unit say neuroscience is breaking open because of advances in genetics, imaging and an improved understanding of pathways and targets.

Based on the foundation provided by those advances, the pair is investing in internal R&D and deals to build a pipeline of potentially disease-modifying treatments for neurodegenerative diseases, pain and psychiatric indications.

"What we do is focus on mechanism in choosing what to work on - what we understand and now can make tractable," said Luca Santarelli, head of neuroscience research in Roche's Pharma Research & Early Development (pRED) group.

Roche and Genentech also say they are learning from first-generation failures to design better molecules against known targets such as beta amyloid in Alzheimer's disease.

"In Alzheimer's, I think we have learned a lot about the disease mechanism and are now learning about the course - it's as long as 20 years, which we did not think [was the case] before," said Santarelli.

These changes are leading the companies to new patient populations and clinical trial designs.

Sean Bohen, SVP of early development at Genentech, said this approach required challenging the conventional wisdom for how to test its candidates.

According to Bohen, the company asked itself whether a classical development plan in patients diagnosed with dementia could lead to a negative result, but not because the target was wrong.

"What about treating people who are cognitively normal - redefine the patient population, test the therapeutic and test new endpoints?" he said. "That's what we're doing."

Roche and Genentech, which have separate R&D organizations for discovery through Phase II development, each have an antibody against beta amyloid in clinical trials for AD.

Roche is testing gantenerumab in a Phase II/III trial in patients with prodromal AD, who have memory loss but do not yet have dementia.

Genentech is testing crenezumab to prevent AD in cognitively normal patients with a mutation that causes early onset AD, and in two Phase II trials to treat mild to moderate AD.

While the groups are taking

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