Why Genentech's betting on an approach to treating Alzheimer's when rivals have failed

AP/Alastair Grant

• Genentech, part of pharma giant Roche, has been developing a pipeline of neuroscience drugs at a time when other pharmaceutical companies have largely left the space.
• Among those drugs are two treatments for Alzheimer's disease, a condition that hasn't had a new treatment for 15 years and has faced a number of setbacks over the past few years.
• Paulo Fontoura, global head of neuroscience at Roche, is optimistic about the company's approach, despite the setbacks. "Even though we haven't really had all that much success, i think in my mind the jury's still out and there's still hope," he said.

The search for new Alzheimer's disease may have hit some setbacks, but companies are still optimistic about finding new treatments.

Alzheimer's affects more than 5 million Americans, a number that's expected to balloon to 13.8 million by 2050. There are only four drugs that have been approved to treat the symptoms of the disease, and the most recent drug approval happened in 2003.

One approach companies are trying is to target certain beta amyloid proteins, which accumulate in the brain of people who have Alzheimer's. This idea of targeting beta amyloid deposits in the brain to clear them out is known as the "amyloid hypothesis."

But there's one major drawback to the amyloid-beta approach: In people who have Alzheimer's, these deposits build up in certain parts of the brain, but it's still not known whether the plaques cause the disease, or if they're just a byproduct. What does seem to be well established is that in people with the genetic version of the disease, there is a strong relationship between those mutations and amyloid plaques.

Genentech is one of the companies developing drugs that go after the amyloid hypothesis. The company, a member of the Roche Group, has two Alzheimer's drugs in late-stage development.

• In February 2017, Genentech and its partner AC Immune launched a phase 3 trial for crenezumab, a drug that's targeting amyloid deposits in the brain. It's expected to have data in 2020.
• The other is gantenerumab, a drug also targeting amyloid that failed earlier trials. The hope is that by increasing the dose, it might work. Genentech started a new phase 3 trial for gantenerumab in 2017.

Paulo Fontoura, global head of neuroscience at Roche told Business Insider that the two treatments target different species of amyloid proteins. That could make it possible to be used in combination.

The amyloid hypothesis has already been put to the test and seen a few failures. For one, Merck's now-failed BACE inhibitor was also acting on the amyloid hypothesis to prevent the protein from forming and keep the disease from progressing. Solanezumab, a drug developed by Eli Lilly that also acts on the amyloid hypothesis, failed some key clinical trials, though the company is still testing it in the pre-clinical stages of the disease.

Fontoura said the failed trials have been helpful for its ongoing work. For one, it's made it clear that using tools like PET scans and cerebrospinal fluid testing can help pinpoint which patients have amyloid present in the brain for the treatments to act on. In turn, it's helping researchers treat patients in trials earlier since they can be identified by the amyloid in their brains. The advances have him hopeful.

"Even though we haven't really had all that much success, I think in my mind the jury's still out and there's still hope," Fontoura said.

Beyond Alzheimer's, Genentech is working on other neuroscience programs in multiple sclerosis and rare neurologic conditions like Huntington's and spinal muscular atrophy, at a time when other pharmaceutical companies have largely left the space. For example, Pfizer said in January that it will be cutting 300 jobs as part of its closing of its neuroscience research and development program, and it was a brutal 2017 for Alzheimer's research as a number of key trials failed.

Fontoura attributed the push to keep developing treatments in part to the scientific developments that have helped demystify what causes certain neurologic conditions.

"I do think the science is becoming mature enough that we are starting to understand really at a molecular level how a lot of these diseases are caused," Fontoura said.