Most ‘blockbuster’ treatments for diseases like Alzheimer’s fail, but here’s why researchers aren’t giving up hope

While treatments for diseases like cancer have had an innovation gold rush, neurological diseases haven’t seen the same kind of development.

In November, the field faced another setback after an Alzheimer’s disease drug failed a critical late-stage trial. But other drugmakers seem to still have hope, even if the odds are stacked against them.

At the Forbes Healthcare Summit on Thursday, two CEOs from companies in the neurodegenerative space spoke with Susan Schneider Williams, whose husband Robin Williams was diagnosed with Lewy Body Dementia (LBD) after his death in 2014. The condition is the second most common form of dementia, next to Alzheimer’s.

Only four approved drugs are in use to treat Alzheimer’s; on average about 99% of all drugs in clinical trials never actually make it to approval. There are no approved treatments for Lewy Body disease.

Axovant is developing drugs for Alzheimer’s and LBD, while Denali Therapeutics is exploring treatments for Alzheimer’s and ALS.

Speaking with Denali Therapeutics CEO Ryan Watts and Axovant CEO Vivek Ramaswamy, Schneider Williams expressed frustration about not knowing the kind of dementia her husband had.

“It wasn’t until three months after Robin left that I found out the name of what took him,” she said. Based on his symptoms, Williams had previously been diagnosed with Parkinson’s, a neurodegenerative disease characterized by problems with movement, but it wasn’t until later that a doctor diagnosed him with LBD after discovering the presence of Lewy bodies in his brain.

Combining drugs

Both Ramaswamy and Watts expressed interest in combining different therapies to treat complex conditions such as LBD.

“We can just give up,” Watts, who admitted initially being himself hesitant about combinations in neurodegenerative diseases, said. “But that’s not what we should do. We should try these other novel approaches.”

Ramaswamy said people working in the neurodegenerative space should take a similar approach to the one that cancer researchers have taken over the past decade. “The drugs all come step-by-step, without a single silver bullet,” said Ramaswamy.

Axovant’s Alzheimer’s compound, RVT-101, is being tested in combination with Aricept, an available widely-used drug that is used to treat Alzheimer’s symptoms including memory loss and confusion. Together, the two drugs appeared to slow people’s loss of cognition and improve their ability to perform daily tasks – and these results were better than when Aricept was taken alone. The company’s phase 2b trial was promising, and it launched its phase 3 trial in October 2015. Data from that trial should be coming out in 2017.

Two of the main targets Alzheimer’s drugs have been going after are called tau and amyloid (solanezumab, the most recent drug to fail a phase 3 trial, was going after the amyloid deposits in the brain to clear them out and treat the disease). Drugs going after both targets have had setbacks in the last year. Axovant’s compound goes after a different mechanism, a receptor in the brain called 5-HT6, though drugs going after this receptor have also had setbacks.

So the best way to turn things around? Take it slow and get more drugs approved, even if they may only help incrementally.

“This, more than any other, needs to turn cycle of failure into success,” Ramaswamy said. “All it will take is a single success to be a catalyst for change.”