Alzheimer's R&D suffers as trial failure rate hits an 'astounding' 99.6%

Jeffrey Cummings

Jeffrey Cummings is directing one of the few early-stage studies underway on an Alzheimer's therapy. And now that he's scanned the records of, he's acutely aware of just how small his chosen field is.

"There are 100 trials of about 80 drugs currently in the pipeline," Cummings, director of the Cleveland Clinic Lou Ruvo Center for Brain Health, tells FierceBiotech. Looking at Phase I, Cummings along with Kate Zhong, senior director of clinical R&D, and Touro University medical student Travis Morstorf, found just 30 studies--"which isn't enough to drive robust research in the field."

Late-stage Alzheimer's research has been a disaster zone so far for the big players who have braved the field. Eli Lilly's ($LLY) solanezumab and bapineuzumab at J&J ($JNJ) and Pfizer ($PFE) both failed spectacularly in Phase III tests. And while the companies continue to plug away--Lilly has a new study focused on solanezumab in earlier-stage Alzheimer's patients--the R&D arena has racked up a whopping 99.6% clinical trial failure rate, according to Cummings' review of the trial data from 2002 to 2012.

"That's an astounding failure rate," says Cummings. "It means that none of the disease modifying agents have come to fruition."

Cummings drives home the point that the numbers clearly show that there isn't enough being done about funding new work on Alzheimer's. The NIH spends $600 million a year on Alzheimer's disease, one tenth of the money that goes to cancer drug research. Industry leaders, meanwhile, have been leery about investing in Alzheimer's drug research as well, particularly in light of recent setbacks.

The number of experimental Alzheimer's drugs in the clinic has dropped over the past 5 years, Cummings adds, even as the number of patients with the memory-wasting disease grows by millions. And Cummings is hoping to use these numbers to help prod additional investment in the field.

Cummings own work in the field illustrates the promise of repurposing known drugs, as well as the devilishly difficult nature of the work.

Like many others in the field, Cummings is following the trail of amyloid beta, the toxic protein often found clustered in the brains of patients. In animal studies carried out at Case Western, the cancer drug bexarotene (marketed as Targretin by Eisai, which recently outlicensed the U.S. rights to Valeant ($VRX)) was able to eliminate amyloid beta from the brains of mice modeled for the disease. Notably, the animal studies also demonstrated an improvement in cognition, says Cummings, who's done consulting work for Eisai.

The trouble was that a subsequent attempt to confirm those results on amyloid beta in animals failed. And the chief investigator, Gary Landreth, wondered if the clusters were even to blame for the disease, focusing on soluble forms of the protein and underscoring the general lack of certainty about what causes Alzheimer's to begin with.

All of the preclinical studies of this drug show something different, Cummings agrees, but there is some consistency on cognition. He's now testing the drug in a small group of patients recruited for a Phase IIa imaging study, which will look at the levels of amyloid beta in the brains of Alzheimer's patients following treatment.

Regardless of the outcome, though, Cummings wants to see a whole new slate of drugs and theories being tested in the clinic. And that won't happen unless someone is ready to pay a bigger tab.

"We need more investment at the NIH, that would re-attract biotech and pharma funding," says Cummings, "then we would see some successes."

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