Roche Holding AG’s experimental drug crenezumab failed to improve thinking and memory in people with Alzheimer’s disease, though study results leave open the possibility that it might help those who don’t show symptoms.
The medicine didn’t slow a decline in cognitive ability for mild to moderate Alzheimer’s disease in either of two mid-stage trials, and it didn’t help patients function better, the Basel, Switzerland-based company said today at the Alzheimer’s Association International Conference in Copenhagen. Roche has yet to decide whether to begin the final, most expensive stage of patient tests required for approval.
The findings are the latest that suggest that doctors need to treat Alzheimer’s patients earlier, perhaps before symptoms appear. Today’s research provides some indication that the medicine may help those whose brains haven’t yet been as damaged by the disease, Roche said, citing data from both studies. The hypothesis of early treatment should be tested, said doctors who weren’t involved in the trials.
“This drug has zero chance of getting approved to treat mild to moderate Alzheimer’s,” said P. Murali Doraiswamy, a professor at Duke University who runs a patient trial unit focused on the aging brain. “The effect seems very small for what would surely be an expensive drug.”
Roche shares fell on the data, declining 0.6 percent to close at 266.40 Swiss francs in Zurich. The stock had been up as much as 0.9 percent before the results came out.
Failure in mild-to-moderate Alzheimer’s doesn’t rule out success in people who are likely to develop the disease and aren’t showing symptoms yet, Doraiswamy said. There’s also a chance for success in a separate Alzheimer’s prevention trial, begun in collaboration with the U.S. National Institutes of Health last year, Doraiswamy said.
The hint of an early treatment benefit emerged in tests for cognitive decline, not day-to-day tasks. There were also five deaths among patients who took crenezumab during the trial. Although researchers said the deaths probably aren’t linked to Roche’s experimental drug, regulators will take a careful look at them, Doraiswamy said.
The results are worth exploring in a bigger group of patients with mild Alzheimer’s, said Jeffrey Cummings, director of the Cleveland Clinic Lou Ruvo Center for Brain Health, who presented today’s results.
“For a phase two study where you’re just trying to decide whether a drug program should be continued, this is promising enough to be further explored,” Cummings said in a telephone interview.
Drugmakers generally don’t take a compound into the final phase of trials without a 60 percent to 70 percent chance of success, Tim Anderson, a New York-based analyst for Sanford C. Bernstein & Co., wrote in a note to investors. Crenezumab and its ilk fall far short of that, Anderson wrote.
“What drives this?” the analyst wrote. “The tremendous size of commercial opportunity. As we have shown previously, a drug that successfully modifies Alzheimer’s disease progression could make Lipitor (sales peaked at about $12 billion) look like a mid-sized product.”
The number of Americans with Alzheimer’s will probably rise from about 5 million to some 16 million by 2050, according to the Alzheimer’s Association.
Eli Lilly & Co. chose last year to test its similar drug, solanezumab, in patients with mild Alzheimer’s disease after seeing it fail in broader trials.
Both medicines target beta amyloid, a plaque build-up in patients’ brains. The hypothesis is that clearing the plaque -- or preventing it from forming in the first place -- could forestall brain damage and ultimately cognitive decline, loss of function and dementia. Beta amyloid isn’t the only potential culprit, however. Tangles of tau, another protein, have also been linked to the disease.
As in the Eli Lilly trials, there may be cause in Roche’s results for “cautious optimism” on very early treatment, said Ronald Petersen, director of the Alzheimer’s Disease Research Center at the Mayo Clinic in Rochester, Minnesota.
“You’d like to see a stronger signal to give you more encouragement, I guess, but I would not abandon the drug based on these results,” Petersen said in a telephone interview. “We may just be treating the disease too late. It’s like, ‘I’m going to lower my cholesterol after I have my heart attack.’ Well, you should’ve lowered it 15 years before.”
Petersen is among doctors consulting on the NIH-affiliated trial to see whether crenezumab, which can be infused or injected, can prevent Alzheimer’s in people in Colombia who are almost certain to develop the disease in their 40s because of a gene mutation. That study is sponsored by Roche’s U.S.-based Genentech unit and the Banner Alzheimer’s Institute. Novartis AG, Roche’s cross-town rival in Basel, also announced yesterday it would work with Banner to test two drugs for Alzheimer’s in patients without symptoms.
Today’s results will encourage scientists to keep looking earlier and point to a need for research that isn’t based on amyloid alone, said Maria Carrillo, a vice president of the Alzheimer’s Association.
“This is uncharted territory,” Carrillo said.
Genentech licensed crenezumab from Swiss biotechnology company AC Immune. Today’s patient-function results were from studies dubbed Abby and Blaze. Full results including biomarker data from Blaze, which was designed primarily to show whether crenezumab could remove amyloid from the brain, are due at the Clinical Trials on Alzheimer’s Disease conference in November, Cummings said.