(In this July 24th story, corrects paragraphs 3 and 16 to clarify that Eisai executive said the trial generated positive, rather than effective, results at lower doses)
By Julie Steenhuysen and Deena Beasley
(Reuters) - Eisai Co Ltd and Biogen Inc will move forward with late-stage clinical trials of their Alzheimer’s disease drug, BAN2401, and are working with regulators to design the next studies and gain expedited review as a breakthrough therapy.
The companies announced this month that despite failing at an earlier stage, the drug slowed Alzheimer’s progression at its highest dose, providing renewed hope in a field littered with failures.
In interviews with Reuters, Japanese drugmaker Eisai said the treatment also generated positive trial results at lower doses. Full results will be presented on Wednesday at the Alzheimer’s Association International Conference in Chicago.
“Our plan would be to start more trials,” Dr. Lynn Kramer, chief medical officer of Eisai’s neurology unit, told Reuters. “Whether it be Phase III in the same patient population, or other populations. We are thinking about a number of things.”
Kramer said the company had already contacted various regulators and plans to pursue accelerated approvals. “We are certainly considering ‘prime’ status in Europe, ‘breakthrough’ in the United States and ‘sakigake’ in Japan,” he said of various paths to potentially swifter approvals.
The companies said after 18 months of treatment, patients who received the highest dose of BAN2401 saw a statistically significant improvement in cognitive and biological measures of Alzheimer’s versus placebo. That was a welcome surprise as the drug did not appear to be working at the 12-month mark.
The news marked a rare success for Alzheimer’s research following failure after failure of candidates from companies including Pfizer, Eli Lilly and Merck & Co. It also raised hope for aducanumab, another Biogen/Eisai drug in final stage testing. Both treatments are antibodies aimed at removing toxic clumps of amyloid from the brain.
Any successful Alzheimer’s treatment is virtually guaranteed to become a multibillion-dollar seller. Alzheimer’s, the most common form of dementia, affects nearly 50 million people worldwide and is expected to rise to more than 131 million by 2050, according to Alzheimer’s Disease International.
“All the chips are on the table with these two trials,” said Dr. Ronald Petersen, an Alzheimer’s expert from Mayo Clinic in Rochester, Minnesota.
One difference, experts say, is that the Eisai/Biogen drugs are among the first to use PET scans to ensure study participants all have amyloid in their brains. Many dementia patients in previous trials later proved not to have the amyloid plaques the experimental drugs targeted, greatly increasing the likelihood of failure.
The U.S. Food and Drug Administration has said it is open to trials that measure effects on biomarkers, such as beta amyloid, rather than symptoms like memory loss, to allow companies to test treatments much earlier in the disease.
The trial of 856 patients with early Alzheimer’s tested BAN2401 at five doses against placebo.
Participants were evaluated using an Eisai-devised tool that drew from three established Alzheimer’s assessment scales. Kramer said the custom endpoint was important as prior cognitive scales were developed for people with later-stage disease.
The trial also used an “adaptive” design that allowed Eisai to place new enrollees into groups receiving what appeared to be the most effective doses. Kramer would not reveal how many patients received the highest dose.
“We believe that there are plenty of patients at the higher doses. When people see the results, they will think so too,” he said.
While the news release only mentioned the highest dose, Kramer said positive results were seen for other doses. “There is a clear dose response,” he said.
The companies will likely face some skepticism. The 12-month results used a predictive “Bayesian” statistical method, while the 18-month results used traditional statistical methods to assess the drug.
Kramer said the goal at 12 months was to show an 80 percent probability that patients would be 25 percent better off at the end of the trial than those who got a placebo.
“This was a very complicated trial design. I’m not surprised that it didn’t work,” said Dr. Paul Aisen of the University of Southern California’s Alzheimer’s Therapeutic Research Institute.
Aisen said he wished they had used a more traditional design from the start. “Now we’re left having to worry about changing the analysis after seeing some of the results and what kind of bias they may have introduced.”
Any positive data out of these clinical trials “has to be a good thing, even if it’s small,” said Gareth Howell, an Alzheimer’s expert from The Jackson Laboratory in Maine.
Dr. Stephen Salloway, a Brown University neurologist and an investigator on the aducanumab trials, said the BAN2401 results provide “consistent evidence that this strategy could be effective.”
Kramer said there is no doubt the BAN2401 results are positive for aducanumab’s prospects. “It has a bigger positive implication for BAN2401,” he said.
Reporting by Julie Steenhuysen in Chicago and Deena Beasley in Los Angeles; Editing by Bill Berkrot