Dr. Stephen Salloway pulls no punches in describing the results of two clinical trials of the Alzheimer’s drug bapineuzumab that he helped to lead. The antibody failed to produce cognitive improvement for volunteers compared to a placebo, he and colleagues report Jan. 23 in the New England Journal of Medicine.
Looking for a breakthrough
“The biggest disappointment from this trial, was that if we had shown benefit with a drug like bapi, it would give people hope that Alzheimer’s is a treatable disease, that we can slow it down,” Salloway said.
That much needed breakthrough could come from new trials that apply the lessons researchers learned. It is likely that many of the participants, for example, had some form of dementia other than Alzheimer’s disease, Salloway said. A future trial should only include those with amyloid buildup confirmed by a PET scan and spinal fluid testing.
“We were surprised to find that overall 20 percent of participants in both the bapi and solanezumab trials did not meet the threshold for amyloid buildup,” Salloway said. “That proportion was higher for ApoE4 noncarriers.”
Also amyloid plays a more critical role early in the development of the disease, he said. Trials that administer the medication earlier could produce greater effects.
It would make sense, he said, to pair drugs like bapi with drugs such as a beta secretase inhibitor that maximize amyloid lowering. The safety of such a combination, or combination with drugs that address the tangles of tau proteins also found in Alzheimer’s, is not known, Salloway said, but needs to be carefully tested.
“Without taking strategic risks, we aren’t going to make the progress we need to move forward,” he said.
Testing drug combinations, however, may require pharmaceutical companies to pool resources and share data. He acknowledged that’s something competitors are usually reluctant to do. These partnerships are forming in the pre-competitive arena, he said, but need to be expanded into clinical trials.
“For the level of suffering with this disease and for our economy, we have to break down some barriers and come up with innovative approaches.”
