Baxter International acknowledged today that its Phase III drug candidate Gammagard (immunoglobulin) failed to meet its co-primary endpoints of reducing cognitive decline and preserving functional abilities in patients with mild to moderate Alzheimer’s disease.
According to topline results released by Baxter, patients with mild to moderate Alzheimer’s who took Gammagard at either the 400 mg/kg or 200 mg/kg dose did not demonstrate a statistically significant difference in the rate of cognitive decline as compared to placebo. Those means stood at 7.4 for the 400 mg/kg patients, 8.9 for 200 mg/kg patients, and 8.4 for placebo patients. Results also showed a lack of statistically significant change in functional ability compared with placebo—means were -11.4 among both 400 mg/kg and placebo patients, rising slightly to -12.4 for 200 mg/kg patients.
But as Abbott acknowledged in a statement, the study was not powered to show statistical significance among subgroups. And instead of ending its clinical study of the experimental drug, however, Baxter cited a proverbial silver lining in the cloud of data released on Gammagard.
Patients with moderate Alzheimer’s, and carriers of the ApoE4 genetic marker—which increases risk of developing the disease—who were dosed at 400 mg/kg, showed cognition improvement of between 16% and 29% after taking the experimental drug vs. placebo, as measured by the Alzheimer’s Disease Assessment Scale—Cognitive Subscale (ADAS-Cog) and Modified Mini-Mental State (3MS) examination.
“The study missed its primary endpoints. However, we remain interested by the prespecified subgroup analyses, particularly among patients with moderate disease and those who carry a genetic risk factor for Alzheimer’s disease, two patient groups that are in great need of advances in care,” Ludwig Hantson, Ph.D., president of Baxter’s BioScience business, said in the statement. “A detailed analysis of the results from the GAP study continues, and we look forward to a greater understanding of the full dataset.”
The Phase III results came from the Gammaglobulin Alzheimer’s Partnership study conducted by Baxter with the Alzheimer’s Disease Cooperative Study, a clinical trial consortium supported by NIH’s National Institute on Aging.
The results contrast with promising Phase II findings for Gammagard released in July 2012. They showed improvements in thinking, behavior, and routine day-to-day functions in 11 of 16 patients receiving the drug for three years. Four patients who received the most effective dose of 0.4 g/kg experienced no decline in cognition, daily functioning, memory, and mood.
Gammagard joins a growing number of Alzheimer’s drug candidates in failing pivotal-stage clinical trials despite much optimism last year. Last year, Eli Lilly endured two Phase III flops for solanezumab, an amyloid beta monoclonal antibody that failed in effectiveness against beta-amyloid plaques. Solanezumab did not meet both cognitive and functional primary endpoints in two Phase III EXPEDITION trials.
Both EXPEDITION trials showed no statistically significant slowing of cognitive decline in patients with moderate Alzheimer’s. Lilly cited a prespecified secondary subgroup analysis in patients with mild Alzheimer’s disease, which showed a statistically significant reduction in cognitive decline. Even when Lilly modified EXPEDITION2 to specify a single primary endpoint of cognition, the revised endpoint did not achieve statistical significance.
However, Lilly said in December it plans to launch by Q3 a new Phase III study of the drug in patients with mild Alzheimer’s.
Also last year, Johnson & Johnson’s Janssen Alzheimer Immunotherapy unit and Pfizer ended development of Alzheimer’s drug candidate bapineuzumab after it failed to meet co-primary clinical endpoints in one Phase III study of patients who are ApoE4 carriers (Study 302), and another Phase III study of noncarriers (Study 301). J&J took a $700 million in-process R&D charge in Q3 2012.
And early in 2012, Pfizer wrote down $225 million in up-front cash and $500 million in potential milestone payments after Dimebon (latrepirdine), an Alzheimer’s drug developed with Medivation, flunked a Phase III study in patients with mild to moderate Alzheimer’s who were also being treated with donepezil HCL tablets. Dimebon failed to meet endpoints for cognitive improvement as well as for self-care and daily function.