Dr. Sperling and colleagues noted that several risk factors were associated with the occurrence of vasogenic edema, such as dose and APOE ε4 carrier status. Eleven of the 12 patients who developed vasogenic edema were treated with high-dose bapineuzumab (1 to 2 mg/kg), and one was treated with low-dose bapineuzumab (0.15 to 0.5 mg/kg). In addition, 10 of the 12 patients were APOE ε4 carriers. The researchers also found that the presence of microhemorrhage at baseline was a predictor of vasogenic edema.
In most subjects, vasogenic edema resolved on follow-up MRI within three months. Six patients were subsequently re-dosed at 0.5 mg/kg, and none had recurrence of vasogenic edema.
“Although the pathophysiology of vasogenic edema remains to be fully elucidated, the association with the APOE ε4 allele suggests that vasogenic edema may be related to vascular amyloid deposition,” said the researchers. Dr. Sperling explained that APOE ε4 carriers have a high vascular amyloid burden, and evidence of vascular amyloid burden has been found in the same regions where microhemorrhages tend to develop.
Phase III Study
Four phase III studies are now under way—two in carriers and two in noncarriers of the APOE ε4 allele. Dr. Sperling noted that the phase III protocol was recently amended to discontinue use of the 2-mg/kg dose of bapineuzumab in noncarriers. This decision was made by the study’s independent Safety Monitoring Committee due to the high occurrence of vasogenic edema in the highest-dose group. Participants originally assigned to the 2-mg/kg dose will be reassigned to the 1-mg/kg dose, and treatment with the 0.5- and 1-mg/kg doses will continue as planned. No changes have been made to the APOE ε4 carrier studies.
—Karen L. Spittler