Phase I results move Alzheimer’s candidate drug aducanumab into phase III trials
AT CTAD
Open-label extension results
Dr. Haeberlein focused on the subsequent 12-month, open-label extension trial, which enrolled 117 of the randomized cohort. In this study, patients who had been taking placebo were switched to either 3- or 6-mg/kg aducanumab. Patients who had taken 1 mg/kg were switched to 3 mg/kg. By the end, the remaining patients had taken the antibody for 2 years.
By 24 months, all the dosing groups showed a continued, linear reduction of amyloid plaques. Even those who switched from placebo to 3 mg/kg started to experience plaque reduction, although of a lesser magnitude than with the higher doses.
While still expressing caution, Dr. Haeberlein framed the CDR-SB results as very positive. The placebo and 1-mg/kg switchers continued to progress, but for those who continued on the 3-, 6-, and 10-mg/kg doses, “we saw a saw a numerical slowing of disease progression at both 18 and 24 months.”
However, none of the changes in CDR-SB scores reached statistical significance.
The numbers were somewhat more encouraging in the MMSE analysis. The 3- and 10-mg/kg groups began to separate at 12 months. By 24 months, the 10-mg/kg group had lost about 1 point on the MMSE while there were declines of about 2 points in the 3-mg/kg group and about 3 points in the 1-mg/kg group. Again, the 6-mg/kg group was an outlier, losing about 5 points.
“We already observed that this group behaved differently at 12 months on this endpoint, and we saw that particular cohort continued to follow that trend,” Dr. Haeberlein said.
There were 16 cases of ARIA in the extension trial. Eight were ARIA accompanied by vascular edema (ARIA-E) and these all occurred in the placebo and 1-mg/kg switchers. Three patients discontinued due to ARIA-E.
The remaining eight cases of ARIA were accompanied by microhemorrhage (ARIA-H); these were distributed among all of the dosage groups.
One patient with ARIA-E experienced a seizure and transient loss of pulse. Dr. Haeberlein didn’t elaborate on the possible cause of this event. Two additional patients died, with neither death judged related to the study medication.
The safety data, combined with the reduction of amyloid plaque and hints of cognitive and functional benefit, are enough to continue developing aducanumab, Dr. Haeberlein said. Biogen is recruiting 2,700 subjects with mild cognitive impairment or mild Alzheimer’s for identical phase III studies dubbed ENGAGE and EMERGE.
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