Trial results showed a reduction of 61% in disease progression in both primary efficacy endpoints measuring cognition and activities of daily living at 14 months.
Merce Boada, MD, PhD
A recent analysis on Alzheimer Management by Albumin Replacement (AMBAR) data, presented at the Clinical Trials on Alzheimer’s Disease Congress in Barcelona, Spain, has shown positive, highly relevant results in a cohort of patients with moderate Alzheimer disease.
Based on the combination of plasmapheresis with Albutein 20%, AMBAR demonstrated a significant reduction in the progression of the disease in patients with moderate Alzheimer disease.
“We are very pleased with the results and we celebrate them as a breath of fresh air that brings hope to the Alzheimer’s patients and their families. This is the most significant development in the treatment of patients with moderate Alzheimer’s disease in over 15 years,” Mercé Boada, MD, PhD, Director of Fundació ACE, said in a statement. “As a clinician it is also important to note that this procedure is safe and feasible. We have conducted more than 1000 plasma exchanges in our center and close to 5000 in the total study.”
AMBAR, a randomized blinded and placebo controlled, parallel group phase 2b/3 clinical trial, that enrolled 496 mild and moderate participants with Alzheimer from 41 treatment centers in Europe and the United States, evaluated the safety and efficacy of short-term plasma exchange followed by long-term plasmapheresis with infusion of human Albumin combined with intravenous immunoglobulin. Participants, 55­—85 years old, were randomized to 1 placebo group and 3 treatment groups— plasma exchange with Albumin 20% and immune globulin intravenous (IGIV), high dose; plasma exchange with Albumin 20% and IGI, low dose; and plasma exchange with Albumin 20%, low dose. Treatment lasted 14 months and was divided into 2 phases: a 6-week initial phase common to all participants, followed by a 12-month second phase where different volumes and concentrations of Albumin were administered to different groups.
The trial was designed to evaluate whether the progression of Alzheimer could be stabilized through plasma exchange and is based on the hypothesis that most of the amyloid-beta protein is bound to Albumin and circulates in plasma.
The efficacy of treatment was evaluated by changes in cognition, assessed by the Alzheimer’s Disease Assessment Scale-cognitive (ADAS-Cog), and daily living activities scores assessed by the Alzheimer’s Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) scales at 14 months of treatment. Secondary outcome measures included cognition measured by ADAS-Cog and activities of daily living measured by ADCS-ADL at intermediate points along with other variables of function and cognition. The prespecified primary analysis performed on the study population included assessment of the differences to placebo in the primary outcomes of the following study arms: 3 combinations of plasmapheresis with Albumin 20% and IGIV replacement that shared the same volume of plasma removed regardless of the arm; an arm with all patients treated with plasmapheresis; and an arm that included all patients treated with plasmapheresis analyzed by disease severity.
The differences between the treatment arms and placebo showed between 50%­—75% less decline for the ADAS-Cog scale and between 42%–70% less decline for the ADCS-ADL scale in the treated participants. In the arm with all participants treated with plasma exchange the difference to placebo achieved a 66% less decline for the ADAS-Cog scale with a statistical significance of .06 and a 52% less decline for the ADCS-ADL scale with a statistical significance of .03.
In the treatment arm where all participants were treated with plasma exchanged analyzed by disease severity, those with mild Alzheimer did not decline, however, the same lack of progression was observed in the placebo for both ADAS-Cog and ADCS-ADL scales. According to Grifols, this suggests that more follow-up time is needed in order to observe disease progression in a milder state. Participants with moderate Alzheimer treated with plasma exchanged showed a 61% less decline compared to placebo across the primary efficacy endpoints measured by ADAS-Cog and ADCS-ADL scales with statistical significances of .05 and .002, respectively. Researchers also reported that moderate Alzheimer participants analyzed by plasma exchange combination type, all 3 combinations achieved statistical significance for ADCS-ADL.
Grifols demonstrates a significant reduction (61%) in the progression of moderate Alzheimer’s disease using its AMBAR treatment protocol [news release]. Barcelona, Spain: Grifols; Oct. 26, 2018. https://www.grifols.com/documents/10192/59655359/np-20181027-en/2919b97e-9f65-482c-a7e8-98be4db7559b. Accessed Oct. 30, 2018.