The AMBAR results

The AMBAR results

Grifols is presenting the latest results of its breakthrough Alzheimer's disease clinical study AMBAR (Alzheimer Management by Albumin Replacement) at the 2020 Alzheimer's Association International Conference (AAIC) virtual edition, July 27-31. New complementary results are aligned with those presented over the last year showing consistent response across all relevant endpoints. This concludes more than a year of encouraging results showing the reduction in the progression of the disease in patients with mild-to-moderate Alzheimer's.

Grifols presented the first AMBAR results at the 11th Clinical Trials on Alzheimer's Disease (CTAD) Conference in Barcelona, Spain, in October 2018. The primary efficacy endpoints – the ADAS-Cog1 and ADCS-ADL2 scales – showed a 61% reduction in disease progression for both measures in the cohort of patients with moderate Alzheimer's.

Secondary endpoints evaluating clinical progression and biomarkers were presented at the 14th International Conference on Alzheimer's and Parkinson's Diseases (AD/PD) in Lisbon, Portugal, in March 2019. Several neuropsychological tests assessing cognition, language and quality of life (RAVLT3, SDMT4, PVF5, QoL-AD6) showed a positive impact in memory and quality of life in patients with moderate Alzheimer's, and in language and processing speed in patients in a mild stage of the disease. Biomarkers measured in cerebrospinal fluid (CSF) showed a stabilization of Abeta 42 and P-Tau protein levels, which are associated with Alzheimer's.

Results of other relevant secondary endpoints – CDR-Sb7 and ADCS-CGIC8 – evaluating both functional and cognitive capacity were presented at the AAIC 2019 in Los Angeles, Calif., USA, in July. They also pointed in the same direction when considering all treated patients together.

The CDR-Sb scale – which assesses memory, orientation, judgment, community affairs, home and hobbies, and personal care – showed a 71% reduction in clinical decline with respect to placebo in patients treated as a whole and in all three clinical trial treatment arms analyzed separately.

For the ADCS-CGIC scale – which assesses several domains of cognition, daily functioning and behavior from both the patient and the caregiver perspective – a stabilization was observed in all treated patients with respect to placebo. This effect remained in all three clinical trial treatment arms when analyzed separately.

Neuroimaging data were presented at the CTAD in San Diego, Calif., USA, in December 2019. Neuroimaging, measured by the FDG-PET9 technique, showed positive results particularly in patients receiving both albumin and immunoglobulin. In comparison with the placebo group, these patients had less reduction of brain glucose metabolism over the 14 months of the clinical trial. This suggests less progression in neuronal damage in these patients (see infographic).

In line with Grifols' commitment to research, a scientific article with the main results has been published in Alzheimer's & Dementia: The journal of the Alzheimer's Association, the most influential journal in the Alzheimer's field (Boada, M., López, O. L., Olazarán, J., Núñez, L., Pfeffer, M., Paricio, M., Lorites, J., Piñol-Ripoll, G., Gámez, J. E., Anaya, F., Kiprov, D., Lima, J., Grifols, C., Torres, M., Costa, M., Bozzo, J., Szczepiorkowski, Z. M., Hendrix, S., & Páez, A. (2020). A randomized, controlled clinical trial of plasma exchange with albumin replacement for Alzheimer's disease: Primary results of the AMBAR Study. Alzheimer's & Dementia: The Journal of the Alzheimer's Association, Advance online publication. https://doi.org/10.1002/alz.12137).

The article shows that plasma exchange with albumin replacement was feasible and could slow cognitive and functional decline in patients with Alzheimer's over a period of 14 months. This was supported by the effects observed in the co-primary and global secondary assessment outcomes. Also, these findings have the potential to offer patients with Alzheimer's a new modality of treatment.

1 ADAS-COG: ALZHEIMER'S DISEASE ASSESSMENT SCALE-COGNITIVE.
2 ADCS-ADL: ALZHEIMER'S DISEASE COOPERATIVE STUDY-ACTIVITIES OF DAILY LIVING.
3 CDR-SB: CLINICAL DEMENTIA RATING SCALE-SUM OF BOXES.
4 ADCS-CGIC: ALZHEIMER'S DISEASE COOPERATIVE STUDY-CLINICAL GLOBAL IMPRESSION OF CHANGE.
5 RAVLT: REY AUDITORY VERBAL LEARNING TEST.
6 SDMT: SYMBOL DIGIT MODALITIES TEST.
7 PVF: PHONETIC VERBAL FLUENCY.
8 QoL-AD: QUALITY OF LIFE IN ALZHEIMER'S DISEASE.
9 FDG-PET: 18FLUORPDEOXYGLUCOSE- POSITRON EMISSION TOMOGRAPHY.

"Grifols will continue to explore the potential of plasma proteins and plasma exchange in further studies."

Víctor Grífols, Grifols Chairman

"The results are very encouraging and confirm our line of research."

Dr. Antonio Páez, M.D., Grifols Medical Director of the AMBAR Clinical Program

"This is the most significant development in the treatment of Alzheimer's disease I've seen in over 15 years. The results are extremely promising."

Dr. Mercè Boada M.D., Ph.D., Director of Fundació ACE., Barcelona, Spain.

"Those findings open new avenues for the research of neurodegenerative disorders that have the potential to offer a new modality of treatment."

Dr. Óscar López, Director of the Alzheimer Disease Research Center of the University of Pittsburgh, USA

"Grifols will continue to explore the potential of plasma proteins and plasma exchange in further studies."

Víctor Grífols, Grifols Chairman

"The results are very encouraging and confirm our line of research."

Dr. Antonio Páez, M.D., Grifols Medical Director of the AMBAR Clinical Program

"This is the most significant development in the treatment of Alzheimer's disease I've seen in over 15 years. The results are extremely promising."

Dr. Mercè Boada M.D., Ph.D., Director of Fundació ACE., Barcelona, Spain.

"Those findings open new avenues for the research of neurodegenerative disorders that have the potential to offer a new modality of treatment."

Dr. Óscar López, Director of the Alzheimer Disease Research Center of the University of Pittsburgh, USA