The results

Grifols just presented the latest and complete results of its breakthrough Alzheimer's disease clinical study AMBAR (Alzheimer Management by Albumin Replacement) at the Clinical Trials on Alzheimer's Disease (CTAD) Conference in San Diego, Calif., USA. 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 CTAD 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 Alzheimer's Association International Conference (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.

Finally, Grifols presented new neuroimaging data at the CTAD in San Diego 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).

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.