New data from AMBAR trials testing the efficacy and safety of short-term plasma exchange followed by long-term plasmapheresis with infusion of Human Albumin combined with intravenous immunoglobulin in patients with mild and moderate Alzheimer’s disease (AD) were presented, by Grifols, at the 2019 International Congress on AD and Parkinson’s disease (PD) in Lisbon, Portugal.
AMBAR is based on the hypothesis that most of the amyloid-beta protein (Aβ) is bound to albumin and circulates in plasma. Extracting this plasma may remove pathological substances, such as Aβ, from the brain and potentially limiting the disease’s impact on the patient’s cognitive functions.
In previous result presentation at the 12th Clinical Trials on Alzheimer’s Disease congress (CTAD) in October 2018 in Barcelona, Grifols, showed that in the re-specified cohort of moderate AD patients demonstrated a statistically significant reduction of 61% in disease progression in both AD Assessment Scale-cognitive (ADAS-Cog) and the AD Cooperative Study – Activities of Daily Living (ADCS-ADL) scales of treated patient compare to placebo at 14 months.
The new data presented from Grifols, showed that in the secondary endpoints in all patient analysis there were statistically significant improvement in memory, language, processing, speed and quality of life (QoL) of High-Albumin+Intravenous immunoglobulin (IVIG) arm compare to placebo at 14 months. In the cohort of mild AD there were also statistically significant improvement in language and processing speed with high-albumin+IVG, while in the moderate AD cohort statistically significant improvement were found in memory and QoL.
Safety data show low adverse events (AEs) rate through the whole study related to plasma exchange and AEs were largely accumulated during the conventional therapeutic plasma exchange (TPE) period with a progressive decrease during the low-volume PE period (LVPE). Patients treated with plasmapheresis without IVIG had more infections than the patients treated with IVIG and also than those in placebo arm, however, the rate of infections not related with caterer was lower in patient receiving IVIG.
Furthermore, cerebrospinal fluid (CSF) Aβ42 biomarkers showed stabilization in treated patient and decline in placebo arm particularly for moderate AD, while CSF Tau and P-Tau showed less increase in the treated patients compared to placebo particularly for moderate AD.
After all the failures in the AD pipeline especially in AD drug targeting the amyloid pathways, such as Roche’s crenzumab and Biogen/Eisai aducanumab, the most promising drug in the AD pipeline, finally positive clinical data that gives hope to treat this disease. Albumin may represent a multi-modal approach to the management of the disease due to its binding capacity, antioxidant, and immune modulatory and anti-inflammatory properties.
However, this drug is not approved yet and it will take many years to explore if patients will really benefit from the treatment. The company has not yet decided in which way to submit approval to regulatory advisors as this can be done in 2 different options, first submit it as a plasma changes procedure that is regulated by medical regulation (ASFA) or second, submit the approval of the drug to the regulatory FDA.
Grifols will continue its clinical programme and they will conduct a new big trial even though it is not that clear which cohort they will study if mild or moderate AD. At The Alzheimer’s Association International Conference(AAIC) held from July 14-17 in Los Angeles, the company will present another update about the clinical endpoints and all biomarkers of the study and they will completed also all protocol data by the end of this year.