“These top-line results indicate a potential benefit of this plasma protein fraction in slowing the progression of cognitive decline in patients with mild to moderate Alzheimer’s disease,” Karoly Nikolich, the chief executive officer of Alkahest, said in a press release.
Proteins found in the circulatory system were previously shown to alter motor and cognitive function. GRF6019 is a blood plasma-derived protein developed by Alkahest, in collaboration with Grifols, to treat neurodegenerative disorders.
In animal models, treatment with GRF6019 increased the number of neurons and improved age-related problems in learning and memory, while halting inflammation.
The Phase 2 trial (NCT03520998) assessed the safety, tolerability, and efficacy of GRF6019. The study enrolled 40 patients with mild to moderate Alzheimer’s disease, who were randomized to receive one of two doses of GRF6019 — a high (100 mL) or a low (250 mL) dose. The therapy was given once a day, directly into the vein, for five consecutive days during the first week. The same scheme was repeated during week 13.
At the end of the six-month study, researchers assessed the therapy’s safety by measuring the incidence of treatment-related adverse events. Additional objectives included efficacy parameters, such as changes in scores on the 11-item Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADASCog/11) and clinical dementia rating scale.
Top-line results showed that GRF6019 was safe and well-tolerated, the study’s primary goal. Moreover, patient’s cognitive function was maintained over the six months, as shown by scores in the ADASCog/11 and the Mini-Mental State Examination. These scores “would be expected to decline in this timeframe,” Alkahest states in the release.
A “negligible decline” in treated patients was seen in two other scaled tests, the 23-item AD Cooperative Activities of Daily Living and the Clinical Dementia Rating scale Sum-of-Boxes.
“Developing impactful treatments for this disease and other neurodegenerative diseases of aging has proven unsuccessful for decades. GRF6019 represents an innovative approach to effectively treating Alzheimer’s disease by targeting multiple underlying mechanisms of disease, and these data support the continued development of GRF6019 and other plasma protein fractions in Alzheimer’s disease,” Nikolich said.
A separate Phase 2 clinical trial (NCT03765762) is currently recruiting 20 people with severe Alzheimer’s disease to assess the safety and tolerability of GFR6019, and to measure its effects on patients’ mental state and capacity to perform daily activities.
Those enrolled in this randomized and placebo-controlled, nine-week study will be given either daily intravenous infusions of GRF6019 (250 mL) or of a placebo for five consecutive days, then followed for up to nine weeks. The trial is being conducted at sites in Arizona, Florida and California; more information is available here.