Background

GRF6021 is a proprietary plasma fraction, developed by Alkahest and manufactured by Grifols. Its development follows GRF6019, a fraction in Phase 2 testing for Alzheimer’s disease. This treatment approach grows out of mouse parabiosis studies indicating a rejuvenating effect of young blood on the aging brain (e.g., Nov 2009 news; May 2014 conference news), and clinical research infusing young adult plasma to treat age-related neurodegenerative disease (see Young Plasma). The rationale behind GRF6021 is that the components of young blood that counteract inflammatory and other degenerative processes in the brain can be enriched from pooled plasma and delivered as a standardized product. The manufactured plasma fractions have clotting factors and immunoglobulins removed, which improves their safety. Matching donor and recipient blood type is not required.

Findings

In November 2018, a six-month, Phase 2 trial began to test GRF6021 in people with Parkinson’s disease and mild cognitive impairment or Parkinson’s disease dementia. The 79 participants were randomized 2:1 to daily infusions of 250 mg GRF6021 or placebo for five consecutive days, followed by a second five-day dosing period three months later. The primary endpoint was safety. Secondary endpoints include measures of cognition, daily function and clinical severity. The trial, at 29 sites in the U.S., Australia, and France, finished in July 2020. According to results presented at the March 2021 AD/PD conference, the trial met its primary safety endpoint. No serious adverse events were attributed to GRF6021, and more than 80 percent of participants completed both infusion regimens. Headache and falls were more common in the GRF6021 group compared to placebo. The trial reported improvements in some secondary endpoints. The Montreal Cognitive Assessment and the PDQ-39 quality of life measure showed small but statistically significant improvements from baseline, while the placebo group did not change. Measures of executive function and digital clock drawing improved, but the changes did not reach statistical significance.

For details on GRF6021 trials, see clinicaltrials.gov.