GRF6021 / Grifols - LARVOL DELTA

Cognitive Impairment in Parkinson's Disease: An Updated Overview Focusing on Emerging Pharmaceutical Treatment Approaches. (PubMed, Medicina (Kaunas)) - "Accumulating preclinical and clinical evidence shows that several agents may provide beneficial effects on patients with PD and cognitive impairment, including ceftriaxone, ambroxol, intranasal insulin, nilotinib, atomoxetine, mevidalen, blarcamesine, prasinezumab, SYN120, ENT-01, NYX-458, GRF6021, fosgonimeton, INT-777, Neuropeptide S, silibinin, osmotin, cordycepin, huperzine A, fibroblast growth factor 21, Poloxamer 188, ginsenoside Rb1, thioredoxin-1, tangeretin, istradefylline and Eugenia uniflora. In this updated overview, we aim to cover the clinical aspects of the spectrum of PD-related cognitive impairment and discuss recent evidence on emerging treatment approaches that are under investigation at a preclinical and clinical level. Finally, we aim to provide additional insights and propose new ideas for investigation that may be feasible and effective for the spectrum of PD-related cognitive impairment."

Journal • Review • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Inflammation • Movement Disorders • Parkinson's Disease • FGF21

Perioperative Administration of A Human Plasma Fraction Modulates the Inflammatory Response to Surgery And Favors Clinical Recovery (ASA 2023) - "The alterations of the immune response on postoperative day 1 by GRF6021 echoed the proteomic findings (AUC = 0.70)(p=0.02), including a reduction of pSTAT3 signaling in sentinel T cell populations (Figure 2)...Results are consistent with those reported in preclinical studies, indicating that plasma protein fractions enriched in the young exert clinically beneficial regenerative effects. Considering >2 million major joint replacement surgeries per year in the US alone and its safety profile, GFR-6021 could benefit and impact postoperative recovery in large and aging patient populations."

Clinical • Surgery • Alzheimer's Disease • Cognitive Disorders • Fatigue • Inflammation • Orthopedics • Pain

Perioperative Administration of A Human Plasma Fraction Modulates the Inflammatory Response to Surgery And Favors Clinical Recovery (ASA 2023) - "The alterations of the immune response on postoperative day 1 by GRF6021 echoed the proteomic findings (AUC = 0.70)(p=0.02), including a reduction of pSTAT3 signaling in sentinel T cell populations (Figure 2)...Results are consistent with those reported in preclinical studies, indicating that plasma protein fractions enriched in the young exert clinically beneficial regenerative effects. Considering >2 million major joint replacement surgeries per year in the US alone and its safety profile, GFR-6021 could benefit and impact postoperative recovery in large and aging patient populations."

Clinical • Surgery • Alzheimer's Disease • Cognitive Disorders • Fatigue • Inflammation • Orthopedics • Pain

MRI FINDINGS FROM THE ALK6021-201 STUDY IN PARKINSON’S DISEASE PATIENTS (ADPD 2022) - "Repeat infusions of GRF6021 for 5 consecutive days approximately every 3 months was associated with structural, functional, and vascular MRI biomarker improvements compared to placebo when assessed at day 90 follow-up."

Clinical • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Immunology • Movement Disorders • Parkinson's Disease

A Study to Evaluate the Effect of GRF6021 on Postoperative Recovery Following Primary Hip or Knee Arthroplasty (clinicaltrials.gov) - P2; N=38; Completed; Sponsor: Alkahest, Inc.; Active, not recruiting ➔ Completed

Clinical • Trial completion • Orthopedics

Treatment of Parkinson's Disease with Cognitive Impairment: Current Approaches and Future Directions. (PubMed, Behav Sci (Basel)) - "The only recommended treatment for PDD currently is rivastigmine, a cholinesterase inhibitor. Donepezil and galantamine-other cholinesterase inhibitors-are possibly useful...Drug repurposing (atomoxetine, levodopa, insulin, atomoxetine for PD-MCI; ambroxol and ceftriaxone for PDD) and novel medications (SYN120, GRF6021, NYX-458 for PD-MCI; ANAVEX2-73, LY3154207, ENT-01, DAAOI-P for PDD) currently have insufficient evidence. There is growing research supporting exercise in the treatment of PD-MCI, but most non-pharmacological approaches have insufficient evidence for use in PD-MCI (cognitive rehabilitation, deep brain stimulation, transcranial direct current stimulation, transcranial ultrasound, vestibular nerve stimulation) and PDD (cognitive intervention, deep brain stimulation, transcranial alternating current stimulation, transcranial ultrasound, temporal blood brain barrier disruption). Research is needed for both disease-modifying and symptomatic treatments in PD..."

Journal • Review • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Immunology • Movement Disorders • Parkinson's Disease

Safety and Tolerability of GRF6019 Infusions in Severe Alzheimer's Disease: A Phase II Double-Blind Placebo-Controlled Trial. (PubMed, J Alzheimers Dis) - "GRF6019 demonstrated excellent safety, feasibility, and tolerability. Future trials designed to characterize the potential functional benefits of GRF6019 and related plasma fractions in severe AD are warranted."

Clinical • Journal • P2 data • Alzheimer's Disease • CNS Disorders • Dementia • Hypertension • Hypotension • Immunology • Inflammation

Alkahest to Present Positive Data from Completed Phase 2 Clinical Trial at the 15th International Conference on Alzheimer’s and Parkinson’s Disease (GlobeNewswire) - "Alkahest...announced it will be delivering a presentation of data from a completed study of its therapeutic plasma fraction candidate, GRF6021, in subjects with Parkinson’s disease (PD) and cognitive impairment at the virtual 15th International Conference on Alzheimer’s and Parkinson’s Diseases."

P2 data • CNS Disorders • Cognitive Disorders • Parkinson's Disease

[VIRTUAL] A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL ASSESSING THE SAFETY AND TOLERABILITY OF GRF6021 IN SUBJECTS WITH PARKINSON’S DISEASE AND COGNITIVE IMPAIRMENT (ADPD 2021) - "The trial was not statistically powered to detect differences in secondary efficacy endpoints; however, numerical superiority of GRF6021 over placebo was observed on multiple cognitive endpoints.  Conclusions This trial met its primary endpoint by demonstrating that daily infusions of GRF6021 for 5 consecutive days at 3-month intervals were safe and well tolerated. Secondary endpoints indicated that GRF6021 may have cognitive benefits and future development in PD with cognitive impairment is planned."

Clinical • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Immunology • Inflammation • Movement Disorders • Parkinson's Disease

[VIRTUAL] EFFICACY OF A NOVEL HUMAN PLASMA THERAPEUTIC IN A MOUSE MODEL OF ALZHEIMER’S DISEASE (ADPD 2021) - "We have developed two therapeutic plasma fractions derived from healthy human donors, GRF6019 and GRF6021, that show beneficial effects on symptoms of aging. Treatment of P301S mice with a human plasma fraction ameliorates multiple AD-related symptoms, including deficits in cognition and neuronal activity, microgliosis, and tau pathology. These results demonstrate the potential of plasma fractions to transform approaches and support the advancement of GRF6021 to clinical testing for AD."

Preclinical • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Immunology • Inflammation

A Study to Evaluate the Effect of GRF6021 on Postoperative Recovery Following Primary Hip or Knee Arthroplasty (clinicaltrials.gov) - P2; N=45; Active, not recruiting; Sponsor: Alkahest, Inc.; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed • Orthopedics

A Study to Evaluate the Effect of GRF6021 on Postoperative Recovery Following Primary Hip or Knee Arthroplasty (clinicaltrials.gov) - P2; N=45; Recruiting; Sponsor: Alkahest, Inc.; Trial completion date: Oct 2020 ➔ Jan 2021; Trial primary completion date: Oct 2020 ➔ Jan 2021

Clinical • Trial completion date • Trial primary completion date • Orthopedics

A Study to Assess the Safety of GRF6021 Infusions in Subjects With Parkinson's Disease and Cognitive Impairment (clinicaltrials.gov) - P2; N=79; Completed; Sponsor: Alkahest, Inc.; Active, not recruiting ➔ Completed; Trial completion date: Nov 2020 ➔ Jul 2020

Clinical • Trial completion • Trial completion date • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Movement Disorders • Parkinson's Disease

Grifols Moves Deeper Into Proteome R&D With $146M Deal for Alkahest (Xconomy) - "Alkahest, a company that analyzes blood proteins to develop therapies that address neurological disorders including Alzheimer’s disease, is set to be acquired by partner Grifols in a $146 million deal.....Alkahest drug candidates, GRF-6019 and GRF-6021, are intended to enhance the growth and development of nerve tissue, improve the deficits in learning and memory that come with aging, and reduce neuroinflammation....The other Alkahest lead compound, GRF-6021, is being evaluated in separate a Phase 2 study in Parkinson’s disease. The company’s pipeline also includes AKST4290, in mid-stage tests for the wet form of age-related macular degeneration as well as Parkinson’s..."

M&A • Alzheimer's Disease • CNS Disorders • Parkinson's Disease

A Study to Evaluate the Effect of GRF6021 on Postoperative Recovery Following Primary Hip or Knee Arthroplasty (clinicaltrials.gov) - P2; N=45; Recruiting; Sponsor: Alkahest, Inc.; Trial primary completion date: Jul 2020 ➔ Oct 2020

Clinical • Trial primary completion date

A Study to Assess the Safety of GRF6021 Infusions in Subjects With Parkinson's Disease and Cognitive Impairment (clinicaltrials.gov) - P2; N=90; Active, not recruiting; Sponsor: Alkahest, Inc.; Trial primary completion date: Nov 2020 ➔ Jul 2020

Clinical • Trial primary completion date • Alzheimer's Disease • CNS Disorders • Gene Therapies • Movement Disorders • Parkinson's Disease • Reperfusion Injury

Alkahest Provides Corporate Update (GlobeNewswire) - "Alkahest, Inc., a clinical stage biotechnology company focused on discovering and developing transformative therapies to treat age-related diseases, today provided a corporate update....Ongoing Studies: AKST6021-201 (NCT03713957), a Phase 2 clinical trial of GRF6021 in patients with Parkinson’s disease with cognitive impairment; AKST4290-211 (TEAL) (NCT04369430), a Phase 2 clinical trial in patients with Parkinson’s disease."

Trial status • CNS Disorders • Cognitive Disorders • Parkinson's Disease

[VIRTUAL] EFFICACY OF A NOVEL HUMAN PLASMA THERAPEUTIC IN A MOUSE MODEL OF ALZHEIMER’S DISEASE (AAT-ADPD 2020) - "We have developed two therapeutic plasma fractions derived from healthy human donors, GRF6019 and GRF6021, that show beneficial effects on symptoms of aging. Treatment of P301S mice with a human plasma fraction ameliorates multiple AD-related symptoms, including deficits in cognition and neuronal activity, microgliosis, and tau pathology. These results demonstrate the potential of plasma fractions to transform approaches and support the advancement of GRF6021 to clinical testing for AD."

Preclinical

[VIRTUAL] EFFICACY OF A NOVEL HUMAN PLASMA THERAPEUTIC IN A MOUSE MODEL OF ALZHEIMER’S DISEASE (AAT-ADPD 2020) - "We have developed two therapeutic plasma fractions derived from healthy human donors, GRF6019 and GRF6021, that show beneficial effects on symptoms of aging. Treatment of P301S mice with a human plasma fraction ameliorates multiple AD-related symptoms, including deficits in cognition and neuronal activity, microgliosis, and tau pathology. These results demonstrate the potential of plasma fractions to transform approaches and support the advancement of GRF6021 to clinical testing for AD."

Preclinical

A Study to Assess the Safety of GRF6021 Infusions in Subjects With Parkinson's Disease and Cognitive Impairment (clinicaltrials.gov) - P2; N=90; Active, not recruiting; Sponsor: Alkahest, Inc.; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed

A Study to Evaluate the Effect of GRF6021 on Postoperative Recovery Following Primary Hip or Knee Arthroplasty (clinicaltrials.gov) - P2; N=45; Recruiting; Sponsor: Alkahest, Inc.; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open

Alkahest Announces Positive Top-line Data from Phase 2 Study in Mild to Moderate Alzheimer’s Disease (GlobeNewswire, Alkahest, Inc.) - SAN CARLOS, Calif., Aug 05, 2019 (GLOBE NEWSWIRE) -- Alkahest, Inc, a clinical-stage biotechnology company focused on developing transformative therapies to treat age-related diseases, today announced top-line data from its phase 2 clinical trial of its candidate GRF6019 in mild-to-moderate Alzheimer’s disease dementia (AD). The study was designed to evaluate the safety, tolerability, and potential therapeutic effects of multiple doses of GRF6019 in patients with mild-to-moderate AD over six months.

Clinical • Clinical data