Pyruvate kinase (PK) deficiency is an autosomal recessive disease caused by mutations in the PKLR gene that lead to reduced red blood cell PK (PK-R) enzyme activity. This rare hereditary glycolytic enzymopathy, with over 300 causative PKLR mutations identified to date, results in defective red blood cell glycolysis and hemolytic anemia. While the clinical presentation is variable, patients with PK deficiency may experience symptoms of hemolytic anemia, most commonly fatigue (sometimes extreme), jaundice, and dyspnea. No disease-specific therapy currently exists and treatment is limited to supportive care, including red blood cell transfusions, splenectomy/cholecystectomy, and iron chelation. Affected neonates may need phototherapy or exchange transfusions for severe hyperbilirubinemia. Allogeneic stem cell transplantation may cure the disease but experience is limited and the outcome is variable. Due the rarity of PK deficiency, its prevalence, clinical burden, and long-term clinical course are not well defined.
To address this gap, Boston Children's Hospital is nearing completion of the observational PK deficiency Natural History Study (ClinicalTrials.gov NCT02053480; N=254) to better understand the natural history and clinical burden of the disease. This longitudinal analysis (2-year follow-up) will report on PK deficiency-related signs, symptoms, and treatment outcomes. In order to continue and expand upon the collection of longitudinal data for PK deficiency, the Pyruvate Kinase Deficiency Global Longitudinal Registry (the PEAK Registry; NCT03481738) was developed. This registry study is a global, longitudinal, observational study for adult and pediatric patients with PK deficiency. Its primary objective is to record the natural history, treatment, outcomes, variability in clinical manifestations, and disease burden of patients with PK deficiency. Secondary objectives include data collection to assess the prevalence, incidence, and complications associated with PK deficiency; evaluate pregnancy outcomes; and investigate possible phenotype-genotype correlations. The study also aims to provide longitudinal data to assist physicians with the clinical management of individual patients. In order to maximize the amount of longitudinal data available, a novel data management system is being employed to harmonize Natural History Study and PEAK Registry data.
Approximately 500 patients will be enrolled over 7 years at an estimated 60 study centers in up to 20 countries in the 9-year study. All enrolled patients will be followed prospectively for at least 2 years and up to 9 years. Site and patient recruitment began in 2018. As of July 2019, 43 sites in 11 countries are active (Figure) and site recruitment has begun in Thailand, South Korea, and Australia. An update on patient enrollment will be provided.
Disclosures
Grace: Agios Pharmaceuticals, Inc: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Research Funding. Bianchi:Agios Pharmaceuticals, Inc.: Consultancy. Glader:Agios Pharmaceuticals, Inc: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Glenthøj:Celgene: Consultancy; Novo Nordisk: Honoraria; Alexion: Research Funding; Novartis: Consultancy; Agios Pharmaceuticals, Inc.: Consultancy. Jones:Agios Pharmaceuticals, Inc.: Employment, Equity Ownership. Kanno:Agios Pharmaceuticals, Inc.: Honoraria. Kuo:Pfizer: Consultancy; Novartis: Consultancy, Honoraria; Celgene: Consultancy; Bluebird Bio: Consultancy; Bioverativ: Other: Data Safety Monitoring Board; Agios: Consultancy; Alexion: Consultancy, Honoraria; Apellis: Consultancy. Layton:Novartis: Membership on an entity's Board of Directors or advisory committees; Agios: Membership on an entity's Board of Directors or advisory committees; Cerus Corporation: Membership on an entity's Board of Directors or advisory committees. van Beers:Pfizer: Research Funding; RR Mechatronics: Research Funding; Agios Pharmaceuticals, Inc.: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Research Funding. Xu:Agios: Employment, Equity Ownership.
An Ongoing Global, Longitudinal, Observational Study of Patients with Pyruvate Kinase Deficiency: The PEAK Registry
