Contributions
Abstract: PB1966
Type: Publication Only
Background
Pyruvate kinase (PK) deficiency is a rare hereditary glycolytic enzymopathy caused by mutations in the PKLR gene, which lead to reduced red blood cell PK (PK-R) enzyme activity, resulting in defective red blood cell glycolysis and hemolytic anemia. It is the most common cause of glycolytic hemolytic anemia. Over 300 causative PKLR mutations have been identified to date. Patients with PK deficiency may experience symptoms of hemolytic anemia, most commonly fatigue (sometimes extreme), jaundice, dyspnea and weakness. Current treatment is limited to supportive care options. Affected neonates may need phototherapy or exchange transfusions for severe hyperbilirubinemia, while treatment strategies for adults can include red blood cell transfusions, splenectomy/cholecystectomy, and iron chelation, each of which is associated with some risk to the patient. No disease-specific therapy currently exists. The observational PK deficiency Natural History Study (NHS) conducted by Boston Children’s Hospital (ClinicalTrials.gov NCT02053480; N=258) initiated the longitudinal analysis (2-year follow-up) and reporting on PK deficiency-related signs, symptoms and treatment outcomes to better understand the natural history and clinical burden of the disease. The Peak Registry, a global, longitudinal, non-interventional study of PK deficiency, aims to build upon the NHS with additional patients and longer follow-up.
Aims
To report the design of the Peak Registry.
Methods
The Peak Registry is a global, longitudinal, observational registry for adult and pediatric patients with PK deficiency. The 9-year study will enroll approximately 500 patients over 7 years at an estimated 60 study centers in up to 20 countries. All enrolled patients will be followed prospectively for at least 2 years, and up to 9 years. Patients of all ages with a diagnosis of PK deficiency confirmed by genetic testing are eligible to enroll. Each patient or their parent/guardian must be willing and able to give written informed consent and/or assent. Patients who are actively enrolled in any Agios-sponsored clinical trial involving treatment with a PK activator will be excluded. Demographic, clinical, and treatment data, and other data relevant to the management of patients with PK deficiency, will be collected from participating registry physicians via electronic case report forms. The primary objective of the registry is to develop an understanding of the longitudinal clinical implications of PK deficiency, including natural history, treatment and outcomes, variability in clinical care, and disease burden. Secondary objectives include: to understand the prevalence, incidence, and severity of complications associated with PK deficiency; examine phenotype-genotype correlation; evaluate pregnancy outcomes; and provide longitudinal data to assist physicians with the clinical management of individual patients. Site and patient recruitment are ongoing. Study conduct, data analyses and reporting is governed by a steering committee comprised of experts involved in the research, diagnosis, and/or care of patients with PK deficiency in cooperation with the sponsor (Agios Pharmaceuticals, Inc.).
Results
Not yet available.
Conclusion
This non-interventional study aims to extend the work of the NHS with additional patients from an expanded geographic distribution and longer follow-up, to further improve the understanding of the complex clinical burden of PK deficiency, its natural history, and outcomes of current treatment practice patterns.
Session topic: 29. Enzymopathies, membranopathies and other anemias
Keyword(s): Hemolytic anemia, Inherited disease, Outcome, Quality of Life
Abstract: PB1966
Type: Publication Only
Background
Pyruvate kinase (PK) deficiency is a rare hereditary glycolytic enzymopathy caused by mutations in the PKLR gene, which lead to reduced red blood cell PK (PK-R) enzyme activity, resulting in defective red blood cell glycolysis and hemolytic anemia. It is the most common cause of glycolytic hemolytic anemia. Over 300 causative PKLR mutations have been identified to date. Patients with PK deficiency may experience symptoms of hemolytic anemia, most commonly fatigue (sometimes extreme), jaundice, dyspnea and weakness. Current treatment is limited to supportive care options. Affected neonates may need phototherapy or exchange transfusions for severe hyperbilirubinemia, while treatment strategies for adults can include red blood cell transfusions, splenectomy/cholecystectomy, and iron chelation, each of which is associated with some risk to the patient. No disease-specific therapy currently exists. The observational PK deficiency Natural History Study (NHS) conducted by Boston Children’s Hospital (ClinicalTrials.gov NCT02053480; N=258) initiated the longitudinal analysis (2-year follow-up) and reporting on PK deficiency-related signs, symptoms and treatment outcomes to better understand the natural history and clinical burden of the disease. The Peak Registry, a global, longitudinal, non-interventional study of PK deficiency, aims to build upon the NHS with additional patients and longer follow-up.
Aims
To report the design of the Peak Registry.
Methods
The Peak Registry is a global, longitudinal, observational registry for adult and pediatric patients with PK deficiency. The 9-year study will enroll approximately 500 patients over 7 years at an estimated 60 study centers in up to 20 countries. All enrolled patients will be followed prospectively for at least 2 years, and up to 9 years. Patients of all ages with a diagnosis of PK deficiency confirmed by genetic testing are eligible to enroll. Each patient or their parent/guardian must be willing and able to give written informed consent and/or assent. Patients who are actively enrolled in any Agios-sponsored clinical trial involving treatment with a PK activator will be excluded. Demographic, clinical, and treatment data, and other data relevant to the management of patients with PK deficiency, will be collected from participating registry physicians via electronic case report forms. The primary objective of the registry is to develop an understanding of the longitudinal clinical implications of PK deficiency, including natural history, treatment and outcomes, variability in clinical care, and disease burden. Secondary objectives include: to understand the prevalence, incidence, and severity of complications associated with PK deficiency; examine phenotype-genotype correlation; evaluate pregnancy outcomes; and provide longitudinal data to assist physicians with the clinical management of individual patients. Site and patient recruitment are ongoing. Study conduct, data analyses and reporting is governed by a steering committee comprised of experts involved in the research, diagnosis, and/or care of patients with PK deficiency in cooperation with the sponsor (Agios Pharmaceuticals, Inc.).
Results
Not yet available.
Conclusion
This non-interventional study aims to extend the work of the NHS with additional patients from an expanded geographic distribution and longer follow-up, to further improve the understanding of the complex clinical burden of PK deficiency, its natural history, and outcomes of current treatment practice patterns.
Session topic: 29. Enzymopathies, membranopathies and other anemias
Keyword(s): Hemolytic anemia, Inherited disease, Outcome, Quality of Life