pegvaliase

Pegvaliase is a recombinant phenylalanine ammonia lyase (PAL) enzyme derived from Anabaena variabilis that converts phenylalanine to ammonia and trans-cinnamic acid . Both the U.S. Food and Drug Administration and European Medicines Agency approved pegvaliase-pqpz in May 2018 for the treatment of adult patients with phenylketonuria (PKU). Phenylketonuria is a rare autosomal recessive disorder that is characterized by deficiency of the enzyme phenylalanine hydroxylase (PAH) and affects about 1 in 10,000 to 15,000 people in the United States . PAH deficiency and inability to break down an amino acid phenylalanine (Phe) leads to elevated blood phenylalanine concentrations and accumulation of neurotoxic Phe in the brain, causing chronic intellectual, neurodevelopmental and psychiatric disabilities if untreated . Individuals with PKU also need to be under a strictly restricted diet as Phe is present in foods and products with high-intensity sweeteners . The primary goal of lifelong treatment of PKU, as recommended by the American College of Medical Genetics and Genomics (ACMG) guidelines, is to maintain blood Phe concentration in the range of 120 µmol/L to 3690 µmol/L .

Pegvaliase-pqpz, or PEGylated pegvaliase, is used as a novel enzyme substitution therapy and is marketed as Palynziq for subcutaneous injection. Pegvaliase-pqpz is a homotetrameric protein composed of recombinant phenylalanine ammonia lyase (rAvPAL) conjugated to N-hydroxysuccinimide (NHS)-methoxypolyethylene glycol (PEG). It is advantageous over currently available management therapies for PKU, such as Sapropterin, that are ineffective to many patients due to long-term adherence issues or inadequate Phe-lowering effects . The presence of a PEG moiety in pegvaliase-pqpz allows a reduced immune response and improved pharmacodynamic stability .

用于尽管接受先前可用的治疗方案但仍无法充分控制血液苯丙氨酸（Phe）水平（血液Phe水平＞600微摩尔/升）的16岁及以上苯丙酮尿症（罕见病：PKU）患者，降低其血液Phe水平 。