Preformulation Studies with Phenylalanine Ammonia Lyase: Essential Prelude to a Microcapsule Formulation for the Management of Phenylketonuria

Pharmacodynamics, safety, tolerability and pharmacokinetics of a single oral dose of an engineered phenylalanine ammonia-lyase in patients with phenylketonuria

“…This pattern is indicative that CDX-6114 has a short half-life, which may be due to the liquid formulation being applied in the study or the inability to withstand the lower pH encountered in the human stomach compared with the animal models used in earlier studies [ 25 ]. PAL sensitivity to low pH is well described [ 26 ], and multiple attempts have been made to protect it to optimise its function using proton pump inhibitors (PPIs) [ 27 ]. Unfortunately, the long-term use of PPIs is an increasing concern [ 28 ].…”