"This Phase 2 study has shown that PEG-PAL appears to control Phe levels independent of the Phe-restricted diet and can produce a sustained response," stated Dr. Nicola Longo, Professor of Pediatrics and Adjunct Professor of Pathology at the University of Utah and Clinical Investigator in the PEG-PAL Phase 2 trial. "Most adult PKU patients are unable to adhere to a Phe-restricted diet and as a result, they can suffer from decreased mental, social and behavioral functioning. PEG-PAL may offer these patients the possibility of freedom from the Phe-restricted diet."
During the Phase 2 program, PEG-PAL was generally well-tolerated. Only two patients discontinued PEG-PAL due to adverse reactions, neither of which was reported to be severe. Twelve other patients discontinued participation in the program primarily due to logistical reasons. Forty-two patients remain on PEG-PAL in the open-label extension study. Of these, 25 patients have been treated longer than one year, including 15 patients who have been treated longer than two years. In total, there have been more than 800 patient months of treatment with PEG-PAL. The principal adverse reaction believed to be related to PEG-PAL occurs during initial dosing of the drug and appears to be hypersensitivity-type reactions consisting of injection-site reaction, disseminated skin reaction or joint pain. While these reactions were observed in nearly all PEG-PAL patients during their initial introduction to the drug, the reactions are generally mild to moderate and self-limited. Importantly, patients who have these types of reactions have all been successfully re-treated with PEG-PAL. During long-term exposure to PEG-PAL, injection-site and hypersensitivity reaction rates decreased dramatically and there was no laboratory evidence of liver or kidney injury.
Most recently, in the Phase 2 Part D study, BioMarin has investigated an accelerated personalized dosing regimen for introduction of PEG-PAL to get patients to active doses as quickly as possible while minimizing hypersensitivity-type reactions. Patients started with a fixed induction dose of 2.5 mg for four weeks. The dose escalated to 75 mg/week based on individual patient tolerability, at which point patients switched to a daily maintenance dose. In this part of the Phase 2 program, the earliest a patient was able to reach the maintenance dose was nine weeks, and half were able to achieve efficacy at or prior to reaching maintenance dosing in less than 13 weeks.