Authors :
Presenting Author: Phillip Pearl, MD – Boston Children's Hospital & Harvard Medical School
Laura Cole, PhD – Medicure
Nancy Stewart, PhD – Medicure
Sandra Reis, PhD – Medicure
Muhammad Zafar, MD – Duke University School of Medicine
Monisha Goyal, MD – UAB
Courtney Wusthoff, MD – Stanford Univ
Matthew Ginsberg, MD – Akron Children's Hospital
Kate Riney, MB, BCh, BAO, PhD – Neurosciences Unit, Queensland Children’s Hospital, South Brisbane, QLD, Australia; University of Queensland, Brisbane, QLD, Australia
Johan Van Hove, MD – Colorado Children's
Heidi Peters, MD, PhD – Royal Children's Hospital
Neil Owens, PhD – Medicure
Albert Friesen, PhD – Medicure
Rationale:
PNPO deficiency, or pyridoxal 5’-phosphate (P5P) dependent epilepsy, is currently treated with various and artisanal dietary supplement forms of P5P. This trial evaluates the efficacy of MC-1 (pharmaceutical grade formulation of P5P) for maintenance treatment of patients with confirmed PNPO deficiency. Secondary objectives are to evaluate medication safety and document the disorder’s natural history.
Methods:
In this phase 3, open label, multi-center prospective trial, confirmed PNPO patients (aged ≥2 years), typically controlled with oral P5P, are treated with pharmaceutical grade 50 mg MC-1 tablets for 52 weeks. Outcomes include incidence of death compared to an external untreated disease control cohort derived from literature and frequency of seizures compared to a period without any P5P treatment.Results:
Six patients (2 male, 4 female) have been enrolled in the study as of the date of this abstract. Of these, one patient completed the one-year trial, while another is currently in the seventh month of treatment. Baseline treatment regimens ranged between 22 mg/kg/day to 58 mg/kg/day, using both crushed and intact tablets. Baseline steady state P5P levels were also variable between subjects, ranging from 4.84 ng/mL to 136 ng/mL. Once the transition period from dietary supplements to study drug dosing is completed, the intervention is well tolerated with no exacerbation of seizures, or serious adverse events attributable to the P5P intervention.
Conclusions:
The first trial of a pharmaceutical grade of the vitamer P5P in PNPO dependent epilepsy is in progress and initial results demonstrate good efficacy, safety, and tolerability. Funding: Medicure Inc. is the trial sponsor.