PMM2-CDG Pediatric Trial Transitions to Open-Label Epalrestat

A pivotal development has been announced in the medical field concerning the treatment of PMM2-CDG, a rare genetic disorder. Maggie's Pearl, a partnership between Perlara, Maggie's Cure, and the Mayo Clinic, has received approval for the Phase III clinical trial of oral epalrestat therapy to move to an open-label phase. This decision allows all pediatric subjects who were previously on a placebo to switch to epalrestat during their 15-month study visit. The study's principal investigator and all involved parties remain unaware of the original treatment assignments until each subject reaches the 15-month mark.

The unanimous recommendation for the transition came from an independent data monitoring committee (DMC) consisting of two physician scientists specialized in PMM2 and a biostatistician. After conducting an interim analysis, the DMC determined that the trial could safely proceed and advised that participants continue their assigned treatments until the 15-month visit, at which point they would switch to open-label epalrestat.

The Mayo Clinic is overseeing the clinical trial, which is designed as a prospective, single-center, randomized, double-blind, placebo-controlled study. The FDA gave the green light for the Phase III trial involving 40 patients with PMM2-CDG in December 2021. The trial enrolled 38 subjects and concluded enrollment in November 2023, with the first 29 participants expected to complete their 15-month visits in the coming months.

PMM2-CDG is caused by mutations in the gene responsible for producing the PMM2 enzyme, which plays a critical role in glycosylation—a process essential for the normal development and functioning of tissues and organs. Currently, there are no approved treatments for PMM2-CDG.

Ethan Perlstein, CEO of Maggie's Pearl, expressed optimism regarding the DMC's recommendation, highlighting the importance of the families' participation in the study. He emphasized their role as medical pioneers and their contribution as an inspiration to rare disease communities. Discussions with the FDA are anticipated to make epalrestat more widely available to PMM2-CDG families.

The primary goal of the study is to assess the safety and potential benefits of oral epalrestat therapy for pediatric patients with PMM2-CDG. More information on the trial can be found at clinicaltrials.gov.

Maggie's Pearl, established in 2020, is a collaborative effort between Perlara, Maggie's Cure, and the Mayo Clinic, with a mission to discover drug therapies for PMM2-CDG patients. The initiative was inspired by Maggie Carmichael, a young girl diagnosed with PMM2-CDG, and aims to improve the lives of those affected by the condition. It is estimated that approximately 1,000 individuals worldwide are living with PMM2-CDG.