THANK YOU CDG CARE for having shared this exciting information!

Phase III clinical trial of pediatric subjects with PMM2-CDG begins crossover to open label epalrestat

STURGIS, Mich., March 18, 2024 - Maggie's Pearl, a collaboration between Perlara, Maggie's Cure, and the Mayo Clinic, announced that the Phase III trial of oral epalrestat therapy in pediatric subjects with PMM2-CDG (formerly, Congenital Disorder of Glycosylation Type 1a) has been green-lighted to transition to open label. All study subjects on placebo may transition to open label epalrestat at their 15-month study visit. The principal investigator, study team, participants, and their families remain blinded to original treatment assignments until all subjects reach their 15-month visit.

The crossover recommendation was unanimous among an independent three-member data monitoring committee, comprising two physician scientists with PMM2 expertise and a biostatistician. The DMC concluded the planned interim analysis and determined that the trial can proceed safely. They recommended that each study participant continue with their randomly assigned treatment until the 15-month visit, when they can transition to open label epalrestat.

Administered by the Mayo Clinic, the clinical trial is a prospective, single-center, randomized, double-blind, placebo-controlled study. In December 2021, the Food and Drug Administration notified Maggie's Pearl that the Phase III clinical trial in 40 patients with PMM2-CDG could proceed. The trial recruited 38 study subjects and closed enrollment in November 2023. The first 29 participants will complete their 15-month visits over the next 2-3 months.

PMM2-CDG (phosphomannomutase-2-congenital disorder of glycosylation) is caused by mutations in a gene that supplies the instructions for making the PMM2 enzyme. The enzyme is involved in a process called glycosylation, in which sugar chains are created, altered, and chemically attached to specific proteins to form glycoproteins. Those proteins are key to normal growth and function of tissues and organs. No approved treatment options exist for patients with PMM2-CDG.

"The DMC recommendation to allow study participants to receive epalrestat upon completing 15 months of randomized treatment is very encouraging," said Ethan Perlstein, CEO of Maggie's Pearl. "We can't thank participating families enough. They are medical pioneers and an example for all rare disease communities of what is possible despite the hardships of a placebo-controlled study. We look forward to opening discussions with FDA in the coming months to make epalrestat widely available for all PMM2-CDG families."

The primary study objective is to evaluate the safety and probable benefit of oral epalrestat therapy in pediatric subjects with PMM2-CDG. More at: clinicaltrials.gov/ct2/show/NCT04925960.

About Maggie's Pearl:

Established in August 2020, Maggie's Pearl LLC is a joint venture between Perlara, Maggie's Cure, and the Mayo Clinic to identify potential drug therapies to treat and improve the lives of PMM2-CDG patients. Maggie's Pearl was inspired by Maggie Carmichael, a 10-year-old girl from Sturgis, Michigan, who was diagnosed with PMM2-CDG at eight months of age. At that time, Maggie's parents were told there was no treatment for the rare, and potentially fatal, genetic disease. Globally, roughly 1,000 people are known to have PMM2-CDG. Learn More at www.maggiespearl.com

Phase III clinical trial of pediatric subjects with PMM2-CDG begins crossover to open label epalrestat

STURGIS, Mich., March 18, 2024 - Maggie's Pearl, a collaboration between Perlara, Maggie's Cure, and the Mayo Clinic, announced that the Phase III trial of oral epalrestat therapy in pediatric subjects with PMM2-CDG (formerly, Congenital Disorder of Glycosylation Type 1a) has been green-lighted to transition to open label. All study subjects on placebo may transition to open label epalrestat at their 15-month study visit. The principal investigator, study team, participants, and their families remain blinded to original treatment assignments until all subjects reach their 15-month visit.

The crossover recommendation was unanimous among an independent three-member data monitoring committee, comprising two physician scientists with PMM2 expertise and a biostatistician. The DMC concluded the planned interim analysis and determined that the trial can proceed safely. They recommended that each study participant continue with their randomly assigned treatment until the 15-month visit, when they can transition to open label epalrestat.

Administered by the Mayo Clinic, the clinical trial is a prospective, single-center, randomized, double-blind, placebo-controlled study. In December 2021, the Food and Drug Administration notified Maggie's Pearl that the Phase III clinical trial in 40 patients with PMM2-CDG could proceed. The trial recruited 38 study subjects and closed enrollment in November 2023. The first 29 participants will complete their 15-month visits over the next 2-3 months.

PMM2-CDG (phosphomannomutase-2-congenital disorder of glycosylation) is caused by mutations in a gene that supplies the instructions for making the PMM2 enzyme. The enzyme is involved in a process called glycosylation, in which sugar chains are created, altered, and chemically attached to specific proteins to form glycoproteins. Those proteins are key to normal growth and function of tissues and organs. No approved treatment options exist for patients with PMM2-CDG.

"The DMC recommendation to allow study participants to receive epalrestat upon completing 15 months of randomized treatment is very encouraging," said Ethan Perlstein, CEO of Maggie's Pearl. "We can't thank participating families enough. They are medical pioneers and an example for all rare disease communities of what is possible despite the hardships of a placebo-controlled study. We look forward to opening discussions with FDA in the coming months to make epalrestat widely available for all PMM2-CDG families."

The primary study objective is to evaluate the safety and probable benefit of oral epalrestat therapy in pediatric subjects with PMM2-CDG. More at: clinicaltrials.gov/ct2/show/NCT04925960.

About Maggie's Pearl:

Established in August 2020, Maggie's Pearl LLC is a joint venture between Perlara, Maggie's Cure, and the Mayo Clinic to identify potential drug therapies to treat and improve the lives of PMM2-CDG patients. Maggie's Pearl was inspired by Maggie Carmichael, a 10-year-old girl from Sturgis, Michigan, who was diagnosed with PMM2-CDG at eight months of age. At that time, Maggie's parents were told there was no treatment for the rare, and potentially fatal, genetic disease. Globally, roughly 1,000 people are known to have PMM2-CDG. Learn More at www.maggiespearl.com

THANK YOU CDG CARE for having shared this exciting information!