MZE001 Wins FDA Orphan Drug Status for Pompe Disease

MZE001 could be monotherapy for late-onset patients, complement to enzyme replacement therapies: Maze CEO

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

Share this article:

Share article via email
A young man shouts into a megaphone.

The U.S. Food and Drug Administration (FDA) has granted orphan drug designation to MZE001, Maze Therapeutics‘ investigational oral treatment for Pompe disease.

“Pompe disease is a serious and often fatal disorder, and MZE001 has the potential to offer patients an oral, disease-modifying option that improves clinical outcomes and quality of life,”  Jason Coloma, PhD, Maze CEO, said in a company press release. “We are pleased to have received this designation from the FDA for MZE001, which underscores the need for new, innovative treatments for Pompe disease.”

The orphan drug designation is intended to speed the development of potential treatments for rare diseases, which are defined as those affecting fewer than 200,000 people in the U.S. It provides a number of financial incentives and regulatory support as well as seven years of marketing exclusivity if the therapy is ultimately granted regulatory approval.

Recommended Reading
Illustration shows a medicine bottle labeled

First Healthy Volunteers Dosed in Trial of Oral Therapy MZE001

Pompe disease is caused by mutations in the gene that provides the instructions to make acid alpha-glucosidase (GAA), an enzyme needed to break down a large sugar molecule called glycogen.

As a result of the mutations, not enough functional GAA is produced, causing glycogen to build up to toxic levels in several tissues, especially the muscles.

Enzyme replacement therapy (ERT) is the standard treatment for Pompe. It works by delivering a lab-made version of GAA to patients, helping to lower glycogen levels and ease symptoms. However, some patients using ERT still show signs of disease progression.

MZE001 is an oral small molecule that acts as a substrate reduction therapy. Instead of increasing the amount of enzyme needed to break down excess glycogen, the therapy aims to lower glycogen production at its source.

It works by suppressing the activity of muscle glycogen synthase (GYS1), the enzyme that produces glycogen in muscle cells. This is expected to prevent its toxic accumulation in muscles, slowing Pompe progression.

MZE001 was developed using the company’s Compass platform, which combines human genetic data, genomic tools, and data science technology to identify promising therapeutics targets. With it, Maze has been able to overcome certain challenges in targeting GYS1, including its structural complexity and the uncertainty of long-term glycogen reduction.

“MZE001 is a novel mechanism we believe could be beneficial both as a monotherapy for late-onset patients as well as complement to enzyme replacement therapies across the disease spectrum,” Coloma said.

In preclinical studies, MZE001 was shown to potently and selectively inhibit GYS1 in lab-grown cells from healthy people and Pompe patients, as well as in mouse and canine models of the disease.

In animal models, it also reduced glycogen accumulation and markers of muscle damage. These effects were even greater when MZE001 was combined with ERT — the combo treatment resulted in normal glycogen levels and restored cellular health.

MZE001 also was well tolerated, with no toxicity observed across multiple species.

An ongoing Phase 1 trial (NCT05249621) is evaluating the safety and effectiveness of single and multiple ascending doses of MZE001 in up to 80 healthy adult volunteers.

It’s also assessing the therapy’s pharmacokinetics — its movement into, through, and out of the body — and pharmacodynamics, or its effects on the body. The effects of food on these measurements will also be assessed.

“Our Phase 1 trial in healthy volunteers is advancing well, and we look forward to sharing data generated from the study later this year,” Coloma said.

The trial is expected to conclude in December and Maze has announced plans to initiate a Phase 2 trial in Pompe patients during the first half of 2023.