Rare Daily Staff

The U.S. Food and Drug Administration told Amicus Therapeutics that the company’s clinical package for AT-GAA, its experimental treatment for Pompe disease, is not sufficient to support accelerated approval at this time.

The FDA notified the company following a meeting between the company and regulators to discuss the design of a pivotal study for full approval of AT-GAA and other supplemental studies in Pompe disease patients. The company did say it incorporated feedback from the FDA, along with prior advice from the European Medicines Agency and plans to initiate a pivotal study this year.

Amicus also said it plan to generate data to support additional discussions with the FDA on the potential of an Accelerated Approval pathway for AT-GAA. AT-GAA is a novel treatment that consists of ATB200, a unique recombinant human acid alpha-glucosidase enzyme with optimized carbohydrate structures to enhance uptake, co-administered with AT2221, a pharmacological chaperone that stabilizes the enzyme within the body.

Pompe disease is an inherited lysosomal storage disorder caused by deficiency of the enzyme acid alpha-glucosidase (GAA). Reduced or absent levels of GAA leads to accumulation of glycogen in cells, which is believed to result in the clinical manifestations of Pompe disease. Pompe disease can be debilitating and is characterized by severe muscle weakness that worsens over time. Pompe disease ranges from a rapidly fatal infantile form with significant impacts to heart function to a more slowly progressive, late-onset form primarily affecting skeletal muscle.

AT-GAA is an experimental therapy that consists of ATB200, a unique recombinant human acid alpha-glucosidase enzyme with optimized carbohydrate structures to enhance uptake, co-administered with AT2221, a pharmacological chaperone. In preclinical studies, AT-GAA was associated with increased tissue enzyme levels, reduced glycogen levels in muscle, and improvements in muscle strength. Amicus Therapeutics is currently conducting a global phase 1/2 study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of AT-GAA.

The planned pivotal study, which will compare AT-GAA to the current standard of care, is expected to enroll approximately 100 total Pompe patients. Amicus intends to include both enzyme replacement therapy-switch patients and enzyme replacement therapy treatment-naïve patients in this single pivotal study to support full approval.

The primary endpoint will be 6-minute walk with a primary treatment period of up to 12 months. Patients will be eligible to enroll directly into the pivotal study without participating in the observational study. Patients currently enrolled in study the observational study will be eligible for the pivotal study as well.

Amicus also intends to initiate studies in additional patient populations, including pediatric Pompe patients, in 2019.

“We look forward in the near term to sharing the latest clinical results from the ongoing phase 1/2 study at the World Muscle Society in early October,” said John Crowley, chairman and CEO of Amicus Therapeutics. “Our commitment remains the same as it has always been since we initiated the development of our Pompe cell line—to deliver this potential new therapy to as many people living with Pompe disease as soon as possible.”

September 10, 2018
Photo: John Crowley, Chairman and CEO of Amicus Therapeutics