First clinical site in China opens for Phase 2 trial of AL01211
Study to evaluate treatment's safety, efficacy in men with classic Fabry
The trial is actively screening and enrolling patients across six sites in China, including Shanghai’s Ruijin Hospital. Five other sites are expected to open by the end of the year.
The study will evaluate the therapy’s safety, efficacy, and pharmacological properties in men with classic Fabry disease not previously treated with other therapies for the disease. The company expects to present top-line data by the second half of 2024.
“The opening of our first clinical trial site in China demonstrates our ongoing commitment to Fabry Disease and is an important step in our efforts to provide these patients with a convenient, oral, therapeutic option,” Pedro Huertas, MD, PhD, chief medical officer of AceLink Therapeutics, said in a press release.
Fabry disease is caused by mutations in the GLA gene, which provides instructions to produce the alpha-galactosidase A (Gal A) enzyme. The enzyme is responsible for breaking down fatty molecules, mainly globotriaosylceramide (Gb3 or Gl-3).
These mutations result in reduced or absent Gal A enzyme activity, leading to the toxic accumulation of these fatty molecules and inflammation, and ultimately leading to organ damage.
“The symptoms of Fabry disease are extremely burdensome, have a negative impact on the quality of life of both patients and their families,” said Nan Chen, principal investigator for the study and professor of the Department of Nephrology at Ruijin Hospital.
Standard enzyme replacement therapies work by providing a functional version of the Gal A enzyme, partially compensating for the inability to break down Gb3.
Substrate reduction therapy blocks function of glucosylceramide synthase
AL01211, also referred to as AL1211, is a substrate reduction therapy, meaning it acts by preventing the production of fatty molecules like Gb3.
Specifically, it blocks the function of the glucosylceramide synthase (GCS), an enzyme that promotes the production of glycosphingolipids, a group of biologically active fatty molecules that includes Gb3. This prevents Gb3 buildup, therefore improving organ function and slowing disease progression.
The treatment offers the advantage of being an oral small molecule, as an alternative to intravenous (IV, into the vein) infusions required for enzyme replacement therapy.
“Even with advancements made in enzyme replacement therapies, the potential of immune reaction and the reoccurring need for IV infusion highlights a significant unmet need for an effective oral therapy. With this in mind, we are truly excited about our participation in this trial, as we strive to improve the daily lives of patients with Fabry disease,” Chen said.
AL01211 is also unable to cross the blood-brain barrier, a membrane that protects the brain and spinal cord (collectively known as the central nervous system, CNS) from the external environment, meaning it will not enter the CNS. This maximizes the treatment effect on intended organs and reduces potential side effects on the CNS.
AL01211 completed Phase 1 clinical trials in Australia (NCT04908462) and China (ChiCTR2200061431), which showed it was generally safe and well tolerated without any serious adverse effects, according to the company.
Moreover, the expected levels of blood glycosphingolipids were reduced with increasing doses of the treatment, particularly glucosylceramide, a marker of GCS inhibition, and Gb3.
The therapy was granted orphan drug designation by the FDA in 2022, a designation given to experimental therapies that hold promise for enhancing care for rare diseases.