Substrate Reduction Therapy ABX1100 Named FDA Orphan Drug

ABX1100 led to meaningful reductions in glycogen levels in Pompe mouse model

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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ABX1100, an experimental substrate reduction therapy that Aro Biotherapeutics is developing for Pompe disease, has been granted an orphan drug designation by the U.S. Food and Drug Administration (FDA).

The FDA gives this designation to investigational treatments designed to improve care for rare diseases affecting fewer than 200,000 individuals in the U.S. The status confers certain incentives, including tax credits on clinical testing, waivers of certain fees, and a guarantee of seven years of marketing exclusivity if the therapy is ultimately approved by the FDA.

Clinical trials of ABX1100 are expected to start in mid-2023, according to Aro Biotherapeutics.

“We are pleased to have received this designation and are gratified by the FDA’s recognition of the potential of ABX1100 to improve the lives of patients living with Pompe disease,” Mittie Doyle, MD, Aro’s chief medical officer, said in a press release.

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Pompe disease is caused by mutations in the gene that provides instructions for making acid alpha-glucosidase (GAA), an enzyme that is needed to break down a complex sugar molecule called glycogen. In Pompe, dysfunctional GAA leads to a toxic buildup of glycogen in cells, with muscle cells primarily affected.

The only currently approved treatments for Pompe disease are enzyme replacement therapies, which aim to deliver a functional version of the GAA enzyme to cells.

The goal of ABX1100 is to reduce the production of glycogen in muscle cells, thereby slowing the toxic buildup of this sugar molecule that drives the disease. ABX1100 is designed to reduce the activity of glycogen synthase 1 (Gys1), which helps to synthesize glycogen in muscle cells.

ABX1100 contains a small interfering RNA, or siRNA. When the gene is “read” to make protein, a temporary molecule called messenger RNA, or mRNA, is generated to carry the genetic code to the cell’s protein-making machinery. The siRNA binds to this mRNA, leading to its degradation and ultimately preventing the production of Gys1 protein.

The siRNA in ABX1100 is attached to a centyrin, a modified protein that is designed to bind to receptors on the surface of muscle cells to direct the therapy to these cells. ABX1100 has shown the ability to reduce Gys1 levels and glycogen accumulation in muscle cells of a mouse model of Pompe, with little effect on the liver or kidneys, according to Aro.

“We believe our novel treatment approach has the opportunity to address the great unmet need that exists in Pompe disease, and we are excited to advance ABX1100 to clinical trials in the coming year,” Doyle said.