ABX1100 treatment for Pompe disease now in 1st trial in people
Safety of substrate reduction therapy to be tested in healthy volunteers
The first healthy volunteer has been enrolled in a Phase 1 study testing ABX1100 — a novel substrate reduction therapy from Aro Biotherapeutics — as a treatment for Pompe disease.
This will be the first-in-human trial for the experimental therapy, meaning it’s the first time ABX1100 has been tested in people.
“We are thrilled to advance ABX1100 into the clinic,” Mittie Doyle, MD, Aro’s chief medical officer, said in a company press release.
The trial, being run in Canada, will test single doses of ABX1100 or a placebo in healthy volunteers, with a goal of assessing its safety and tolerability in people. The study also will evaluate the treatment’s pharmacokinetic and pharmacodynamic properties — that is, how it moves through and out of the body, and how it affects the body in turn — as well as biomarker data to assess whether ABX1100 appears to be working as designed.
“Initiating our Phase 1 study represents a critical step toward our goal of transforming the lives of patients with Pompe Disease,” Doyle said.
1st person now enrolled in trial of Pompe disease treatment candidate
Pompe disease is caused by mutations that disrupt the activity or production of the enzyme acid alpha-glucosidase, known as GAA. This enzyme normally is responsible for breaking down the complex sugar molecule glycogen. In Pompe, glycogen builds up to toxic levels inside cells, especially muscle cells, ultimately driving disease symptoms.
The only available treatments for Pompe disease to date are enzyme replacement therapies or the combination treatment Pombiliti + Opfolda. These therapies aim to deliver a working version of the GAA enzyme to the body’s cells.
ABX1100, meanwhile, is designed for a different treatment strategy called substrate reduction.
The idea behind substrate reduction therapy is to block the production of glycogen, thus helping to prevent the toxic buildup of this molecule. ABX1100 uses a molecule called a small interfering RNA, or siRNA, to decrease the levels and activity of glycogen synthase 1 (Gys1), an enzyme that’s responsible for making glycogen in cells.
Aro developed a proprietary platform to deliver this siRNA to muscle cells.
We are proud of the work our team has accomplished from discovery through initial clinical testing of ABX1100 and are motivated by our shared goal of bringing a new therapy with unsurpassed efficacy, safety and durability to patients with Pompe disease.
“Our Phase 1 study of ABX1100 provides an excellent opportunity to demonstrate the potential of our Centyrin-siRNA platform, for targeting siRNAs to tissues beyond the liver,” said Susan Dillon, PhD, president and CEO of Aro.
“We are proud of the work our team has accomplished from discovery through initial clinical testing of ABX1100 and are motivated by our shared goal of bringing a new therapy with unsurpassed efficacy, safety and durability to patients with Pompe disease,” Dillon said.
The U.S. Food and Drug Administration last year granted ABX1100 both orphan drug and rare pediatric disease designations, which are designed to incentivize the development of therapies for rare disorders where there might not otherwise be an economic incentive to develop treatments.
About the Author
