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Early-stage data support KAN-101, a liver-targeting drug that's vying to become the first treatment approved to treat celiac disease.
A liver-targeting investigative drug designed to induce immune tolerance to wheat gluten has shown dose regimen safety and pharmacokinetic potential for the treatment of celiac disease, an autoimmune disease characterized by inflammatory reaction to gluten in the small intestines.
KAN-101, a glycosylation signature conjugated to deanimated gliadin peptide under development by Anokion, was associated with acceptable safety, no dose-limiting toxicities and a rapid systemic clearance in the first-in-human phase 1 ACeD trial assessing its benefit for celiac disease.
“We’re excited to share these new data from our phase 1 trial, which further establish that KAN-101 induces immune tolerance to gluten in people with celiac disease,” Deborah Geraghty, PhD, Anokion chief executive officer, said in a statement. “As a highly burdensome condition with no disease-modifying therapies available today, KAN-101 could be a game changer for patients, with durable treatment effects observed following administration.”
An Anokion-supported team led by Kristie M. Grebe, PhD, sought to assess the safety and pharmacokinetics of KAN-101 in patients with celiac disease—a condition that investigators noted requires a gluten-free diet from affected patients, and is currently without a treatment option approved by the US Food and Drug Administration (FDA).
Grebe and colleagues enrolled 41 adult patients aged 18 – 70 years old with biopsy-confirmed celiac disease from 10 clinical research centers and hospitals in the US. All enrolled patients featured the HLA-DQ2.5 genotype, the primary gene for celiac disease. The team sought a primary endpoint of plasma concentrations and pharmacokinetic parameters of KAN-101 after single and multiple doses among patients who received ≥1 dose.
Fourteen patients were initiated to an open-label, single-ascending dose assessment of intravenously (IV) administered KAN-101; they received sentinel dosing of regimen cohorts of 0.15 mg/kg (n = 4); 0.3 mg/kg (n = 3); 0.6 mg/kg (n = 3); 1.2 mg/kg (n = 3); and 1.5 mg/kg (n = 1).
After a safety review of the lowest dose regimen, investigators randomly assigned the other 27 patients 5:1 to a regimen of 3 KAN-101 doses of 0.15 mg/kg (n = 6), 0.3 mg/kg (n = 7), 0.6 mg/kg (n = 8), or placebo (n = 6), followed by 3-day oral gluten challenges of 9 g daily 1 week after completion of treatment.
Investigators observed treatment-related adverse events (AEs) in 11 (79%) of the patients initiated in the open-label safety assessment, and 18 (67%) of the patients in the randomized assessment; in the latter cohort, 16 patients had received KAN-101.
AEs were mild to moderate in severity, with the most common events being nausea, diarrhea, abdominal pain and vomiting—symptoms consistent with celiac disease or gluten ingestion. Investigators observed no serious AEs, dose-limiting toxicities, nor deaths among patients.
The team’s pharmacokinetic analyses showed KAN-101 cleared from systemic circulation in treated patients within approximately 6 hours, with a geometric mean half-life of 3.72 – 31.72 minutes. Half-life did not accumulate with repeated dosing.
With the phase 1 trial complete, investigators stated their intention to further analyze KAN-101’s efficacy and safety in human patients—featuring biomarker responses from a gluten challenge—at doses of ≥0.6 mg/kg in patients with celiac disease.
“KAN-101 has an acceptable safety profile in patients with celiac disease with no dose-limiting toxicities and no maximum tolerated dose was observed,” investigators concluded. “Rapid systemic clearance of KAN-101 was observed and no accumulation on repeated dosing.”