The Future of Celiac Disease Management

 Drug-Based Treatment for Celiac Disease

Living with celiac disease can be a frustrating and often isolating experience. While avoiding gluten is the only current treatment option, it doesn’t always eliminate all symptoms and can be difficult to maintain.

Imagine a future where people with celiac disease can manage their symptoms with targeted drugs that reduce inflammation and improve their quality of life. The drug candidates we’ll discuss in this article offer a potential path to this future, with each one targeting a different aspect of the disease.

 The Need for a Drug-Based Treatment

The investigational drugs outlined here are intended to act as adjunctive therapies to further protect against accidental exposures or help enable the safe consumption of small amounts of gluten. However, they are not anticipated to replace the need for dietary modifications altogether.

Patients should continue following nutritional advice from their healthcare providers even if new pharmacologic options become available. While this wave of therapeutic development holds promises for better treating celiac disease, it is important to note that adherence to a strict gluten-free diet is still considered essential for controlling symptoms and intestinal damage from the condition.

Combining the proven effectiveness of gluten avoidance with the potential protection from emerging drugs could provide reliable, multifaceted disease control to meaningfully improve the quality of life for those living with this challenging autoimmune disorder.

 A list of drugs in development

KAN-101 also known as Larazotide Acetat

Company: Anokion

Mechanism: KAN-101 (Larazotide acetate) is a tight junction regulator peptide designed to help maintain intestinal integrity and reduce intestinal permeability.

Stage of development: 2 clinical trials

Trial Phase: Currently in Phase 2 efficacy trials for treating celiac disease.

Role in Management of Celiac Disease: KAN-101 is intended to be used as an adjunct therapy to a gluten-free diet for celiac disease. By helping maintain tight junctions in the intestines, it can reduce exposure to gluten and alleviate immune-mediated GI damage and symptoms in celiac patients.

Additional Info: KAN-101 was granted Fast Track Designation from the FDA for the treatment of celiac disease. It has an Orphan Drug Designation from the European Medicines Agency. If approved, KAN-101 would be the first FDA-approved adjunctive therapy to a gluten-free diet for celiac disease.

DAN-101

Develop company: ImmusanT, Inc

Mechanism of action: Designed to block a specific enzyme involved in gluten, potentially preventing immune activation in celiac patients.

Development phase: Pre-clinical stage.

Additional information: Early studies suggest promising results in blocking gluten-induced immune responses in celiac disease models.

Administration method: Not publicly available yet.

CALY-002

Company: Calypso Biotech

Mechanism of Action: Immune tolerance – induces immune tolerance to gluten. Targets a molecule involved in immune activation triggered by gluten, potentially suppressing the inflammatory response in celiac disease.

Phase of Development:  CALY-002 has completed the dosing of the first Celiac Disease patient in its Phase 1 clinical trial. This trial includes a single ascending dose in healthy volunteers (which is now completed) as well as ascending dosing in cohorts of patients with Celiac Disease and Eosinophilic Esophagitis, both of which are conditions with significant unmet medical needs and where IL-15 plays a critical role.

Stage of Development: Phase 2a.  Latest Trial Results: In a Phase 2a trial, Caly-002 showed statistically significant reductions in celiac disease biomarkers compared to placebo. This suggests it may help induce tolerance and reduce immune reaction to gluten.

 Administration: Subcutaneous injection.

Additional Information: CALY-002 is positioned as a potentially paradigm-changing treatment for several gastrointestinal indications, including those with no currently approved treatment, as well as other large immune pathologies​​.

PRG-015

Developer: Prometheus Biosciences, Inc

Mechanism of action: Inflammation modulator – acts to dampen inflammatory immune response triggered by exposure to low doses of gluten. Targets a molecule involved in immune activation triggered by gluten, potentially suppressing the inflammatory response in celiac disease.

Stage of development: pre-clinical stage

Latest Trial Results: In preclinical studies, PRG-015 suppressed immune system activation and inflammation in intestinal tissue culture samples from patients with celiac disease who were exposed to gluten.

Additional information: Early research suggests potential for preventing gluten-induced inflammation in celiac disease models.

Administration method: Not publicly available yet.

Next Steps: Further preclinical safety and mechanism of action evaluations before moving into Phase 1 clinical trials.

AVL-176

Developer: Avalia Biotherapeutics, Inc

Mechanism of Action: A modified enzyme that breaks down gluten peptides before they reach the small intestine, potentially preventing immune activation in celiac patients. Oral antibody – binds to deamidated gliadin peptides (DGPs) in the intestine to block immune activation.

Stage of Development: Phase 1 clinical trial ongoing

Latest Trial Results: A Phase 1 study demonstrated AVL-176 was safe and well-tolerated. Further trials are planned to evaluate efficacy. Initial studies showed promising safety and tolerability in healthy volunteers. Further research is needed to assess its efficacy in celiac disease patients.

Role in Management: Being developed as an oral medication to use in conjunction with a gluten-free diet to help neutralize traces of gluten.

Administration method: Not publicly available yet

 AMG-510

Developer: Amgen Inc.

Mechanism of Action: Anti-transglutaminase antibody binds to and inhibits tissue transglutaminase (tTG), a key enzyme that modifies gluten peptides triggering an immune reaction. Targets a molecule involved in T cell activation, potentially preventing the immune response triggered by gluten in celiac disease.

Stage of Development: Pre-clinical

Latest Results: Has shown the ability to block tTG enzyme and subsequent inflammatory effects in vitro. Further preclinical development is planned.

Administration method: Not publicly available yet.

TAK-883

Developer: Takeda Pharmaceutical Company Limited

Mechanism of Action: JAK inhibitor – blocks JAK/STAT inflammatory signaling pathway involved in immune activation in celiac disease. Binds to a protein involved in gluten absorption, potentially preventing its entry into the gut lining, and triggering an immune response in celiac patients.

Stage of Development: Phase 1 clinical trial ongoing

Latest Results: Early-stage safety trials are underway.

Additional information: Initial studies show promising safety and tolerability in healthy volunteers. Further research is needed to assess its efficacy in celiac disease patients.

Next Steps: Further clinical studies to evaluate efficacy.

Administration method: Not publicly available yet.

While this wave of therapeutic development holds promising possibilities for treating celiac disease, it is important to note that healthcare professionals still consider adherence to a strict gluten-free diet essential for controlling symptoms and intestinal damage from the condition.

As further research and development progress, individuals with celiac disease may have new options for managing their condition and improving their quality of life.

Of note: Due to the fluidity of drugs in the development stages, it is not unusual for information to change.