There are currently no treatments available for celiac disease beyond a gluten-free diet. Several late-phase companies aim to change the paradigm and deliver hope and progress soon.
Despite the failure in recent years of celiac disease candidates such as 9 Meters’ larazotide and Amgen’s AMG 714, multiple companies are forging ahead with development of therapies for the autoimmune disease, with promising results.
Celiac disease is a chronic autoimmune disorder that damages the small intestine and prevents the body from absorbing nutrients from food. Flare-ups arise in response to contact with gluten. This disease affects 3 million Americans, and the only recommended intervention is a gluten-free diet. As patients continue to be exposed to gluten chronically, even low levels of the protein can lead to further health complications such as lymphoma, bowel cancer, osteoporosis, anemia or malnutrition.
Several companies are working on late-stage investigational treatments to treat celiac disease via a variety of therapeutic approaches. If ultimately approved, these treatments should change care for the disease profoundly by removing the burdensome need for total gluten avoidance.
The frontrunner, Entero Therapeutics, is researching latiglutenase, an enzyme that breaks down gluten in the stomach. Also known as IMGX003, latiglutenase is an orally administered mixture of two gluten-specific recombinant proteases that degrades gluten proteins into smaller pieces. Phase III celiac disease trials for latiglutenase are slated to start early this year.
Entero published results in August 2022 from a placebo-controlled Phase II trial of latiglutenase. In the 6-week gluten challenge after randomization, the mean change in the ratio of villus height to crypt depth was used as the primary endpoint, and latiglutenase was proven superior to placebo in reducing gluten-associated small intestine mucosal damage.
Meanwhile, Anokion is actively enrolling patients for its Phase II SynCeD trial of KAN-101, a synthetic gluten antigen delivered to the liver and immune cells with a liver-targeting glycosylation signature.
In the Phase I ACeD trial, patients were divided into two study parts. Part A was an open-label, single ascending dose study in which intravenous KAN-101 was administered using sentinel dosing. Meanwhile, Part B was a randomized, placebo-controlled multiple ascending dose study. While commonly observed adverse events as of June 2023 included nausea, diarrhea, abdominal pain and vomiting, these effects were attributed to disease symptoms caused by gluten.
In May 2024, Anokion reported results from the Phase Ib/II ACeD-it trials, revealing that KAN-101 was safe and remained well-tolerated at higher dose levels up to 3 mg/kg. In addition, functional tolerance to gluten was observed.
Elsewhere, Sanofi is enrolling Phase II trials of amlitelimab, an OX40L subcutaneous monoclonal antibody. OX40L is a ligand found on some immune cells, and binding it limits their activity. In the trials, Sanofi will assess patients who are not responsive to celiac disease interventions and will differentiate between different variables by making use of experimental and placebo trial arms and by comparing consistently gluten-free diets to simulated inadvertent gluten exposure. Alternatively known as SAR445229 or KY1005, amlitelimab is also undergoing research for other indications such as atopic dermatitis, systemic sclerosis, alopecia areata, hidradenitis suppurativa and asthma.
Finally, Takeda is developing three investigational agents to treat celiac disease. TAK-101 is a tolerizing immune-modifying nanoparticle intravenous injection and zamaglutenase (also known as TAK-062 or Kuma062) is an orally administered glutenase enzyme, making both agents biologics. TAK-227 (a.k.a. ZED-1227), an orally administered transglutaminase 2 inhibitor, is by contrast a small molecule. While Takeda is currently enrolling for Phase II TAK-101 trials, its Phase II zamaglutenase trials were completed as of November 2024. TAK-227’s Phase I proof-of-concept data, released in 2021, showed that TAK-227 attenuated gluten-induced duodenal mucosal damage in patients with celiac disease.
In conclusion, several investigational treatments are vying to treat celiac disease. Despite earlier setbacks, patients should look forward to new treatments coming within the next 3–5 years at the earliest in this space.
