Tag Archives: latiglutenase

Safety Net for Celiac Disease?

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JA Murray, JA Syage et al.Gastroenterol 2022; 163: 1510-1521. Open access! Latiglutenase Protects the Mucosa and Attenuates Symptom Severity in Patients With Celiac Disease Exposed to a Gluten Challenge

Background: Latiglutenase (IMGX003) is an investigational dual-enzyme drug candidate that acts to degrade gluten in vivo when consumed with a meal. The authors note that “despite strict adherence to a GFD, about half of CD patients show evidence of persistent small intestinal mucosal injury (Marsh grades II–III);’ thus, there is a need to improve treatment with other measures in addition to diet.

Methods: 43 patients (IMGX003, n = 21; placebo, n = 22) completed this double blind and placebo controlled study which assessed the efficacy and safety of a 1200-mg dose of IMGX003 in patients with celiac disease (CD) exposed to 2 g of gluten per day for 6 weeks study

Key findings:

  • In IMGX003-treated patients, there was less damage to mucosa. The mean change in the ratio of villus height to crypt depth (primary endpoint) for IMGX003 vs placebo was –0.04 vs –0.35 (P = .057). The mean change in the density of intraepithelial lymphocytes (secondary endpoint) for IMGX003 vs placebo was 9.8 vs 24.8 cells/mm epithelium (P = .018). 
  • Measurements of gluten-immunogenic peptides (GIP) in urine indicated 95% gluten degradation in the stomach by latiglutenase.

The 2 g dose per meal of gluten allowed used in the study, “would likely substantially exceed that accidently occurring while on a GFD, 4 supporting such an approach for management for gluten-triggered symptoms in treated patients.”

Graphical abstract:

In both the placebo and IMGX003 groups, there was an increases in symptoms, but this was blunted in the treated group–Figure 2:

My take: This study shows the potential for latiglutenase to act as a ‘safety net’ to protect from CD from accidental gluten exposure. The findings reinforce the idea that this agent is not likely to be effective in the absence of gluten restriction. As an aside, I would be interested in finding out whether patients with presumed non-celiac gluten sensitivity would improve on this therapy.

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Latiglutenase Not Effective for Celiac Disease, Plus One

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A recent study (JA Murray et al. Gastroenterol 2017; 152: 787-98) examined the effectiveness of  latiglutenase for celiac disease.  Latiglutenase (aka ALV003) is an oral medicine which is a mixture of two recombinant gluten-targeting proteases.

The concept of latigluenase is that a medicine that degrades the gluten protein could obviate the need for a gluten free diet.  Unfortunately, in this study with 494 patients with celiac disease for at least 1 year, the medicine at various doses for 12 to 24 weeks was ineffective. There was no difference between the medicine and placebo with regard to villous height:crypt depth ratio, number of intraepithelial lymphocytes or serologic markers of celiac disease.  Symptom scores increased in both the active treatment group and the placebo group.  While this was a negative study, the authors did note some effect on symptom domains on higher dosing regimens. “This observation suggests that treatment with latiglutenase may affect symptoms before showing clinically meaningful effects on serologic and histologic end points.

A second study (RS Choung et al. Gastroenterol 2017; 152: 830-9) examined prevalence and morbidity of undiagnosed celiac disease in Olmstead County. After excluding patients with celiac disease, sera from 30,425 adults and 830 children were tested for tissue transglutaminase IgA antibody (tTG)  and endomysial antibody (EMA).  Case definition: patients were considered to have celiac serologically if tTG titer was 2.0 U/mL or greater with a positive EMA. The prevalence of celiac disease was 1.1% in adults and 1.0% in children. The majority of patients with celiac disease (>80%) have not received the diagnosis.  By comparing those with positive celiac serology to matched controls (2 controls for each positive), the authors determined that undiagnosed celiac disease was associated with increased rates of hypothyroidism (OR 2.2) but no other significant morbidities.  Median followup period was 6.3 years.

My take: A promising new therapy for celiac disease, latiglutenase, looks like it will not be effective and there are a lot of individuals with celiac disease who are unaware of their diagnosis.

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Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

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