Alv003

BACKGROUND & AIMS: Celiac disease (CD) is a chronic inflammatory disease of the small intestine induced and maintained by gluten ingestion in susceptible individuals. Current treatment consists of strict adherence to a lifelong gluten-free diet (GFD) which is considered safe and effective in the large majority of patients. However, since adherence to a GFD is difficult and has a negative impact on quality of life, an increasing interest in other treatment options has emerged. Moreover, in some individuals a GFD is not sufficiently effective, necessitating alternative treatments...

BACKGROUND & AIMS: Villus height to crypt depth ratio (Vh:Cd) and intraepithelial lymphocytes (IEL) are key measures of histology of the small intestine in celiac disease (CeD). While the field of CeD has advanced, there remains no broadly accepted measure of mucosal injury. We assessed whether a composite Vh:Cd and IEL scale (named VCIEL) can improve accuracy and statistical precision for assessing histology, compared to individual measures. METHODS: The formulation of the VCIEL composite histologic scale was based on combining the Vh:Cd and IEL measurements for individual patients with equal weighting, by converting each scale to a fraction of their standard deviation and summing the results...

Celiac Disease (CeD) is estimated to currently affect 2 million Americans in the United States. This autoimmune disorder occurs when the consumption of gluten-based products leads to an inflammatory response in the small intestine. Over time, this inflammatory response permanently damages the villi in the small intestine. Celiac disease patients generally present with fatigue, diarrhea, and weight loss due to the disease. The current gold standard for diagnosing CeD is the endoscopy with duodenal biopsy indicating villous atrophy and crypt hyperplasia...

Background: Celiac disease (CD) is a widespread autoimmune disease triggered by dietary gluten that can lead to severe gastrointestinal symptoms. Because there is no available treatment other than a lifelong gluten-free diet, many patients continue to experience chronic symptoms. Aim: In this analysis we report on the efficacy of latiglutenase, an orally administered enzyme treatment, for improving multiple gluten-induced symptoms and consequent quality of life (QOL) due to inadvertent gluten consumption...

This is a selective review of the literature concerning the methods of celiac disease treatment, which can be an alternative to a gluten-free diet. The most advanced studies are devoted to the larazotide acetate (AT-1001, human zonulin inhibitor) and prolyl-endopeptidases degrading toxic gluten peptides (ALV003, AN-PEP). It is estimated that they will be registered within a few years. They will not become an alternative to the gluten-free diet but rather a supplement to it, which will enable patients to ease the nutritional restrictions...

Currently, the only effective treatment for celiac disease is a strict lifelong gluten-free diet. However, gluten-free dieting is restrictive, difficult to maintain and nutritionally less than optimal. The improved knowledge on celiac disease pathogenesis has enabled researchers to suggest alternative strategies to treat the disorder. The drug development poses a challenge as any novel drug for celiac disease should be simultaneously effective and as safe as the gluten-free diet. The rationale behind enzyme supplementation therapy as a future treatment option for celiac patients lies in the fact that gluten is only poorly digested by gastrointestinal proteases...

INTRODUCTION: Celiac disease is an immune-mediated gluten-dependent disorder, primarily affecting the small intestine in genetically predisposed individuals. The disorder has a very heterogeneous clinical and histopathological spectrum. Current treatment with a gluten-free diet is very effective, but the diet is difficult to maintain and remains costly. AREAS COVERED: Alternatives to the gluten-free diet have been proposed to either replace this current treatment, or at least, to supplement use of the gluten-free diet...

BACKGROUND & AIMS: Gluten ingestion leads to small intestinal mucosal injury in patients with celiac disease, necessitating strict life-long exclusion of dietary gluten. Despite adherence to a gluten-free diet, many patients remain symptomatic and still have small intestinal inflammation. In this case, nondietary therapies are needed. We investigated the ability of ALV003, a mixture of 2 recombinant gluten-specific proteases given orally, to protect patients with celiac disease from gluten-induced mucosal injury in a phase 2 trial...

Coeliac disease is a permanent immunological intolerance to gluten proteins in genetically predisposed individuals. The only management is life-long strict adherence to a gluten-free diet. Unfortunately, compliance with gluten-free diet is very difficult in practice due to the widespread presence of gluten in Western diets. For this reason, about 50% of coeliacs following a gluten-free diet continue to suffer from symptoms and present with autoantibodies and/or villous atrophy while on a gluten-free diet. It is therefore important to explore new therapies to improve the management of coeliac disease...

BACKGROUND: Celiac disease is the most common hereditary autoimmune disease in humans. The only treatment option for non-refractory celiac disease patients is adherence to a strict life-long gluten-free diet, which often fails to normalize small bowel histology. ALV003 is a mixture of two proteases that degrades gluten and is in clinical development as an oral therapy for patients with celiac disease. AIMS: The safety, tolerability, and activity of ALV003 were assessed in two phase 1 clinical trials...

Effective treatment of celiac disease is an unmet medical need. A glutenase that destroys immunogenic gluten peptides may be clinically valuable. Twenty patients with celiac disease were randomly assigned to ingest a large gluten meal (16 g daily for 3 days) pre-treated with ALV003, a mixture of highly specific glutenases (n=10), or pre-treated with placebo (n=10). Peripheral blood T-cell IFN-gamma ELISpot responses to gliadin and an immunogenic 33mer and symptoms were assessed. While baseline IFN-gamma ELISpot responses to gliadin and the 33mer were negative in all patients, a significant ELISpot response to gliadin or the 33mer was observed in 6 of 10 patients consuming placebo-treated gluten and 0 of 10 consuming ALV003 pre-treated gluten (p=0...