According to an announcement made today by Alvine Pharmaceuticals, Inc., the Phase 2a clinical trial of ALV003 produced positive results, demonstrating its ability to attenuate gluten-induced intestinal mucosal injury in serologically negative celiac disease patients maintained on a gluten-free diet for one or more years.
The results of the study will be presented on October 24 at the 19th United European Gastroenterology (UEGW) in Stockholm in the late breaking news. The full report (#OP050B) can currently be viewed on the UEGW website at www.uegw11.uegf.org.
Peter Green, M.D., director of The Celiac Disease Center and professor of clinical medicine at Columbia University College of Physicians and Surgeons commented:
"There are currently no approved therapies for celiac disease. Strict, life-long adherence to a gluten-free diet (GFD) is the current standard of care and the only treatment option for these patients, but this does not offer a comprehensive solution."He continued saying that: "A GFD does not completely prevent exposure to gluten and does not affect the underlying cause of disease, potentially leaving patients vulnerable to gastrointestinal symptoms and serious long-term medical consequences."
Design and Results of Phase 2a TrialResearchers conducted a double blind, placebo-controlled Phase 2a clinical trial involving 41 well controlled, well-characterized adult celiac disease patients. The participants were randomized to be daily administered with either ALV003 or placebo at the time of ingestion of 2g of gluten (bread crumbs) for the duration of six weeks.
All participants underwent a small bowel biopsy at the beginning of the trial and at the end of the six-week long daily gluten challenge. The study's primary endpoint was intestinal villus morphometry (Villus height: Crypt depth, or Vh:Cd) measured at baseline and at six weeks. Researchers determined the secondary endpoints in terms of intraepithelial lymphocyte (IEL) density, gastrointestinal symptoms as measured by Gastrointestinal Symptom Rating Scale (GSRS) scores, celiac serologies, safety and adverse effects.
The biopsy findings of 34 evaluable celiac patients revealed that small intestinal mucosal injury was substantially lower in the ALV003-group compared with the placebo group at six weeks (p=0.013). Data also showed substantial statistical differences in IEL changes and changes in both alpha/beta and gamma/delta T-lymphocyte subsets.
GSRS scores proved to be directionally steady with morphologic changes in the intestinal mucosa, meaning that with less intestinal mucosal injury the GSRS score was also consistently lower. Researchers observed no substantial changes in the celiac serology tests. The placebo group experienced more frequent adverse events throughout with more than 10% of participants suffering from abdominal distension, flatulence, eructation, abdominal pain and diarrhea.
Daniel Adelman, chief medical officer at Alvine Pharmaceuticals stated:
"Based on the results of this rigorously conducted trial, we believe that clinical proof-of-principle has been achieved. We are currently preparing for a Phase 2b trial of ALV003 in celiac disease patients targeted to begin in 2012."
Celiac DiseaseAbout 6 million people in the E.U. and U.S suffer from Celiac disease, the most common autoimmune disease, which is an acquired autoimmune disorder that develops in genetically susceptible individuals damaging the lining of the small intestine and preventing it from absorbing parts of food important for staying healthy.
The damage is due to a reaction to eating gluten, which is found in wheat, barley and rye. A systemic illness affecting many organ systems, Celiac disease causes chronic gastrointestinal symptoms, such as nausea, diarrhea, and constipation. It can potentially lead to serious medical conditions, such as anemia, osteoporosis, malabsorption, end-stage renal disease, malignancies, infections and increased mortality rates. At present the only option of treatment for Celiac Disease patients is to follow a strict, life-long gluten-free diet (GFD) as there are no approved therapies available.
Duodenum of person with celiac disease - see scalloping of folds and "cracked-mud" appearance of mucosa
About ALV003Developed as a potential therapy for celiac disease patients, ALV003 is administered in conjunction with a gluten-free diet and contains a mixture of two recombinant gluten-specific proteases, EP-B2, a cysteine protease and PEP, a prolyl endopeptidase. The orally administered mixture targets gluten, breaking it down into small fragments, which, in vitro, diminishes immunogenicity. At present, ALV003 is undergoing Phase 2 clinical development.
Written by Petra Rattue