Alvine Pharmaceuticals, Inc. has announced positive results from its Phase 2a clinical trial of ALV003, which demonstrated the ability of ALV003 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 study findings will be presented in a late breaking oral session at the 19th United European Gastroenterology Week (UEGW) in Stockholm on October 24. The full abstract (#OP050B) can currently be accessed on the UEGW website at http://www.uegw11.uegf.org.
“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,” said Peter Green, M.D., director of The Celiac Disease Center and professor of clinical medicine at Columbia University College of Physicians and Surgeons . “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.”
Phase 2a Trial Design and Results
In the double-blind, placebo-controlled Phase 2a clinical trial, 41 well-controlled, well-characterized adult celiac disease patients were randomized to receive ALV003 or placebo daily for six weeks at the time of ingestion of 2g of gluten (bread crumbs). Study participants underwent small bowel biopsy at the beginning of the trial and after being given the daily gluten challenge for six weeks. The primary endpoint was intestinal villus morphometry (Villus height: Crypt depth, or Vh:Cd) measured at baseline and at six weeks. Secondary endpoints included intraepithelial lymphocyte (IEL) density, gastrointestinal symptoms as measured by Gastrointestinal Symptom Rating Scale (GSRS) scores, celiac serologies, safety and tolerability.
Biopsy results from 34 evaluable patients with celiac disease showed that there was significantly less small intestinal mucosal injury in patients treated with ALV003 than in placebo-treated patients at six weeks (p=0.013). In addition, the data showed statistically significant differences in changes in IEL and both α/β and γ/δ T-lymphocyte subsets.
GSRS scores were directionally consistent with the morphologic changes in the intestinal mucosa (i.e., with less intestinal mucosal injury there was a directionally consistent lower GSRS score). No significant changes were observed in the celiac serology tests. Adverse events consistently occurred more frequently in the placebo-treated patients. Adverse events that occurred in 10 percent or more patients included abdominal distension, flatulence, eructation, abdominal pain and diarrhea.
“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,” said Daniel Adelman, chief medical officer at Alvine Pharmaceuticals.
UEGW Data Presentation and Conference Call Information
The abstract, titled “ALV003, a Novel Glutenase, Attenuates Gluten-Induced Small Intestinal Mucosal Injury in Celiac Disease Patients: A Randomized Controlled Phase 2A Clinical Trial,” will be presented on Monday, October 24, at 2:12 p.m. CEST during the Free Paper Session: Late breaking news in Hall K1/2 by Dr. Markku Mäki, chair and professor of pediatrics at the University of Tampere and Tampere University Hospital in Finland, and lead investigator of the ALV003 Phase 2a trial.
Alvine will host a conference call and webcast to discuss these data and the overall celiac disease space. In addition to Alvine management, Dr. Peter Green will also participate in the conference call. The call will be held Thursday, October 27, at 10:00 a.m. Pacific Time (PT)/1:00 p.m. Eastern Time (ET). The live event will be available from Alvine’s website at http://www.alvinepharma.com, under the News and Media section, or by calling (866) 582-8907 (domestic) or (678) 825-8232 (international). The access code is 15752879. A replay of the webcast will be available from Alvine’s website.
ALV003 is an orally administered mixture of two recombinant gluten-specific proteases, a cysteine protease (EP-B2) and a prolyl endopeptidase (PEP). ALV003 targets gluten and degrades it into small fragments, which, in vitro, diminishes immunogenicity. ALV003 is being developed as a potential treatment for celiac disease patients in conjunction with a gluten-free diet and is currently in Phase 2 clinical development.
Alvine Pharmaceuticals, Inc. is a private, clinical-stage, specialty biopharmaceutical company located in San Carlos, Calif., focused on the development of biologics targeting autoimmune and inflammatory diseases, including celiac disease. Alvine is focusing clinical development efforts on ALV003, an investigational drug in Phase 2 trials that could potentially be the first approved therapeutic treatment for patients with celiac disease. For additional information about the company, please visithttp://www.alvinepharma.com.