Alvine Pharmaceuticals Announces Positive Results from Phase 2a Trial of ALV003

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 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.

Green continued, "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 alpha/beta and gamma/delta 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.