Alvine Pharmaceuticals Presents Results from a Phase 2A Trial of ALV003 in Celiac Disease Patients at the 2012 Digestive Diseases Week Meeting
SAN CARLOS, Calif., May 22, 2012 – Alvine Pharmaceuticals, Inc. today announced the presentation of data from a Phase 2A trial of its lead compound, ALV003, at the 2012 Digestive Diseases Week (DDW) meeting held in San Diego, California. The study results met the primary endpoint of demonstrating that oral ALV003, administered in the context of a gluten free diet (GFD), can diminish gluten-induced intestinal mucosal injury in well-controlled celiac disease patients. The company plans to initiate a Phase 2B trial later this year.
The clinical study presented was a double-blind, placebo-controlled Phase 2A trial evaluating the efficacy and safety of ALV003 administered orally for six weeks. In the study, well-controlled, well-characterized adult celiac disease patients who had been maintained on a GFD for at least one year, were randomized to receive ALV003 or placebo daily for six weeks; patients were instructed to ingest 2g of gluten in the form of bread crumbs at the same meal as the study treatment. Study participants underwent small bowel biopsy prior to randomization and again, at the end of the six week challenge. The study met its primary endpoint, which was a clinically and statistically meaningful difference in intestinal mucosal morphometry (ratio of the villus height to crypt depth, or Vh:Cd) between the ALV003 and placebo treated groups over the six week study period. Secondary endpoints included change in intraepithelial lymphocyte (IEL) density, gastrointestinal symptoms as measured by Gastrointestinal Symptom Rating Scale (GSRS) scores, celiac serologies, safety and tolerability. The main study results were as follows:
- Biopsy data demonstrated significantly reduced small intestinal mucosal injury as measured by Vh:Cd in patients treated with ALV003 than in placebo-treated patients (p=0.0133).
- IELs, including CD3+ and CD3+ αβ and γδ subsets, which measure inflammatory cellular responses were significantly increased in the placebo-treated patients, but were essentially unchanged in the ALV003-treated patients.
- Overall GSRS scores and scores for indigestion and abdominal pain symptoms favored the ALV003-treated patients over the placebo-treated patients, although the results were not statistically significant.
- No statistically significant changes were observed (as expected, given the short duration of the study) in celiac-disease serology tests between the ALV003 and placebo-treated patients, although positive trends were observed for tissue transglutaminase and deamidated gliadin peptide antibody titers in the ALV003-treated group, a measure of immune responsiveness.
- No serious adverse events were reported; non-serious 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, diarrhea, nausea, headache and fatigue.
“This is the first time that we are aware of, that any potential therapeutic intervention in phase 2 development for celiac disease has met its prespecified primary endpoint with both clinical and statistical significance,” said Daniel Adelman, M.D., Alvine’s Senior Vice President and Chief Medical Officer. “We are very encouraged by these results and are currently enrolling celiac disease patients in a study to evaluate and measure celiac-specific symptoms as a function of gluten exposure. In addition, we are planning to initiate a phase 2B clinical trial later this year.”
The abstract of the presentation (Sa1342) can be accessed on the DDW website at: DDW.org.
Information on Alvine’s current clinical trial titled “Evaluation of Patient Reported Outcome Instruments in Celiac Disease Patients” can be found at the NIH website: http://clinicaltrials.gov/ct2/show/NCT01560169
About Celiac Disease
Celiac disease is the most common autoimmune disease, affecting approximately 6 million people in the U.S. and E.U. Celiac disease is an acquired autoimmune disorder that develops in genetically susceptible individuals after exposure to dietary gluten, the protein found in wheat, rye and barley that humans cannot fully digest. Celiac disease is a systemic illness that can affect many organ systems, causing chronic gastrointestinal symptoms, such as nausea, diarrhea, and constipation, and can potentially cause serious medical consequences, including malabsorption, osteoporosis, anemia, infections and malignancies. Currently there is no approved therapy for celiac disease and the only option for patients is to attempt to follow a strict, life-long gluten-free diet.
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 its 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 visit http://www.alvinepharma.com.
Kirk Essenmacher M.D., M.B.A.
Vice President of Marketing, Corporate and Strategic Development
Phone: (650) 596-2434