SOURCE: Alvine Pharmaceuticals
SAN CARLOS, CA--(Marketwire - Oct 24, 2011) - Alvine Pharmaceuticals, Inc. today announced additional efficacy data from its Phase 2a clinical trial of ALV003. Results showed that oral ALV003, administered in the context of a gluten free diet (GFD), diminished gluten-induced intestinal mucosal injury in well-controlled celiac disease patients. The study findings were presented today in a late-breaking oral session at the 19th United European Gastroenterology Week (UEGW) in Stockholm.
"Although removal of dietary gluten is currently the only treatment option available, up to 60 percent of adult celiac disease patients continue to experience symptoms and up to 80 percent continue to have persistent intestinal inflammation despite adhering to a strict GFD," said Markku Mäki, M.D., chair and professor of pediatrics at the University of Tampere and Tampere University Hospital in Finland, and coordinating investigator of the ALV003 Phase 2a trial. "Gluten ingestion is unavoidable, as gluten is found in a wide variety of products throughout the food supply. Common sources of gluten exposure include cross contamination during food processing, incorrect or inaccurate labeling, lack of patient education and understanding, and dietary indiscretion. Because it is all but impossible to avoid gluten, even while adhering to a GFD, celiac patients are at continued risk for gastrointestinal symptoms and potentially serious long-term medical consequences. New non-dietary treatment options that can either eliminate, or meaningfully reduce the gluten present in an attempted GFD are needed."
Professor Mäki added, "These results are groundbreaking as they demonstrate for the first time, in a controlled clinical trial, that a drug has the potential to diminish gluten-induced injury in celiac disease patients."
Phase 2a Trial Design
In the double-blind, placebo-controlled Phase 2a clinical trial, 41 well-controlled, well-characterized adult celiac disease patients who were maintained on a GFD for one or more years, were randomized to receive ALV003 or placebo daily for six weeks at the time of ingestion of 2g of gluten in the form of 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 mucosal morphometry (Villus height: Crypt depth, or Vh:Cd) measured at baseline and at six weeks. Secondary endpoints included intraepithelial lymphocyte (IEL) density (cells/mm), gastrointestinal symptoms as measured by Gastrointestinal Symptom Rating Scale (GSRS) scores, celiac serologies, safety and tolerability.
Phase 2a Trial Results
The study was statistically powered for the primary endpoint of change in Vh:Cd with six weeks of gluten exposure. Results from 34 celiac disease patients eligible for analysis showed that after six weeks:
- Biopsy data demonstrated significantly less 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+ alpha/beta and gamma/delta subsets, which measure inflammatory response, were essentially unchanged in the ALV003-treated patients but significantly increased in the placebo-treated patients.
||Change from Week 0
to Week 6
||CD3 alpha/beta IELs
||CD3 gamma/delta IELs
- Overall GSRS scores and scores for indigestion and abdominal pain symptoms were lower in ALV003-treated patients than in placebo-treated patients, although the results were not statistically significant.
- No statistically significant changes were observed in celiac disease serology tests between the ALV003 and placebo-treated patients, although positive trends were observed for tissue transglutaminase (tTG) and deamidated gliadin peptide (DGP) antibodies 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, abdominal pain and diarrhea.
"We are grateful to the celiac disease patients who volunteered to participate in this study and to our colleagues in Finland who monitored the progress and safety of the participants. A majority of the patients in our Phase 2a trial had baseline intestinal inflammation even while adhering to a strict GFD, further reinforcing the unmet need in this patient population," said Daniel Adelman, M.D., chief medical officer for Alvine Pharmaceuticals. "The data from this study show that targeting degradation of immunogenic gluten peptides appears to be a viable approach for the development of a non-dietary therapeutic for celiac disease. Based on these trial results, we believe that clinical proof-of-principle has been achieved, and we are targeting 2012 to begin a Phase 2b trial of ALV003 as an adjunct to a GFD in celiac disease patients."
UEGW Data Presentation
The presentation, titled "ALV003, a Novel Glutenase, Attenuates Gluten-Induced Small Intestinal Mucosal Injury in Celiac Disease Patients: A Randomized Controlled Phase 2A Clinical Trial," was given today during the Free Paper Session: Late breaking news in Hall K1/2 by Dr. Mäki. The full abstract (#OP050B) can be accessed on the UEGW website at http://uegw.congress-online.com/guest/AbstractView?ABSID=14408.
Conference Call Information
Alvine will host a conference call and webcast to discuss these data and the overall celiac disease space. In addition to Alvine management, Peter Green, M.D., director of The Celiac Disease Center and professor of clinical medicine at Columbia University College of Physicians and Surgeons, will participate in the conference call. The call will be held on 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 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.
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 difficult to digest protein found in wheat, rye and barley. It is a systemic illness that affects 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, malignancies and an increased mortality rate. Currently there is no approved therapy for celiac disease and the only treatment option for patients is to attempt to follow a strict, life-long gluten-free diet (GFD).
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 visit http://www.alvinepharma.com.