Results of a Drug Trial Conducted in Finland in Celiac Disease Patients Presented at the United European Gastroenterology Week Meeting in Stockholm

Alvine Pharmaceuticals, Inc. California, USA, announced positive results from its phase 2a celiac disease trial with ALV003 at the United European Gastroenterolgy Week (UEGW) scientific meeting in Stockholm. In this clinical trial it was shown that ALV003 diminished gluten-induced intestinal mucosal injury in celiac disease. The study was conducted as a multicenter trial in Finland, coordinated by FinnMedi Oy. Based on the positive phase 2a results, a phase 2b clinical trial is targeted to start in 2012.

The clinical trial was conducted in Finland (Tampere, Kuopio, Oulu). Six doctors and five study nurses worked in the study centers. Trial operative functions were led by Tiina Kärjä-Lahdensuu FinnMedi Oy (operative functions and regulatory), and researchers in Tampere University Celiac Disease Research Group: Marja-Leena Lähdeaho, MD (Principal Investigator) and Professor Markku Mäki (celiac disease scientific research, Coordinating Responsible investigator in charge of patient safety in Finland).

“Clinical research makes it possible for new treatments to be available in the future,” said Tiina Kärjä-Lahdensuu. “This clinical trial was the fourth trial in celiac disease completed in collaboration with FinnMedi Oy, University of Tampere and Tampere University Hospital in Finland. These preliminary positive results encourage us to continue collaborating with the Biopharmaceutical Industry at an international level.”

“I’d like to express my gratitude to the Celiac Disease Patient Association in Finland and its member associations, who have improved the lives of celiacs with their long term work and increased awareness of celiac disease in Finland.  A special thanks to all celiac patients who volunteered to participate in clinical trials of novel compounds targeting celiac disease; without them this trial could not have been completed,” added Kärjä-Lahdensuu.
Given the results of this phase 2a study, the pharmaceutical company will continue their clinical research program in the coming years.

“There are currently no approved therapies for celiac disease. Strict, life-long adherence to a gluten-free diet is the current standard of care and the only treatment option for these patients, but this does not offer a comprehensive solution,” says Marja-Leena Lähdeaho, Principal Investigator.  “A gluten-free diet does not completely prevent exposure to gluten and does not affect the underlying cause of disease, potentially leaving patients vulnerable to the effects of gluten on gastrointestinal symptoms and the potential for serious long-term medical consequences.”

Clinical Trial Design and Results

Forty-one well-controlled celiac disease patients who were maintained on a GFD for one or more years participated in the trial. Half of study patients received ALV003 as study drug and the other half received placebo for six weeks at the time of ingestion of 2g of daily gluten (equivalent to approximately one-half of a slice of bread). Study participants underwent small bowel biopsy at the beginning of the trial and at the end of the trial.  The primary endpoint was intestinal mucosal changes caused by gluten, which were evaluated from the biopsy samples taken.

Additionally mucosal intraepithelial lymphocyte (IEL) density was evaluated at the beginning and end of the trial. Blood samples were taken for antibody evaluation common in celiac disease and also to ensure study drug safety. Gastrointestinal symptoms were measured with a symptom questionnaire. Also study drug safety and tolerability was evaluated.
Biopsy results showed that after six weeks exposure to gluten, there was significantly less small intestinal mucosal injury in patients given with ALV003 than in placebo-treated patients. In addition, the data showed significant differences in changes in IEL between the study groups.

“Based on the results of this rigorously conducted and controlled clinical 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,” tells Daniel Adelman, chief medical officer at Alvine Pharmaceuticals.

“These results are important 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” said Markku Mäki, Director of Celiac Disease Research Group, Professor at the University of Tampere.

Additional information:

Conducting the clinical trial:
Tiina Kärjä-Lahdensuu, Clinical Research Director, FinnMedi Oy, tel. +358 400 678 332, tiina.karja-lahdensuu(at)finnmedi.com

Celiac Disease Research and Celiac Disease:
Marja-Leena Lähdeaho, MD, Principal Investigator in the trial, University of Tampere, tel. +358 50 433 0702, marja-leena.lahdeaho(at)uta.fi

Markku Mäki, Professor, Director of the Celiac Disease Research Group, University of Tampere, tel. +358 50 365 6668, markku.maki(at)uta.fi

UEGW Data Presentation and Conference Call
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 presented by Professor Markku Mäki in the scientific conference UEGW in Stockholm, on Monday 24 Oct 2011. The abstract (#OP050B) can be accessed on the UEGW website at http://uegw.congress-online.com/guest/AbstractView?ABSID=14408.
Markku Mäki works as a Professor at the University of Tampere and Chief Physician in the pediatrics clinic at Tampere University Hospital as well as a Director of Celiac Disease Research Group. Mäki has been the Coordinating Responsible Investigator in this clinical drug trial.

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 New York, will participate in the conference call. The call will be held on Thursday, October 27, at 20:00 Finnish time. The live event will be available from Alvine's website at www.alvinepharma.com, under the News and Media section, or by calling +1 678 825-8232 (international). The access code is 15752879. If you are unable to participate in the live call, 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 human body system is not able to digest protein found in wheat, rye and barley.  Celiac disease 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, celiac disease affecting skin (DH,) liver disease, nervous system problems, 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).

About ALV003
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.

About Alvine
Alvine Pharmaceuticals, Inc. is a private company located in San Carlos, California, USA focused on the development of biologics targeting autoimmune and inflammatory diseases.  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.

FinnMedi Oy
FinnMedi is a company located at Tampere focusing on life science sector services, which owners are Pirkanmaa Hospital District, City of Tampere, Tampere University and Tampere Technical University and Red Cross. Trough FinnMedi there is access to the leading national and international scientific know-how, experienced researchers, university hospitals, life science companies, ventures and other networks, as well as close collaboration together with the researchers at the University of Tampere and University Hospital. Additional information: www.finnmedi.com.