October 29, 2008
Alvine Pharmaceuticals Reports Positive Results With ALV003 in Phase 1 Trial of Therapy in Development for Celiac Disease
Alvine Pharmaceuticals, Inc., today announced proof of concept in a Phase 1 Trial of ALV003, an oral protease therapy in development to detoxify gluten, intended for use by patients with celiac disease. The trial results confirmed that single doses of up to 1,800 mg of ALV003 were safe and tolerable in healthy volunteers. Doses at the 300 mg level achieved up to a 96% reduction of gluten in a meal in the stomach at 30 minutes, and were well tolerated by patients with celiac disease. In addition, doses as low as 100 mg were shown to be biologically active in degrading gluten in the stomach. Based on these results, Alvine plans to initiate Phase 1/2a multidose trials in early 2009.
"The outcome of the Phase 1 Trial of ALV003 is a major step toward providing people with celiac disease a better quality of life, as there are currently no approved pharmaceutical therapies available," said Dr. Ciaran P. Kelly, Medical Director of the Celiac Center at Beth Israel Deaconess Medical Center and Harvard Medical School. "Given the difficulty of following a strict gluten free diet, and the potentially serious health consequences of gluten exposure, there is a great medical need for ALV003 and other new therapies targeting celiac disease."
In addition to reporting Phase 1 results today, Alvine presented data in October, 2008 at the United European Gastroenterology Week conference in Vienna, Austria from a study in patients with celiac disease. The study demonstrated that patients with celiac disease who ingested gluten pre-treated with ALV003 showed elimination of peripheral gluten specific reactive T cells as measured by ELISpot responses. The study, conducted at the Alfred Hospital and Burnet Institute in Melbourne, Australia, suggests that a gluten specific ELISpot response may be a useful test for assessing the effectiveness of therapeutics in subjects with celiac disease.
"Results from these studies support the use of ALV003 as a drug to be taken with meals to address unintentional gluten exposure. In addition, the ELISpot study provides evidence that treatment of gluten with ALV003 may result in a reduction in the immune response to gluten in patients with celiac disease," said Dr. Peter H. R. Green, Professor of Clinical Medicine and Director of the Celiac Disease Center at Columbia University. "These results provide a strong rationale to advance the clinical development of this compound as a treatment for celiac disease."
ALV003 is an orally administered combination of two proteases engineered to degrade gluten into non-immunotoxic fragments, by targeting the glutamine and proline residues that are common in gluten. ALV003 consists of a glutamine specific cysteine protease (EP-B2) and a proline specific prolyl endopeptidase (PEP).
About Celiac Disease
Celiac disease is the most common hereditary autoimmune disease with prevalence as high as 2% in the U.S. and E.U. Celiac disease is triggered by the ingestion of gluten in genetically susceptible individuals. Gluten is a protein found naturally in wheat, rye, and barley, and is one of the most common food additives in the human diet. Patients with celiac disease mount an immune response to gluten and gluten fragments, resulting in systemic immune mediated damage in the gut and other organs. Gluten ingestion can be associated with symptoms such as nausea, diarrhea, constipation and rash. Complications of celiac disease can include osteoporosis, anemia, dermatitis, weight loss, diabetes, central nervous system conditions, other autoimmune diseases and malignancies. The only available option for individuals diagnosed with celiac disease is a life-long adherence to a strict gluten-free diet, which is difficult to follow.
Alvine Pharmaceuticals, Inc. is a privately held biopharmaceutical company dedicated to developing and commercializing therapeutics for autoimmune/gastrointestinal diseases. Alvine's lead product candidate, ALV003, is a combination protease engineered to degrade gluten, and is being developed to treat patients with celiac disease. For additional information about the company, please visit www.alvinepharma.com.