NasVax reports positive results from Phase 2a trial of oral immunotherapy for non-alcoholic steatohepatitis

Mar 21 2011

NasVax (TASE: NSVX) ("Company") announces the success of a Phase 2a clinical trial of a new oral immunotherapy for non-alcoholic steatohepatitis (NASH), an inflammatory disease associated with fatty liver disease and the metabolic syndrome.

“This initial demonstration of positive proof of clinical benefit in an inflammatory disease is very encouraging as NasVax continues to develop this novel immunotherapy, which may be beneficial for a range of inflammatory and autoimmune indications having very large market potential and in need of improved therapies.”

This Phase 2a trial investigated each of three dosage levels (0.2, 1.0, 5.0 mg) of anti-CD3 monoclonal antibody (MAb) given orally once daily for 30 days, with a final follow-up 30 days later (60 days after the first dose). Evaluations were for safety as primary endpoint, for immunological effects as co-primary endpoint, and for clinical efficacy effects as secondary endpoint. The trial was a single-blind randomized placebo-controlled study that enrolled 36 subjects aged 18-75 with NASH and altered glucose metabolism and included subjects with type-2 diabetes, and was conducted at the Hadassah-Hebrew University Medical Center in Jerusalem, Israel.

The clinical trial successfully met all three endpoints.

Safety:

The immunotherapy was found to be very safe and well tolerated, with no drug-related adverse effects or systemic complaints in any of the three dosage groups, as measured by blood hematology, chemistry, immunological safety markers and general physical signs. During the course of immunotherapy and compared to placebo, there were no changes in blood levels of CD3-positive cells or of CD4-positive or CD8-positive cells which are indicators of immunological safety. Some subjects had increased levels of serum antibodies directed against the MAb, which did not affect the positive trial results observed. These results indicate that there were no adverse systemic or local effects of anti-CD3 MAb. The safety data are consistent with the Phase 1 safety data for oral anti-CD3 immunotherapy in healthy subjects.

Clinical efficacy parameters:

The immunotherapy resulted in positive trends in clinical parameters in groups receiving oral anti-CD3 but not in the placebo group - some of these trends were statistically significant in spite of the very small group sizes. These positive effects on efficacy were reduced blood levels of a liver enzyme indicating reduced liver inflammation, and reduced blood levels of glucose and insulin, which are favorable outcomes for subjects with NASH or metabolic syndrome and for subjects with type-2 diabetes or altered glucose metabolism. Several of the positive efficacy trends persisted to Day 60 following cessation of immunotherapy at Day 30. These clinical data suggest that oral anti-CD3 MAb immunotherapy may have clinical benefit for subjects with NASH or type-2 diabetes.

Immunological markers:

The immunotherapy induced regulatory T cells, which generally persisted to Day 60. Subjects in groups receiving the MAb showed increases in such markers, while those receiving placebo did not show such increases. Other immunomodulatory effects included trends in the induction of cytokines, which are natural molecules that influence the immune system. These immunological changes during the course of therapy are generally consistent with those observed during the Phase 1 clinical study as well as in multiple studies in animal model systems that demonstrated the relationship between induced regulatory T cells and selective suppression of certain inflammatory and autoimmune diseases with a good safety and immunological profile.

About 8 million people in the US alone suffer from fatty liver disease, and an additional 30 million might be afflicted with a milder form of this condition. Fatty liver disease appears in about 5% of the non-obese population, in up to 20% in obese people, and in up to 50% in people with morbid obesity. The disease may lead to cirrhosis of the liver or liver cancer. Currently there are no licensed drugs for this condition. The market value in 2009 was estimated at $1.8 billion with an annual growth of 8.4%, and is expected to reach $3.1 billion in 2016 (Global Data 2010). There are other therapeutic modalities under development that are based on technologies different from oral anti-CD3 immunotherapy.

Published and experimental results in animal studies including models of type 1 and type 2 diabetes, inflammatory bowel disease, rheumatoid arthritis, lupus, multiple sclerosis, and atherosclerosis show that oral anti-CD3 MAb immunotherapy selectively suppresses certain inflammatory and autoimmune diseases. The markets for these and other potential disease indications are in need of improved therapies, and the values of most of these are $ billions. Patent claims for oral anti-CD3 immunotherapy in a number of disease indications have been allowed in the US.

This therapy was discovered by Howard L. Weiner, MD, the Robert Kroc Professor of Neurology at the Harvard Medical School and the Director and Founder of the Partners Multiple Sclerosis Center at Brigham and Women's Hospital (BWH) in Boston, and was licensed from Hadasit. Dr. Weiner is a world-renowned expert in the field of oral immunotherapy and a consultant to the Company. The exclusive license to this technology was granted to NasVax from Hadasit following collaboration between BWH and Hadassah that resulted in successful preclinical studies at Hadassah in animal models of type-2 diabetes and inflammatory liver diseases and that was followed by a successful Phase 1 clinical trial in 18 volunteers.

Dr. Howard Weiner said, "The demonstration of clinical improvement in subjects with fatty liver disease provides initial clinical validation that the induction of regulatory T cells by oral anti-CD3 immunotherapy can result in clinical benefit with an excellent safety profile. We look forward to further development of this novel immunotherapy in both fatty liver disease and other targets of inflammation and autoimmunity."

Dr. Rom Eliaz, CEO of NasVax, said, "This initial demonstration of positive proof of clinical benefit in an inflammatory disease is very encouraging as NasVax continues to develop this novel immunotherapy, which may be beneficial for a range of inflammatory and autoimmune indications having very large market potential and in need of improved therapies."