Phase 2 Clinical Trial in aHUS and Other TMAs Expected to Begin Next Quarter
March 10, 2014
Omeros Corporation today announced positive data using OMS721, the lead human monoclonal antibody in Omeros’ mannan-binding lectin-associated serine protease-2 (MASP-2) program, in ex vivo studies of endothelial activation relevant to the pathophysiology of human atypical hemolytic uremic syndrome (aHUS), a form of thrombotic microangiopathy (TMA). TMAs are a family of rare, debilitating and life-threatening disorders characterized by multiple thrombi (clots) in the microcirculation of the body’s organs, most commonly the kidney and brain. In February, Omeros reported positive results from its OMS721 Phase 1 clinical trial and, earlier this month, announced submission of an investigational new drug application to the U.S. Food and Drug Administration (FDA) to initiate a Phase 2 clinical trial in patients with TMA, including patients with aHUS.
The data announced today resulted from studies conducted in support of the clinical evaluation of OMS721 by Prof. Giuseppe Remuzzi and colleagues Marina Noris and Miriam Galbusera at the Mario Negri Institute for Pharmacological Research in Bergamo, Italy, and the Clinical Research Center for Rare Diseases “Aldo e Cele Daccò″ of the same Institute, a European center for collecting and studying TMA samples. The experimental model is based on the finding that serum samples from aHUS patients cause complement deposition and thrombus formation when incubated with human microvascular endothelial cells. The data reported today showed that OMS721 significantly inhibited complement deposition in the model using serum samples from aHUS patients obtained during the acute phase of disease (p<0.01) and during remission (p<0.001) compared to untreated controls. Experiments evaluating the effects of OMS721 on thrombus formation are planned. Prof. Remuzzi’s laboratories have previously shown in this same model system that treatment with agents that block the complement factor C5 has a similar inhibitory effect on complement deposition. Eculizumab (Soliris®) is an anti-C5 monoclonal antibody that is approved by the FDA and the European Medicines Agency to treat patients with aHUS.
“The OMS721 data in serum samples from aHUS patients are of great interest even in relation to disease pathophysiology,” stated Prof. Remuzzi, MD, FRCP, Research Coordinator at the Institute and international expert in the study of kidney disease who has contributed major advances to the understanding of the pathophysiology of hemolytic uremic syndrome.
“We are excited by the performance of OMS721 in serum samples from aHUS patients,” stated Gregory A. Demopulos, M.D., chairman and chief executive officer of Omeros. “These data indicate that the lectin pathway, and MASP-2 specifically, are involved in the pathophysiology of aHUS, one of the devastating TMAs. We look forward to initiating enrollment next quarter in our OMS721 Phase 2 trial in patients with aHUS and other TMAs, and we hope to be able to share the results later this year.”
About Omeros’ MASP-2 Program
Omeros controls the worldwide rights to MASP-2 and all therapeutics targeting MASP-2, a novel pro-inflammatory protein target involved in activation of the complement system, which is an important component of the immune system. The complement system plays a role in the inflammatory response and becomes activated as a result of tissue damage or microbial infection. MASP-2 appears to be unique to, and required for the function of, one of the principal complement activation pathways, known as the lectin pathway. Importantly, inhibition of MASP-2 does not appear to interfere with the antibody-dependent classical complement activation pathway, which is a critical component of the acquired immune response to infection, and its abnormal function is associated with a wide range of autoimmune disorders. MASP-2 is generated by the liver and is then released into the circulation. Adult humans who are genetically deficient in one of the proteins that activate MASP-2 do not appear to be detrimentally affected by the deficiency. Therefore, Omeros believes that it may be possible to deliver MASP-2 antibodies systemically and OMS721, its lead MASP-2 antibody, is designed to be self-administered by subcutaneous injection.
Omeros also believes that it has identified the proteins that activate the complement system’s alternative pathway in humans, which is linked to a wide range of immune-related disorders. In addition to its lectin pathway inhibitors, the Company is advancing the development of antibodies that would block activation of the alternative pathway alone or in combination with the lectin pathway.
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