-- Growing Identification of HSCT-TMA a Focus of Recent Annual Meeting of the European Society for Blood and Marrow Transplantation --
Omeros Corporation (OMER) today announced the recent presentation of a case report describing resolution of gastrointestinal hematopoietic stem cell transplant-associated thrombotic microangiopathy (HSCT-TMA) following narsoplimab treatment under a compassionate-use protocol. The case was presented at the 2019 Annual Meeting of the European Society for Blood and Marrow Transplantation (EBMT) held March 24-27 in Frankfurt, Germany. Omeros is reporting the case to ensure broad availability of the information presented. Narsoplimab, Omeros’ antibody to inhibit the lectin pathway of complement, has received breakthrough therapy designation from FDA and is in Phase 3 development for the treatment of HSCT-TMA.
The case was presented by Rafael Duarte M.D., Ph.D., F.R.C.P., Associate Professor, Head of Hematopoietic Transplantation and Hemato-oncology Section, University Hospital Puerta de Hierro Majadahonda, Madrid, Spain, and Secretary of the EBMT. Dr. Duarte described an 18-year-old patient with biopsy-proven HSCT-TMA of the gastrointestinal tract causing severe gastrointestinal bleeding requiring transfusions. The patient received narsoplimab, her TMA resolved, and all transfusions have been discontinued. The patient continues to do well after cessation of narsoplimab treatment.
Hematopoietic stem cell transplant-associated TMA was a focus of the EBMT meeting program. In addition to the educational course on early transplant complications that included Dr. Duarte’s presentation, the program included a review session on renal complications of HSCT-TMA and an Omeros-sponsored symposium entitled “How Do I Diagnose HSCT-TMA.” All of these sessions were well attended. The meeting program also contained several other podium and poster presentations directed to complications related to endothelial injury, which include HSCT-TMA, graft-versus-host disease and diffuse alveolar hemorrhage.
The interest in HSCT-TMA shown at the EBMT meeting tracks a broadening recognition of the high incidence and severity of this transplant complication. This growing awareness within the stem-cell transplant community is further reflected by the increasing frequency of compassionate-use requests from physicians worldwide seeking narsoplimab treatment for adult and pediatric patients with HSCT-TMA. Historically, the literature-based incidence of HSCT-TMA has been varied, with some smaller centers and national registries reporting low numbers of cases while major research institutions reported incidences in the range of 15-25 percent. More recently, however, as TMA has become better understood and identified, its reported occurrence has been approximately 40 percent in patients undergoing allogeneic HSCT in centers that screen for the disease. The condition is associated with an increased mortality rate and, even in those patients who survive, it often causes chronic kidney damage.
Omeros is preparing both a U.S. biologics license application (BLA) and a European marketing authorization application for narsoplimab in the treatment of HSCT-TMA. The FDA has agreed that a rolling BLA submission is appropriate and discussions with European regulators are ongoing.
About Omeros’ MASP Programs
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 is the effector enzyme of the lectin pathway, one of the principal complement activation pathways. 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 circulation. Gene-targeted MASP-2-deficient mice and humans with MASP-2 gene polymorphisms that affect MASP-2 serum levels and MASP-2 functional activity are generally healthy with no obvious adverse phenotype.
Phase 3 clinical programs are in progress for narsoplimab, Omeros’ lead MASP-2 inhibitor also referred to as “OMS721,” in hematopoietic stem cell transplant-associated thrombotic microangiopathy (HSCT-TMA), in immunoglobulin A (IgA) nephropathy, and in atypical hemolytic uremic syndrome (aHUS). Narsoplimab can be administered both intravenously and subcutaneously, and Omeros expects to commercialize each formulation of narsoplimab for different therapeutic indications. In parallel, Omeros is developing small-molecule inhibitors of MASP-2. Based on requests from treating physicians, Omeros has established a compassionate-use program for narsoplimab, which is active in both the U.S. and Europe. The FDA has granted narsoplimab breakthrough therapy designation for IgA nephropathy and for HSCT-TMA, orphan drug status for the prevention (inhibition) of complement-mediated thrombotic microangiopathies, for the treatment of IgA nephropathy, for the treatment of HSCT-TMA, and fast track designation for the treatment of patients with aHUS. The European Medicines Agency has granted orphan drug designation to narsoplimab for treatment of primary IgA nephropathy and for treatment in HSCT.
Omeros also has identified MASP-3 as responsible for the conversion of pro-factor D to factor D and as a critical activator of the human complement system’s alternative pathway. The alternative pathway is linked to a wide range of immune-related disorders. In addition to its lectin pathway inhibitors, the company is advancing its development of antibodies and small-molecule inhibitors against MASP-3 to block activation of the alternative pathway. Omeros has initiated the manufacturing scale-up process of its MASP-3 antibodies in preparation for clinical trials.
About Omeros Corporation
Omeros is a commercial-stage biopharmaceutical company committed to discovering, developing and commercializing small-molecule and protein therapeutics for large-market as well as orphan indications targeting inflammation, complement-mediated diseases, disorders of the central nervous system and immune-related diseases, including cancers. The company’s drug product OMIDRIA (phenylephrine and ketorolac intraocular solution) 1% / 0.3% is marketed for use during cataract surgery or intraocular lens (IOL) replacement to maintain pupil size by preventing intraoperative miosis (pupil constriction) and to reduce postoperative ocular pain. In the European Union, the European Commission has approved OMIDRIA for use in cataract surgery and other IOL replacement procedures to maintain mydriasis (pupil dilation), prevent miosis (pupil constriction), and to reduce postoperative eye pain. Omeros has multiple Phase 3 and Phase 2 clinical-stage development programs focused on: complement-associated thrombotic microangiopathies; complement-mediated glomerulonephropathies; cognitive impairment; and addictive and compulsive disorders. In addition, Omeros has a diverse group of preclinical programs and a proprietary G protein-coupled receptor (GPCR) platform through which it controls 54 new GPCR drug targets and corresponding compounds, a number of which are in preclinical development. The company also exclusively possesses a novel antibody-generating platform.
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