29 August 2018 - - The European Commission has adopted a decision designating OMS721 as an Orphan Medicinal Product in the European Union for treatment in hematopoietic stem cell transplantation, US-based biopharmaceutical company Omeros Corp. (NASDAQ: OMER) said.

Adoption by the EC follows a positive opinion for orphan designation of OMS721 in this indication by the European Medicines Agency's Committee for Orphan Medicinal Products.

OMS721 is Omeros' lead human monoclonal antibody targeting mannan-binding lectin-associated serine protease-2 (MASP-2), the effector enzyme of the lectin pathway of the complement system.

There are three Phase 3 development programs ongoing with OMS721 in each of HSCT-associated thrombotic microangiopathy, atypical hemolytic uremic syndrome, and immunoglobulin A nephropathy.

This represents the second orphan drug designation in Europe for OMS721, with the first being for OMS721 in the treatment of primary IgA nephropathy.

Orphan drug designation in Europe is available to companies developing products intended to treat a life-threatening or chronically debilitating condition that affects fewer than five in 10,000 persons in the EU. 

This designation allows for financial and regulatory incentives that include a 10-year period of marketing exclusivity in the EU after product approval, protocol assistance from the EMA at reduced fees during the product development phase, and access to centralised marketing authorisation.

OMS721 also has been granted orphan designations from the US Food and Drug Administration (FDA) for indications related to both HSCT-associated TMA and IgA nephropathy.

Omeros said it is in discussions with European regulators and FDA to discuss full and conditional/accelerated approval for OMS721 in HSCT-associated TMA.

The company 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 range of autoimmune disorders.

MASP-2 is generated by the liver and is then released into 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. OMS721 is Omeros' lead human MASP-2 antibody.

Phase 3 clinical programmes are in progress for OMS721 in atypical hemolytic uremic syndrome, in immunoglobulin A nephropathy and in hematopoietic stem cell transplant-associated thrombotic microangiopathy (HSCT-TMA).

Also, two Phase 2 trials are ongoing. One is continuing to enroll IgA nephropathy patients and has already generated positive data in patients with IgA nephropathy and with lupus nephritis; the other is enrolling and has reported positive data in patients with HSCT-TMA and in patients with aHUS. OMS721 can be administered both intravenously and subcutaneously, and Omeros expects to commercialize each formulation of OMS721 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 OMS721, which is active in both the US and Europe.

The FDA has granted OMS721 breakthrough therapy designation for IgA nephropathy and for high-risk HSCT-TMA, orphan drug status for the prevention (inhibition) of complement-mediated thrombotic microangiopathies and for the treatment of IgA nephropathy, and fast track designation for the treatment of patients with aHUS.

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.

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 and disorders of the central nervous system.