Omeros Updates Zaltenibart Phase 3 PNH Trial
Omeros Corporation (Nasdaq: OMER) has announced significant progress in its Phase 3 clinical trial program for zaltenibart (OMS906), an investigational inhibitor of MASP-3, the key and most proximal activator of the alternative pathway of complement. This trial aims to evaluate zaltenibart’s efficacy in treating paroxysmal nocturnal hemoglobinuria (PNH), a rare and life-threatening blood disorder. The drug is designed to inhibit both intravascular hemolysis, which is typically treated by C5 inhibitors, and extravascular hemolysis, which is exacerbated by C5 inhibitors, while preserving the classical pathway’s lytic function essential for infection defense.
The clinical trial program for zaltenibart is being conducted across 120 investigative sites spanning 30 countries. Many of these sites have already identified patient pools for participation, and Omeros is actively working with them to recruit additional eligible candidates. The company remains on track to gather the necessary data for submitting the Biologics License Application (BLA) and global approval dossiers for zaltenibart by the fourth quarter of 2026.
A distinguishing feature of zaltenibart is its dosing schedule. Unlike currently available upstream complement inhibitors, which require frequent administration—either orally twice or three times daily in combination with a C5 inhibitor or through subcutaneous infusions twice weekly—zaltenibart is administered intravenously once every eight weeks. This infrequent dosing regimen, combined with the drug’s ability to inhibit both types of hemolysis, offers a significant advantage over existing PNH therapies.
Previous Phase 2 trial data, presented at the American Society of Hematology and European Hematology Association Annual Meetings, demonstrated that zaltenibart effectively prevents both intravascular and extravascular hemolysis, achieving gender-normal hemoglobin levels in male and female patients alike. Importantly, no significant safety concerns have been observed with zaltenibart during these studies.
The Phase 3 clinical trial program consists of two separate studies: one focusing on patients who are not currently receiving complement-inhibitor therapy and another targeting those with inadequate responses to existing C5 inhibitors, such as ravulizumab or eculizumab. Both trials will compare the efficacy and safety of zaltenibart monotherapy against C5 inhibitors. Regulatory agencies, including the FDA and European authorities, have endorsed these trial designs.
All necessary zaltenibart drug product for the Phase 3 studies has already been manufactured, and comparator C5 inhibitors have been sourced. The study’s head-to-head comparisons aim to generate robust data demonstrating the superiority of zaltenibart over existing treatments. If successful, these findings could support comparative superiority claims, aiding in market positioning, pricing strategies, and reimbursement negotiations.
To further strengthen its commercial strategy, Omeros has incorporated patient-reported outcome (PRO) measures into the Phase 3 trial design. These measures, recommended by the German Federal Joint Committee, assess treatment impact from the patient’s perspective and are expected to play a crucial role in justifying appropriate pricing and reimbursement.
Gregory A. Demopulos, M.D., Chairman and CEO of Omeros, expressed optimism regarding the trial’s progress. “We are pleased that the Phase 3 clinical program for zaltenibart is well underway. Phase 2 data have highlighted key differentiators from existing therapies, and we anticipate that these advantages will be further confirmed in Phase 3. Our goal is to refine and optimize the commercial potential of zaltenibart while delivering a superior treatment option to PNH patients and their physicians.”
The market for PNH therapies is expanding rapidly, with a reported valuation of $3.8 billion in 2023, projected to exceed $11.7 billion by 2034. Beyond PNH, Omeros is also investigating zaltenibart for other indications related to the alternative pathway. A Phase 2 clinical trial is currently underway to assess zaltenibart’s potential in treating C3 glomerulopathy, and additional studies are being planned for other related conditions.
With its unique mechanism of action, convenient dosing schedule, and promising efficacy data, zaltenibart has the potential to revolutionize PNH treatment. As the Phase 3 trials progress, Omeros remains committed to advancing innovative therapies that address critical unmet needs in hematology and immunology.
About Zaltenibart (OMS906)
Zaltenibart is an investigational human monoclonal antibody targeting mannan-binding lectin-associated serine protease-3 (MASP-3), the key and most proximal activator of the complement system’s alternative pathway. The complement system is a critical part of innate immunity and plays a central role in host homeostasis and defense against pathogens. Responsible for the conversion of pro-complement factor D to complement factor D, MASP-3 is believed to be the premier target in the alternative pathway – it has the lowest native circulating level and low relative clearance compared to the other alternative pathway proteins and, unlike C5 and C3 blockers, MASP-3 inhibition leaves intact the lytic arm of the classical pathway, important for fighting infection. Also, unlike other components of the alternative pathway, MASP-3 is believed not to be an acute phase reactant, which could provide a significant advantage to MASP-3 inhibitors, like zaltenibart, over other alternative pathway inhibitors. MASP-3 inhibitors are thought to have preventive or therapeutic effects across a broad range of diseases including paroxysmal nocturnal hemoglobinuria (PNH), hemolytic uremic syndrome (HUS), atypical HUS, traumatic brain injury, arthritis, geographic atrophy or “dry” macular degeneration, ischemia-reperfusion injury, transplant-related complications and other immune-related disorders.
About Omeros Corporation
Omeros is an innovative biopharmaceutical company committed to discovering, developing and commercializing first-in-class small-molecule and protein therapeutics for large-market and orphan indications targeting immunologic disorders, including complement-mediated diseases and cancers, as well as addictive and compulsive disorders. Omeros’ lead MASP-2 inhibitor narsoplimab targets the lectin pathway of complement and is the subject of a biologics license application pending before FDA for the treatment of hematopoietic stem cell transplant-associated thrombotic microangiopathy. Omeros’ long-acting MASP-2 inhibitor OMS1029 has successfully completed Phase 1 single- and multiple-ascending dose clinical studies. Zaltenibart, Omeros’ inhibitor of MASP-3, the key activator of the alternative pathway of complement, is advancing toward Phase 3 clinical trials for paroxysmal nocturnal hemoglobinuria and complement 3 glomerulopathy. Funded by the National Institute on Drug Abuse, Omeros’ lead phosphodiesterase 7 inhibitor OMS527 is in clinical development for the treatment of cocaine use disorder. Omeros also is advancing a broad portfolio of novel cellular and molecular immuno-oncology programs. For more information about Omeros and its programs, visit www.omeros.com.
