Omeros Corporation has launched site activation for its Phase 3 clinical trial program evaluating zaltenibart in paroxysmal nocturnal hemoglobinuria (PNH), with many sites already identifying eligible patients ready to participate. The company remains on track to collect the necessary data for biologics licensing application (BLA) submission by the fourth quarter of 2026.
The Phase 3 program will evaluate zaltenibart (OMS906), Omeros' investigational MASP-3 inhibitor that targets the alternative pathway of complement. The drug has shown promise in addressing both intravascular hemolysis (treated by current C5 inhibitors) and extravascular hemolysis (caused by C5 inhibitors) in PNH patients.
Significant Dosing Advantage
A key differentiator for zaltenibart is its dosing regimen. The Phase 3 trials will evaluate intravenous administration once every eight weeks, offering a substantial convenience improvement over currently marketed treatments that require either twice-daily oral dosing, thrice-daily oral dosing with C5 inhibitor treatment, or twice-weekly subcutaneous infusions.
"The zaltenibart Phase 2 data have demonstrated important differentiators from currently marketed agents, and we expect those same advantages to be evidenced in the Phase 3 trials," said Gregory A. Demopulos, M.D., Omeros' Chairman and CEO. "We continue to refine and optimize the potential commercial impact of the zaltenibart advantages, and we look forward to our Phase 3 readout late next year."
Comprehensive Clinical Trial Design
The Phase 3 program consists of two clinical trials:
- A study in patients not currently receiving complement-inhibitor treatment
- A study in patients showing inadequate response to ravulizumab or eculizumab
Both trials will compare zaltenibart monotherapy against C5 inhibitors eculizumab and ravulizumab, with designs approved by both FDA and European regulators. The head-to-head comparisons aim to demonstrate superiority of zaltenibart, potentially supporting comparative claims for promotion, enhanced market access, and premium pricing.
Omeros has already manufactured all zaltenibart drug product required for the Phase 3 program and secured the comparator C5 inhibitors.
Promising Phase 2 Results
Previous Phase 2 data presented at major hematology conferences demonstrated zaltenibart's effectiveness in inhibiting both intravascular and extravascular hemolysis while achieving gender-normal hemoglobin levels in both men and women. No significant safety concerns have been observed with the treatment.
The company has also incorporated patient-reported-outcome measures into the Phase 3 design based on recommendations from the German Federal Joint Committee, which should support appropriate pricing strategies upon potential commercialization.
Market Potential and Future Indications
The global market for PNH treatments was reported at $3.8 billion in 2023 and is projected to grow to over $11.7 billion by 2034, representing a significant commercial opportunity for Omeros.
Beyond PNH, Omeros is currently conducting a Phase 2 clinical trial of zaltenibart for C3 glomerulopathy and is evaluating additional indications related to the alternative pathway for future clinical trials.
Mechanism of Action
Zaltenibart targets mannan-binding lectin-associated serine protease-3 (MASP-3), the key activator of the complement system's alternative pathway. Unlike C5 and C3 blockers, MASP-3 inhibition preserves the lytic arm of the classical pathway, which is important for fighting infections.
MASP-3 is believed to be an ideal target in the alternative pathway due to its low native circulating level and low relative clearance compared to other alternative pathway proteins. Additionally, MASP-3 is not thought to be an acute phase reactant, potentially giving zaltenibart an advantage over other alternative pathway inhibitors.
The company believes MASP-3 inhibitors like zaltenibart may have therapeutic potential across a broad range of diseases beyond PNH, including hemolytic uremic syndrome, traumatic brain injury, arthritis, geographic atrophy, and transplant-related complications.
