Omeros launches Phase 3 program of zaltenibart as PNH treatment
2 clinical trials across 30 countries to test therapy's safety, efficacy
Clinical site activation is now ongoing for a Phase 3 program that will evaluate zaltenibart (OMS906) as a treatment for people with paroxysmal nocturnal hemoglobinuria (PNH), its developer Omeros has announced.
A total of 120 sites across 30 countries were chosen for clinical trial participation, according to a company press release, which noted that investigators at “a good number of” these sites have already identified eligible and available patients to enroll. Two Phase 3 trials — with different patient criteria — will assess zaltenibart’s safety and efficacy when given intravenously, or directly into the bloodstream, once every eight weeks.
Data, which the company expects to support its submission of a biologics licensing application seeking zaltenibart’s approval for PNH, is expected by the end of 2026, per the release.
“All of us at Omeros are pleased that the Phase 3 clinical program for zaltenibart is well underway,” said Gregory A. Demopulos, MD, the company’s chairman and CEO. “We look forward to our Phase 3 readout late next year and to bringing a better treatment option to PNH patients and their physicians.”
Zaltenibart designed to work differently than approved PNH treatments
In PNH, the complement system — a component of the immune system that normally helps fight off infections — starts attacking and destroying healthy blood cells, particularly red blood cells. This leads to anemia and other disease symptoms, including fatigue, dizziness, and shortness of breath.
All of the medications approved to treat PNH to date work to block complement activation to prevent red blood cell destruction, known medically as hemolysis. However, in doing so, they also increase a person’s risk of infection.
Zaltenibart is an antibody-based therapy that’s designed to block MASP-3, a protein that is a key activator of the alternative complement pathway. By specifically blocking this branch of the complement system and leaving others unaffected, zaltenibart is expected to stop hemolysis occurring both inside and outside blood vessels, without compromising the body’s ability to fight off infections.
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.
The therapy was found to be well tolerated in healthy volunteers and to consistently block MASP-3 in a Phase 1 trial. Additionally, in a proof-of-concept Phase 1b study (NCT05889299), which enrolled 10 adults with PNH and severe anemia who had never been treated with a complement inhibitor, monthly doses of zaltenibart (5 mg/kg) were shown to normalize markers of hemolysis.
A Phase 2 trial (NCT05972967) then tested the therapy in PNH patients who had failed to respond to the approved treatment Ultomiris (ravulizumab). Those results demonstrated that zaltenibart effectively stopped hemolysis occurring inside and outside blood vessels and also normalized hemoglobin levels in both men and women. Hemoglobin is the oxygen-carrying protein inside red blood cells.
Further, no safety concerns were observed in the trial, according to Omeros.
“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, which are similar in design to our Phase 2 trials,” Demopulos said.
The two trials in zaltenibart’s Phase 3 program target different patient populations. One will enroll individuals who are not receiving treatment with complement inhibitors at the time of study entry. The other will recruit patients who responded inadequately to either Ultomiris or Soliris (eculizumab); both of these approved complement inhibitors work by targeting a protein called C5.
Both clinical trials will compare the efficacy and safety of zaltenibart as a standalone therapy to that of Soliris and Ultomiris.
Regulatory agencies in both the U.S. and Europe have agreed with the trial designs. According to Omeros, the trials will test whether or not zaltenibart is superior to C5 inhibitors in these patient populations.
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