OMS906 normalizing markers of hemolysis in Phase 1b clinical trial

Study data at 5 months of treatment show better hemoglobin, other key levels

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by Steve Bryson PhD |

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Treatment with OMS906 is showing an ability to normalize all markers of red blood cell destruction, or hemolysis, in severely anemic people with paroxysmal nocturnal hemoglobinuria (PNH) never given a complement inhibitor.

According to a five-month interim analysis of a Phase 1b proof-of-concept study (NCT05889299), once monthly, under-the-skin (subcutaneous) injections of the experimental therapy improved the levels of hemoglobin, lactate dehydrogenase, and reticulocytes. No trial patient required a blood transfusion.

“Our Phase 2 clinical asset, OMS906, continues to deliver data consistent with a premier drug targeting the premier enzyme in the alternative pathway, increasing confidence in our objective to make OMS906 the first-line, standard-of-care for a wide range of alternative pathway disorders,” Gregory A. Demopulos, MD, chairman and CEO of Omeros, the therapy’s developer, said in a company financial report.

Interim study data were presented at the recent 2023 Congress of the European Hematology Association in a talk titled, “OMS906, a Mannan-Binding Lectin-Associated Serine Protease-3 (MASP-3) Inhibitor, Normalizes Hemoglobin Levels in Treatment-Naïve PNH Patients: Interim Data From a Proof-of-Concept Clinical Trial.”

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A potentially safer paroxysmal nocturnal hemoglobinuria treatment

Most cases of PNH are caused by mutations in the PIGA gene in hematopoietic stem cells, which can give rise to new blood cells. Such mutations render blood cells, especially red blood cells that carry oxygen through the body, vulnerable to attacks by the complement system — a group of proteins that normally help protect against infection.

Resulting red blood cell destruction leads to anemia and other hallmark disease symptoms, including fatigue, blood in the urine, and shortness of breath.

Approved PNH therapies all work by blocking steps in complement activation to stop hemolysis, but in so doing they can increase a person’s susceptibility to infections.

OMS906 blocks a specific branch of the complement system — the so-called alternative complement pathway — by targeting a protein called MASP-3. This is thought to help stop hemolysis while preserving the part of the complement system that’s responsible for defending the body against infections.

Normal hemoglobin levels seen in 8 of 9 patients with two or more treatments

An earlier Phase 1 study in healthy volunteers showed that OMS906 was well tolerated and capable of sustained MASP-3 inhibition.

In the ongoing Phase 1b trial, 10 adults with paroxysmal nocturnal hemoglobinuria are being treated with low monthly doses of OMS906 (5 mg/kg). As of an interim analysis cutoff date of May 29, nine of these patients had received two or more doses, and three received six doses.

Participants had a number of co-existing conditions, including iron deficiency, chronic kidney failure, aplastic anemia (a bone marrow disorder), and myelodysplastic syndrome (a rare type of cancer affecting immature blood cells in bone marrow).

Before treatment (baseline measures), their mean blood level of hemoglobin was 7.1 grams per deciliter (g/dL) — considerably below the minimum normal range of 12 g/dL. Of note, hemoglobin is the oxygen-carrying protein in red blood cells.

The mean level of lactate dehydrogenase (LDH), a marker of cell damage, was 1,828 units per liter (U/L), far above the normal range of 140 to 280 U/L. Counts of reticulocytes, or immature red blood cells, also were elevated at 175 x 109/L.

As previously reported, the mean hemoglobin level rose to 12.4 g/dL — nearly doubling baseline measures — after 85 days and three subcutaneous injections of OMS906 at low dose.

In this interim analysis, with data covering up to day 141 of treatment, the eight patients without myelodysplastic syndrome reached gender-normal hemoglobin levels.

All 10 patients had an increase in hemoglobin levels of 2 g/dL or more, and the eight without myelodysplastic syndrome saw their hemoglobin levels rise to at least 12 g/dL.

No blood transfusions were required following OMS906 treatment, and no breakthrough hemolysis episodes were reported.

LDH levels fell by 1,916 U/L from baseline to reach a normal range, while reticulocyte counts dropped by 106 x 109/L.

Reasonable safety being shown with OMS906’s use

OMS906 was well tolerated, with no concerning safety signals reported. Adverse events occurring in 20% or more of the patients included headache, itching, low platelet counts, and low immune neutrophil cell counts.

Researchers noted that those with reported low platelets or neutrophils had evidence of underlying bone marrow failure. No serious adverse events or trial discontinuations were reported.

Omeros is also evaluating OMS906 in PNH patients who failed to respond to treatment with the approved PNH therapy Ultomiris (ravulizumab) in an ongoing Phase 2 trial (NCT05972967). Seven of its expected 12 adult patients have been enrolled at sites in Europe, with additional patients undergoing screening.

The candidate therapy, at 3 or 5 mg/kg, will be given in combination with Ultomiris once every eight weeks for about six months. OMS906 then will be administered alone in those who demonstrate a hemoglobin response with the combination therapy, while others may continue on both treatments or standard of care.