OMS721 demonstrates activity in thrombotic microangiopathies

The human monoclonal antibody OMS721 appeared effective for the treatment of patients with thrombotic microangiopathies, according to results of a phase 2 trial released by the agent’s manufacturer.

OMS721 (Omeros Corporation) conferred benefits in three patients in a mid-dose cohort, as well as one patient in a high-dose cohort.

Thrombotic microangiopathies are rare, life-threatening conditions in which excessive clots form in the microcirculation of the organs, most often the brain and kidney, according to a press release issued by Omeros.

The phase 2 trial is designed to evaluate OMS721 in patients with atypical hemolytic uremic syndrome (aHUS), as well as thrombotic thrombocytopenic purpura (TTP) and hematopoietic stem cell transplant-related thrombotic microangiopathies.

The company released data from a low-dose trial cohort in February.

New data from the mid-dose cohort showed two patients with plasma therapy-resistant aHUS achieved a 47% increase in mean platelet count, an 86% decrease in mean schistocyte count, a 71% increase in mean haptoglobin and a 5% decrease in mean levels of lactate dehydrogenase.

Platelet counts returned to normal range in both patients and schistocytes disappeared in one patient. Mean haptoglobin reached the normal range in both patients during treatment but slipped below normal in one patient 1 week after the final dose. LDH levels remained slightly above normal in both patients following treatment.

The mid-dose cohort also included a third patient with TTP who required repeated plasma infusion therapy before study enrollment. Although laboratory parameters did not suggest consistent improvement, the patient did not require plasma therapy during or after treatment.

Omeros also released data from one patient in a high-dose cohort who had plasma therapy-resistant aHUS and multiple other complicating conditions, including lymphoma, cryoglobulinemia and hepatitis C.

The patient required repeated dialysis prior to study enrollment. However, the patient remained off dialysis during and after treatment with OMS721.

Results indicated the treatment conferred a 63% improvement in platelet count, resulting in a return to normal level; a 100% decrease in schistocytes; a 43% decline in lactate dehydrogenase level, stabilizing at a level slightly elevated from normal; and a 24% decrease in creatinine clearance. The patient’s haptoglobin, which had been at an undetectable level, normalized after treatment.

Company officials said there have been no confirmed clinically meaningful drug-related adverse events in any OMS721 trials.

“We are excited by the data from this phase 2 clinical trial with OMS721, both with respect to aHUS and TTP patients,” Gregory A. Demopulos MD, chairman and CEO of Omeros, said in a press release. “Based on clinical data, we expect that we can deliver OMS721 either subcutaneously or intravenously at a frequency and dose that are both convenient and comfortable for patients while effectively eliminating lectin-pathway activity. Compassionate use in aHUS patients has begun, and we look forward to advancing to the fixed-dose stage of the trial and discussing phase 3 trial design with the FDA later this year.”