Omeros has completed dosing of the low-dose cohort of patients in its ongoing phase II clinical trial evaluating the efficacy and safety of OMS721, the lead human monoclonal antibody for its mannan-binding lectin-associated serine protease-2 (MASP-2) program, in treating thrombotic microangiopathies (TMAs). TMAs are a family of rare, debilitating and life-threatening disorders characterized by excessive thrombi (clots) in the microcirculation of the body's organs, most commonly the kidney and brain.
All patients in this study cohort received OMS721 and improvements were observed across TMA disease markers. The investigators treating all of these patients at different sites consider the improvements to be treatment-related and clinically meaningful. Based on observations in this cohort, a European investigator has requested that Omeros provide extended access to OMS721 for compassionate use in his two study patients, both of whom suffer from atypical hemolytic uremic syndrome (aHUS), a form of TMA.
In the clinical trial, the first cohort consisted of three patients treated with the lowest dose of OMS721. All three patients have aHUS. Platelet count, serum lactate dehydrogenase (LDH) and serum haptoglobin were measured as markers of disease activity. When compared to baseline levels, platelet counts improved in all patients. Serum LDH levels remained normal in one patient, substantially decreased to close to the normal range in another and remained elevated in the third. Haptoglobin improved in two patients, normalizing in one. Creatinine levels in the one patient with independent renal function also improved.
Under the program of extended access, the two patients treated by the investigator requesting compassionate use will continue to undergo current or higher dosing with OMS721. The third patient, treated at a site other than that of the requesting investigator, appeared clinically to no longer be in the acute phase of the disease after treatment with OMS721. The patient subsequently relapsed following cessation of OMS721 treatment.
This patient was discontinued from the trial for precautionary reasons because of a serious adverse event—a localized inflammatory response often related to certain types of infections, one of which the patient previously had for three years while on immunosuppressive therapy. Such infections are associated with widely used TNF-alpha-targeting drugs. All data to date indicate no active infection in this patient.
No other significant safety issues were observed in either this trial or in the previously completed phase I program. Consistent with the phase II trial protocol, a pre-planned data review by internal and external physicians resulted in a recommendation to proceed with the planned dose escalation to the mid-dose cohort.
Omeros has agreed to provide the requested access to OMS721 for compassionate use, subject to approval from the applicable European regulatory authority, which has indicated its interest in facilitating the request. Notification of the investigator's request for extended access was posted on ClinicalTrials.gov.