Omeros announced that it has reached agreement with the FDA on Omeros’ protocol for its phase 3 clinical trial evaluating OMS721 in patients with IgA nephropathy (IgAN). Patient enrollment is expected to begin early next month.
The single phase 3 trial is a randomized, double-blind, placebo-controlled trial in patients at least 18 years of age with biopsy-confirmed IgAN and with 24-hour urine protein excretion greater than 1 g/day at baseline on optimized renin-angiotensin system (RAS) blockade. Patients will receive an initial 12 weekly intravenous doses of study drug; additional weekly dosing can be administered for partial responders and relapsers. The primary endpoint, which could suffice for full approval, is reduction in proteinuria at 24 weeks after the start of dosing. The trial will employ an adaptive design that will allow intra-trial adjustment in sample size. For purposes of safety and efficacy assessments, the initial sample size for the proteinuria endpoint is estimated at 140 patients in each of the treatment and placebo groups. This will include a subset of patients with high levels of proteinuria (i.e., equal to or greater than 2 g/day) at baseline, and full approval could also be obtained if a substantial improvement is seen at 24 weeks in this subset of patients alone. The trial design will allow assessment for either full or accelerated approval at 24 weeks based on proteinuria results either (1) across the general population of study patients or (2) in the high-proteinuria subset of patients. In the event that the primary endpoint at 24 weeks results in accelerated approval from FDA, change in estimated glomerular filtration rate (eGFR) will be assessed at approximately 3 years after the start of dosing. The initial sample size estimate for the eGFR endpoint is approximately 160 patients per group and also will be adjustable under the study’s adaptive design.
FDA granted both breakthrough therapy designation and orphan drug designation for OMS721 in IgAN. Omeros’ applications to the European Medicines Agency (EMA) for orphan drug status and for eligibility to the Priority Medicines (PRIME) program for OMS721 in IgAN are pending.
Omeros has also initiated its phase 3 program for OMS721 in hematopoietic stem cell-associated thrombotic microangiopathy (HCT-TMA) and intends to amend the ongoing phase 2 protocol following discussion with FDA and/or EMA to transition the protocol into a phase 3/pivotal trial. In the third quarter of 2017, Omeros submitted a preliminary breakthrough therapy designation request to FDA for OMS721 in HCT-TMA. Based on the data in that submission, FDA requested that Omeros submit a full application for breakthrough therapy designation for OMS721 in HCT-TMA following collection of additional information on the patients in the phase 2 clinical trial. Omeros intends to submit the full application for breakthrough therapy designation by the end of this month. Enrollment in the phase 2 trial has continued pending initiation of/conversion to the pivotal trial. Omeros also recently applied for eligibility to EMA’s PRIME program for OMS721 in HCT-TMA. FDA has already granted orphan designation for OMS721 in the prevention (inhibition) of complement-mediated TMAs, which includes HCT-TMA.
The company’s phase 3 program in aHUS is also ongoing in both the US and Europe. The single-arm, open label, phase 3 trial is targeting approximately 40 patients for EMA approval and US accelerated approval with 80 patients required for full approval in the US. Dosing consists of an initial IV loading followed by daily subcutaneous dosing. The FDA has granted OMS721 fast track designation in aHUS as well as orphan designation for OMS721 in aHUS and other complement-mediated TMAs.
“We’re pleased to have received agreement from FDA for our OMS721 phase 3 protocol in IgA nephropathy,” Gregory A. Demopulos, MD, chairman and chief executive officer of Omeros, said in a company news release. “Final preparations to begin the trial can now be completed and enrollment is expected to open in early February. To our OMS721 phase 3 programs in IgA nephropathy and aHUS, we have recently added a third phase 3 program in stem cell transplant-associated TMA. We look forward to ongoing discussions with both FDA and EMA regarding the HCT-TMA phase 3 trial as well as breakthrough and PRIME designations. In the meantime, enrollment in the phase 2 HCT-TMA trial has progressed with patients expected to have a very high mortality rate doing well on OMS721.”