Omeros has finalized its clinical plan for OMS721 submission and approval in immunoglobulin A nephropathy (IgAN) following a recent meeting with the U.S. Food and Drug Administration (FDA). OMS721 is Omeros’ lead human monoclonal antibody targeting MASP-2, the effector enzyme of the complement system’s lectin pathway. There is no approved treatment for IgA nephropathy.
Clinical results from the first and second cohorts of the Phase 2 trial in IgAN were part of the background materials provided to FDA for the recent meeting on the Phase 3 clinical program. During the FDA meeting, the following points were confirmed:
- The Phase 3 trial’s primary endpoint of assessment of proteinuria was extended from 24 to 36 weeks at the company’s request to allow for additional OMS721 dosing, if needed. This continues to provide OMS721 a path to accelerated, or even full, approval based on those 36-week proteinuria data in either (i) the entire patient population (patients with baseline proteinuria greater than 1 gm/24 hours) or (ii) the high-risk subpopulation (those with baseline proteinuria of at least 2 gm/24 hours).
- Given investigators’ concerns about extended withholding of OMS721 treatment from any high-risk study patient initially randomized to the placebo-treated group, patients in that subpopulation will be allowed open-label treatment with OMS721 after at least 1 year of blinded treatment.
The OMS721 Phase 3 ARTEMIS-IGAN trial continues to enroll and will incorporate the beneficial changes noted above without any impact to study patients already enrolled. The trial is designed based on the positive results from the two previously reported Phase 2 cohorts – the first assessing patients who were receiving corticosteroids at time of enrollment and then tapered off steroids during the study and the second comprised of patients who were not taking steroids.
Additional Phase 2 Data
Additional data are available from patients in the second cohort of the Phase 2 trial who entered the extended follow-up period, all receiving OMS721 treatment during this period. The 8 patients in the extended follow-up period had longstanding IgA nephropathy (median time from diagnosis of 11.6 years) with significant comorbidities and significantly impaired renal function (median baseline estimated glomerular filtration rate (eGFR) of 35.7 mL/min/1.73 m2) with highly elevated baseline proteinuria levels (median of 3,786 mg/24 hours). The data, based on the last observation point for each patient, confirm the positive results seen earlier:
- eGFR measurements have remained stable, consistent with preservation of renal function
- 61 percent median reduction in proteinuria from baseline (across all 8 patients, assessed at 31 weeks to 54 weeks post-baseline)
- 5 of the 8 patients have achieved greater than 50 percent proteinuria reductions (median reduction of 65 percent), with 2 of those 5 having received their last OMS721 administration 5 months earlier
- Across the first (4 patients) and second cohorts, a total of 9 of 12 patients achieved greater than 50 percent reductions in proteinuria (median reduction of 65 percent)
- OMS721 continues to be well tolerated and no safety concerns have been observed
"The data from the Phase 2 study continue to show a consistent and significant drug effect, the magnitude of which is unparalleled," stated Richard Lafayette, MD, Professor of Medicine (Nephrology) and Director of the Glomerular Disease Center, Stanford University Medical Center and chair of the OMS721 IgAN Academic Leadership Committee. "Nephrologists are focused on long-term kidney survival, and the observed effects of OMS721 on both proteinuria and eGFR are what we would hope to see in an IgAN treatment. The OMS721 Academic Leadership Committee believes the data on OMS721 in IgAN are sufficiently groundbreaking and robust to warrant publication in a major scientific journal and plans to submit the Phase 2 data for publication in the first half of this year, together with other publications directed to OMS721 in renal disease throughout 2019. From the perspective of the ALC, the extended data from the Phase 2 cohort study strongly support the potential efficacy of OMS721 in IgA nephropathy, even in patients at the very highest risk of progression to kid...
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