Omeros' (OMER) OMS721 Phase 2 Trial Achieves Key Endpoints

October 17, 2016 7:11 AM EDT

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Omeros Corporation (NASDAQ: OMER) today announced positive data from the company’s Phase 2 clinical trial of OMS721 for the treatment of kidney disorders, none of which currently have an approved treatment and all of which frequently lead to end-stage renal disease and dialysis. Statistical significance (p ≤ 0.017) was achieved on key endpoints of improvement in renal function. Omeros also reported the outcome of a recent FDA meeting regarding breakthrough therapy designation for OMS721 in immunoglobulin A (IgA) nephropathy (also known as Berger’s disease). Based on that meeting, Omeros is pursuing FDA breakthrough therapy designation. In addition to the Phase 2 program in renal diseases, OMS721 is being evaluated in a Phase 3 program for patients with atypical hemolytic uremic syndrome (aHUS) and in a Phase 2 program for patients with thrombotic microangiopathies (TMAs), including hematopoietic stem cell transplant-associated TMAs and thrombotic thrombocytopenic purpura. OMS721 is Omeros’ lead human monoclonal antibody targeting mannan-binding lectin-associated serine protease-2 (MASP-2), the effector enzyme of the lectin pathway of the complement system.

The Phase 2 open-label renal trial is evaluating OMS721 across four different types of complement-associated kidney diseases: IgA nephropathy (i.e., Berger’s disease), membranous nephropathy, lupus nephritis, and complement component 3 (C3) glomerulopathy. Each of the four renal-disease cohorts was planned to enroll four patients. All patients in the trial must have high levels of urinary protein (a marker used by nephrologists to assess disease activity) despite ongoing treatment with a stable corticosteroid dose; these inclusion criteria ensure that study patients are unlikely to improve spontaneously. Patients are treated with OMS721 for a total of 12 weeks: four weeks maintaining their entry corticosteroid dose; four weeks of corticosteroid tapering, if tolerated; and four weeks of resultant corticosteroid dose maintenance. Patients are then followed post-treatment for six weeks. The key efficacy measures are urine albumin-to-creatinine ratios (uACRs) throughout the trial and change in 24-hour urine protein levels from baseline to the end of treatment. To date, two patients with IgA nephropathy, two patients with membranous nephropathy, and two patients with lupus nephritis have completed the trial. Additional patients have been enrolled and are being dosed.

The IgA nephropathy patients demonstrated a clinically meaningful and statistically significant decrease in uACRs; lower uACRs are associated with improved renal survival. Treatment effects across the two patients were highly consistent. The mean baseline uACR was 1264 mg/g and reached 525 mg/g at the end of treatment (p = 0.011), decreasing to 128 mg/g at the end of the follow-up period. Measures of 24-hour urine protein excretion tracked uACRs, with a mean reduction from 3156 mg/day to 1119 mg/day (p = 0.017). Both patients experienced reductions of approximately 2000 mg/day and both achieved a partial remission (defined as greater than 50 percent reduction in 24-hour urine protein excretion and/or resultant protein excretion less than 1000 mg/day; complete remission defined as protein excretion less than 300 mg/day). The magnitude of the 24-hour proteinuria reductions in both IgA nephropathy patients is associated with significant improvement in renal survival. Also, during the trial, daily steroid doses for both patients were able to be reduced substantially (60 mg to 0 mg and 30 mg to 5 mg).

The two patients with membranous nephropathy demonstrated reductions in uACR during treatment. One patient had a decrease from 1003 mg/g to 69 mg/g, maintaining this low level throughout the follow-up period, while the other decreased from 1323 mg/g to 673 mg/g with a variable course after treatment. The first patient showed a marked reduction in 24-hour urine protein excretion (10771 mg/day to 323 mg/day), achieving partial and nearly complete remission, while the other remained essentially unchanged (4272 mg/day to 4502 mg/day). These combined effects did not reach statistical significance. Daily steroid doses were able to be tapered in the two patients from 10 mg to 5 mg and from 30 mg to 15 mg.

The time course of changes in uACR during treatment was consistent across all four patients with IgA and membranous nephropathies. Preliminary analysis demonstrated no evidence of treatment effect in patients with lupus nephritis. No patients with steroid-dependent C3 glomerulopathy, an extremely rare disorder, have yet been enrolled. There is strong published evidence of lectin pathway involvement in the pathophysiology of IgA nephropathy and membranous nephropathy, with the evidence of lectin pathway involvement weaker for lupus.

Consistent with the other clinical trials with OMS721, no significant safety concerns have been observed. The most commonly reported adverse events in this trial have been anemia and fatigue, both commonly seen in these populations. Omeros plans to submit these data for presentation at the European Renal Association-European Dialysis Transplant Association 54th Annual Congress to be held in June 2017.

Given the data seen in these renal patients, Omeros discussed with the FDA’s Division of Cardiovascular and Renal Products the potential treatment effects and the possibility of a rapid and abbreviated path to approval. Based on the FDA’s guidance, Omeros is pursuing breakthrough therapy designation for OMS721 in IgA nephropathy and is amending the current protocol for its Phase 2 renal trial to assess five OMS721-treated and five placebo-treated patients with the disease. These patients need not be steroid-dependent, which is expected to greatly accelerate enrollment. Achieving statistical significance is not required. In parallel to completing the limited enrollment for breakthrough designation, Omeros plans to advance OMS721 rapidly through its IgA nephropathy development program to support both U.S. and international marketing authorizations. After additional OMS721 data have been collected in membranous nephropathy patients, Omeros may also pursue breakthrough therapy designation for that indication.

No treatments are currently approved for either IgA nephropathy or membranous nephropathy. IgA nephropathy is the most common primary glomerular disease globally. With an annual incidence of approximately 2.5 per 100,000, it is estimated that 1 in 1400 persons in the U.S. will develop IgA nephropathy. As many as 40 percent of them will develop end-stage renal disease. The annual incidence of membranous nephropathy is approximately 10-12 per 1,000,000. Patients with membranous nephropathy can have a variable clinical course, but approximately 25 percent will develop end-stage renal disease.

“While the patient numbers are small, the consistency in the patients’ clinical courses in these severe diseases is impressive,” stated Professor Michal Nowicki, President of the Polish Society of Nephrology and OMS721 clinical investigator. “The responses we have observed in patients with aHUS, including reversal of renal failure and dialysis cessation, and these renal data demonstrate the potential of lectin pathway inhibition in nephrology.”

Omeros’ Phase 3 OMS721 aHUS program continues to progress with Phase 3 enrollment planned to open late this year. The current TMA Phase 2 clinical trial continues steadily to enroll and treat aHUS patients, gathering data to support a biological license application (BLA). Omeros plans to submit aHUS data from this study for presentation at the International Society of Nephrology World Congress of Nephrology in April 2017. The OMS721 program also continues to support compassionate use in Europe and the FDA has approved OMS721 for compassionate use in the U.S.

“We are very excited about these additional data in serious renal diseases,” stated Gregory A. Demopulos M.D., chairman and chief executive officer of Omeros. “The Phase 3 clinical trial for aHUS is expected to open for enrollment later this year, and the clinical data from these IgA and membranous nephropathy patients increase the number of commercial avenues for OMS721. Current understanding of the importance of the lectin pathway’s role across inflammatory diseases is expanding, and we look forward to continuing to work with the FDA and international regulatory agencies to develop an efficient and rapid path to approval for OMS721 in the treatment of aHUS, IgA and membranous nephropathies and a number of other diseases.”

Additional data from Omeros’ OMS721 program are expected later this year.

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