Omeros Corporation (NASDAQ:OMER) announced additional positive data from the company’s Phase 2 clinical trial of OMS721 for the treatment of serious kidney disorders, which frequently lead to end-stage renal disease and dialysis. OMS721 is Omeros’ lead human monoclonal antibody targeting mannan-binding lectin-associated serine protease-2 (MASP-2), the effector enzyme of the complement system’s lectin pathway. The clinical trial data include results from additional study patients treated with OMS721 as well as longer-term follow-up on earlier enrolled patients. The new data corroborate and expand on trial results reported in the fourth quarter of 2016. Based on the uniformly positive data in the fully enrolled cohort of OMS721-treated patients with immunoglobulin A nephropathy (IgAN), Omeros recently met with the FDA to discuss the Phase 3 development program.
“The clinical responses in my IgA nephropathy patients treated with OMS721 are truly impressive,” stated Geoffrey Block, M.D., Director of Clinical Research at Denver Nephrology. “These are patients with significant renal impairment who had not responded to steroid therapy. Each OMS721-treated patient substantially improved while markedly reducing or stopping steroid use. Equally impressive is that, after OMS721 treatment was completed, a legacy effect of continued improvement was observed in each patient. I look forward to participating in the Phase 3 clinical trial and to working with Omeros to make this important drug broadly available to patients.”
The Phase 2 open-label trial is evaluating OMS721 across four different types of complement-associated kidney diseases: IgAN, membranous nephropathy, lupus nephritis, and complement component 3 (C3) glomerulopathy. To meet enrollment criteria, patients must have high levels of urinary protein (a marker used by nephrologists to assess disease activity) despite well-controlled blood pressure with stable dosing of renin-angiotensin system inhibitors and ongoing treatment with a corticosteroid, thereby ensuring 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 trial assesses the effect of OMS721 on urine protein measures that are predictive of kidney failure, namely urine albumin/creatinine ratio (uACR) and total 24-hour urine protein excretion, and on the ability to reduce steroid dosing. Data were analyzed for the pre-specified IgAN cohort of four patients (three have completed treatment in the study and the fourth is finishing treatment).
Treatment effects across all IgAN patients were highly consistent, the magnitude of which are associated with improved renal survival. Notably, uACR values continued to improve after dosing was completed. In the three patients who completed treatment, the mean baseline uACR was 1,400 mg/g and reached 671 mg/g at the end of treatment (52 percent decrease; p = 0.02), continuing to decrease to 380 mg/g by the end of the follow-up period. Measures of 24-hour urine protein excretion tracked uACRs, with a mean reduction from 3,728 mg/day to 1,340 mg/day (64 percent decrease; p = 0.02). To date, after eight weeks of treatment, the fourth patient’s uACR dropped from 1,628 mg/g to 733 mg/g, a decrease of 55 percent. Partial remission is defined as greater than 50 percent reduction in 24-hour urine protein excretion. In the patients who completed treatment, 24-hour urine protein levels decreased by approximately 50 to 80 percent. Concurrently, daily steroid doses for all patients were substantially reduced or completely eliminated.
“The OMS721 data in IgAN patients demonstrate a strength and rapidity of clinical response that I have not seen with other agents in development,” said Jonathan Barratt, Ph.D., F.R.C.P., Professor of Renal Medicine in the Department of Infection, Immunity & Inflammation at University of Leicester and Honorary Consultant Nephrologist at Leicester General Hospital. “There currently is no approved therapy for IgA nephropathy. The mechanism of IgA nephropathy – and proteinuria in general – has been closely linked to the lectin pathway of complement, and OMS721 directly targets the pathway’s effector enzyme MASP-2. This could uniquely position OMS721 not only for the treatment of IgA nephropathy but for a host of other kidney disorders as well.”
Encouraging results have also been observed in lupus nephritis. Four of five patients showed a substantial (mean of 69 percent) reduction in 24-hour urine protein excretion over the treatment period. The fifth patient experienced a systemic disease flare and showed a substantial increase. The majority of lupus responders were able to taper their steroid doses. Three patients with membranous nephropathy, a disease with inherent variability, have completed treatment with mixed results. Additional analyses are continuing in these patient groups.
Consistent with all other OMS721 clinical trials, no significant safety concerns have been observed. The most commonly reported adverse events in this trial are fatigue and anemia.
Omeros met with FDA recently to discuss these data and Phase 3 development. Following review of the data, FDA suggested that Omeros apply for breakthrough therapy designation in IgAN. The discussion included accelerated approval and an expedited approach to full approval based on an endpoint of proteinuria, which could be faster than accelerated approval. Omeros is preparing its breakthrough application and a Phase 3 protocol for discussion with FDA. The Phase 3 trial in IgAN is expected to begin this year.
“We’re pleased with the consistently positive data seen in IgAN patients, further expanding the strong OMS721 clinical results beyond those previously reported in aHUS and stem-cell transplant patients,” stated Gregory A. Demopulos, M.D., chairman and chief executive officer of Omeros. “We are submitting our breakthrough therapy application to FDA and look forward to working closely with U.S. and international regulators as we advance through our Phase 3 clinical programs across multiple indications for OMS721.”
No treatments are approved for IgAN, an orphan disease but the most common primary glomerular disease globally. With an annual incidence of approximately 1 per 100,000, it is estimated that 1 in 1,400 persons in the U.S. will develop IgAN in his or her lifetime. As many as 40 percent of them will develop end-stage renal disease.
Shares of Omeros are up nearly 7% to $15.50 in pre-market trading Thursday. OMER has a 1-year high of $16.40 and a 1-year low of $7.20. The stock’s 50-day moving average is $11.64 and its 200-day moving average is $10.58.
On the ratings front, Omeros has been the subject of a number of recent research reports. In a report issued on March 28, Maxim analyst Jason Kolbert reiterated a Buy rating on OMER, with a price target of $22, which implies an upside of 51% from current levels. Separately, on March 20, Wedbush’s Liana Moussatos reiterated a Buy rating on the stock and has a price target of $47.
According to TipRanks.com, which ranks over 7,500 financial analysts and bloggers to gauge the performance of their past recommendations, Jason Kolbert and Liana Moussatos have a yearly average loss of -10.7% and a return of 11.3% respectively. Kolbert has a success rate of 33% and is ranked #4489 out of 4555 analysts, while Moussatos has a success rate of 45% and is ranked #373.
Sentiment on the street is mostly bullish on OMER stock. Out of 4 analysts who cover the stock, 4 suggest a Buy rating . The 12-month average price target assigned to the stock is $47, which implies an upside of 223% from current levels.
Omeros Corp. operates as a biopharmaceutical company committed to discovering, developing, and commercializing small-molecule and protein therapeutics for large-market as well as orphan indications targeting inflammation, coagulopathies, and disorders of the central nervous system.