Omeros Corporation (NASDAQ:OMER) announced the presentation of a case report of a patient having co-existing hematopoietic stem cell transplant-associated thrombotic microangiopathy (HCT-TMA) and graft-versus-host disease (GvHD), which both resolved following OMS721 treatment. This case was presented this morning at the European Society for Blood and Marrow Transplantation (EBMT) Crash Course on Diagnosis and Treatment of Noninfectious Complications after HCT in Granada, Spain. The presentation, “Effective Treatment of GvHD-Associated Transplant-Associated Microangiopathy with a Novel Inhibitor of the Lectin Pathway of Complement,” was made by Chiara Caprioli, M.D. of the Hematology and Bone Marrow Transplant Unit, Azienda Ospedaliera Papa Giovanni XXIII, in Bergamo, Italy.
The patient was a participant in Omeros’ ongoing Phase 2 uncontrolled clinical trial of thrombotic microangiopathies, including HCT-TMA. To be eligible for enrollment, HCT-TMA patients are required to be adults with post-transplant TMA persisting at least two weeks following calcineurin inhibitor modification (conservative treatment). This population is considered to be at high risk for poor outcomes, including mortality.
Prior to enrollment in the OMS721 trial, the patient had undergone HCT for T-cell acute lymphoblastic leukemia. His post-transplant course was complicated by multiple episodes of steroid-refractory grade IV (life-threatening) GvHD, cytomegalovirus infection, and HCT-TMA. After two prior episodes of GvHD, the patient presented with bloody diarrhea. Intestinal biopsy demonstrated both HCT-TMA and GvHD. No infections were identified. Notably, the patient also had new onset neurological symptoms of paresthesias, tetraparesis, and a neurogenic bladder, which have been reported as neurological manifestations of GvHD and TMA. The patient was unable to walk due to the tetraparesis and required blood transfusions at least once daily. Hematological markers demonstrated HCT-TMA with thrombocytopenia, elevated lactate dehydrogenase (LDH), and schistocytes. Two weeks prior to initiation of treatment with OMS721, his immunosuppression (cyclosporine) had been decreased and, given his history of steroid-refractory GvHD, he was receiving only low-dose corticosteroids. He received no other GvHD treatment.
After two OMS721 doses, his bloody diarrhea resolved and his hematological markers improved. After four OMS721 doses, he was able to walk with help. He completed eight weeks of OMS721 treatment and has been doing well at home. All signs and symptoms of HCT-TMA and all clinical symptoms of GvHD have resolved. His neurological symptoms have continued to improve.
“This patient’s marked response to OMS721 treatment was very gratifying,” stated Anna Grassi, M.D., Director of the Bone Marrow Transplant Unit at the Azienda Ospedaliera Papa Giovanni XXIII. “The cause of his neurological symptoms is not clear, but may be a manifestation of GvHD or other endothelial injury. Prior to OMS721 treatment, this patient was deteriorating and at high risk for early death. The improvement of GvHD, HCT-TMA, and the neurological symptoms following OMS721 treatment is promising.”
“This case reinforces recent thinking that endothelial injury is a common cause of post-transplant complications in our patients,” stated Professor Alessandro Rambaldi, Director of Department of Hematology and Oncology, Azienda Ospedaliera Papa Giovanni XXIII. “This patient’s course suggests that inhibition of the lectin pathway may be beneficial in the treatment of HCT-complicating endothelial syndromes beyond TMA, including GvHD. I look forward to further study of this pathway and treatment.”
Thrombotic microangiopathy is a potentially life-threatening complication of HCT. Approximately 20,000 HCT procedures are performed in the U.S. annually, and TMA is reported to occur in approximately 10 to 25 percent of HCT patients. Although the kidney is the most commonly affected organ, HCT-TMA is a multi-system disorder and can also manifest clinically in the lungs, gastrointestinal tract and central nervous system. Reported mortality in patients with multi-organ involvement is greater than 90%. Even in patients who survive acute episodes, HCT-TMA increases the risk for chronic kidney disease and end-stage renal disease.
Graft-versus-host disease is a common complication of HCT. Both acute and chronic forms exist and result from donor immune cells recognizing the recipient patient as foreign tissue. This triggers an immune response against the recipient patient. Acute GvHD occurs in up to 50% or more of patients who receive allogeneic transplants. Acute GvHD most commonly targets the skin, gastrointestinal tract, and liver, but can also affect the kidney, eye, lung, and blood cells. Chronic GvHD occurs in approximately 40% of patients who receive allogeneic transplants and most commonly affects the skin, liver, eye, gastrointestinal tract and lungs. Both acute and chronic GvHD are related to significant morbidity and mortality.
The most frequently reported adverse events in HCT patients treated with OMS721 have been nausea and diarrhea, neither of which investigators have deemed “drug-related.” One possibly treatment-related serious adverse event has been reported because the investigator could not rule out a contribution from OMS721. This patient was neutropenic, developed sepsis and subsequently died. Neutropenic sepsis is a common complication of HCT. Other infection-related deaths have occurred in the trial at times when the patients were not receiving OMS721 treatment (i.e., in the screening or follow-up periods).
“Our OMS721 clinical trials continue to yield exciting data,” stated Gregory A. Demopulos M.D., chairman and chief executive officer of Omeros. “Potential treatment of both HCT-TMA and GvHD is consistent with our understanding of lectin pathway activation in the setting of endothelial injury. We continue to treat patients with OMS721 who have a high likelihood of mortality and the results to date have been impressive. We plan to initiate later this year a Phase 3 program in HCT-TMA and will discuss with regulators approaches to expand the program to assess GvHD as well.”
In addition to its clinical program in HCT-TMA, OMS721 is being evaluated in Phase 3 clinical programs for atypical hemolytic uremic syndrome and for immunoglobulin A nephropathy (IgAN). OMS721 has received breakthrough therapy designation from FDA for IgAN and Omeros is in discussions with FDA for breakthrough designation for the drug in HCT-TMA. Omeros also is applying for the European Medicines Agency’s Priority Medicines (PRIME) program for OMS721 in each of IgAN and HCT-TMA.
Shares of Omeros are up nearly 3% to $19.70 in pre-market trading Friday. OMER has a 1-year high of $27.09 and a 1-year low of $7.80. The stock’s 50-day moving average is $20.85 and its 200-day moving average is $19.47.
On the ratings front, Omeros has been the subject of a number of recent research reports. In a report issued on August 24, Cantor analyst Elemer Piros reiterated a Hold rating on OMER. On August 11, Needham’s Serge Belanger reiterated a Buy rating on the stock and has a price target of $28.
According to TipRanks.com, which ranks over 7,500 financial analysts and bloggers to gauge the performance of their past recommendations, Elemer Piros and Serge Belanger have a yearly average return of 5.6% and 4.2% respectively. Piros has a success rate of 52% and is ranked #1146 out of 4698 analysts, while Belanger has a success rate of 41% and is ranked #1802.
Omeros 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.