Report of Successful OMS721 Treatment of Patient with Both Stem Cell Transplant-Associated Thrombotic Microangiopathy and Graft-versus-Host Disease Presented at EBMT Annual Meeting
-- Results May Expand Target for Omeros’ Planned Phase 3 Program in HCT-TMA --
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
“This case reinforces recent thinking that endothelial injury is a
common cause of post-transplant complications in our patients,” stated
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
About Omeros’ MASP Programs
Following discussions with both the
This press release contains forward-looking statements within the
meaning of Section 27A of the Securities Act of 1933 and Section 21E of
the Securities Exchange Act of 1934, which are subject to the “safe
harbor” created by those sections for such statements. All statements
other than statements of historical fact are forward-looking statements,
which are often indicated by terms such as “anticipate,” “believe,”
“could,” “estimate,” “expect,” “goal,” “intend,” “look forward to,”
“may,” “plan,” “potential,” “predict,” “project,” “should,” “will,”
“would” and similar expressions and variations thereof. Forward-looking
statements are based on management’s beliefs and assumptions and on
information available to management only as of the date of this press
release. Omeros’ actual results could differ materially from those
anticipated in these forward-looking statements for many reasons,
including, without limitation, risks associated with product
commercialization and commercial operations, unproven preclinical and
clinical development activities, regulatory oversight, intellectual
property claims, competitive developments, litigation, and the risks,
uncertainties and other factors described under the heading “Risk
Factors” in the company’s Quarterly Report on Form 10-Q filed with the
Cook Williams Communications, Inc.
Jennifer Cook Williams
Investor and Media Relations