-- Results May Expand Target for Omeros’ Planned Phase 3 Program
in HCT-TMA --
SEATTLE--(BUSINESS WIRE)--Oct. 20, 2017--
Omeros Corporation (NASDAQ: OMER) today 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.
About Omeros’ MASP Programs
Omeros controls the worldwide rights to MASP-2 and all therapeutics
targeting MASP-2, a novel pro-inflammatory protein target involved in
activation of the complement system, which is an important component of
the immune system. The complement system plays a role in the
inflammatory response and becomes activated as a result of tissue damage
or microbial infection. MASP-2 is the effector enzyme of the lectin
pathway, one of the principal complement activation pathways.
Importantly, inhibition of MASP-2 does not appear to interfere with the
antibody-dependent classical complement activation pathway, which is a
critical component of the acquired immune response to infection, and its
abnormal function is associated with a wide range of autoimmune
disorders. MASP-2 is generated by the liver and is then released into
circulation. Adult humans who are genetically deficient in one of the
proteins that activate MASP-2 do not appear to be detrimentally affected
by the deficiency. OMS721 is Omeros’ lead human MASP-2 antibody.
Following discussions with both the FDA and the European Medicines
Agency, a Phase 3 clinical program for OMS721 in atypical hemolytic
uremic syndrome (aHUS) is in progress. A second Phase 3 clinical program
for OMS721 has been initiated in immunoglobulin A (IgA) nephropathy.
Also, two Phase 2 trials are ongoing. One is continuing to enroll OMS721
in IgA nephropathy following an earlier Phase 2 trial that generated
positive data in patients with IgA nephropathy and with lupus nephritis;
the other is enrolling and has reported positive data both in patients
with hematopoietic stem cell transplant-associated thrombotic
microangiopathy (TMA). A third Phase 3 program could begin later this
year in stem cell transplant-associated TMA. OMS721 can be administered
both intravenously and subcutaneously, and Omeros expects to
commercialize each formulation of OMS721 for different therapeutic
indications. In parallel, Omeros is developing small-molecule inhibitors
of MASP-2. Based on requests from treating physicians, Omeros has
established a compassionate-use program for OMS721, which is active in
both the U.S. and Europe. The FDA has granted OMS721 breakthrough
therapy designation for IgA nephropathy, orphan drug status for the
prevention (inhibition) of complement-mediated TMAs and for the
treatment of IgA nephropathy, and fast track designation for the
treatment of patients with aHUS.
Omeros also has identified MASP-3 as responsible for the conversion of
pro-factor D to factor D and as a critical activator of the human
complement system’s alternative pathway. The alternative pathway is
linked to a wide range of immune-related disorders. In addition to its
lectin pathway inhibitors, the company is advancing its development of
antibodies and small-molecule inhibitors against MASP-3 to block
activation of the alternative pathway. Omeros is preparing to initiate
manufacturing scale-up of its MASP-3 antibodies in advance of clinical
trials.
About Omeros Corporation
Omeros is a commercial-stage biopharmaceutical company committed to
discovering, developing and commercializing small-molecule and protein
therapeutics for large-market as well as orphan indications targeting
inflammation, complement-mediated diseases and disorders of the central
nervous system. The company’s drug product OMIDRIA®
(phenylephrine and ketorolac injection) 1% / 0.3% is marketed for use
during cataract surgery or intraocular lens (IOL) replacement to
maintain pupil size by preventing intraoperative miosis (pupil
constriction) and to reduce postoperative ocular pain. In the European
Union, the European Commission has approved OMIDRIA for use in cataract
surgery and other IOL replacement procedures to maintain mydriasis
(pupil dilation), prevent miosis (pupil constriction), and to reduce
postoperative eye pain. Omeros has multiple Phase 3 and Phase 2
clinical-stage development programs focused on: complement-associated
thrombotic microangiopathies; complement-mediated
glomerulonephropathies; Huntington’s disease and cognitive impairment;
and addictive and compulsive disorders. In addition, Omeros has a
diverse group of preclinical programs and a proprietary G
protein-coupled receptor (GPCR) platform through which it controls 54
new GPCR drug targets and corresponding compounds, a number of which are
in preclinical development. The company also exclusively possesses a
novel antibody-generating platform.
Forward-Looking Statements
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
Securities and Exchange Commission on August 8, 2017. Given these risks,
uncertainties and other factors, you should not place undue reliance on
these forward-looking statements, and the company assumes no obligation
to update these forward-looking statements, even if new information
becomes available in the future.
View source version on businesswire.com: http://www.businesswire.com/news/home/20171020005289/en/
Source: Omeros Corporation
Cook Williams Communications, Inc.
Jennifer Cook Williams
Investor
and Media Relations
360-668-3701
jennifer@cwcomm.org