-- Greater than 16-Fold Improvement in
Survival Compared to Historical Control --
Omeros Corporation (NASDAQ: OMER) today announced new results
from the company’s ongoing Phase 2 study of OMS721 evaluating
patients with hematopoietic stem cell transplant-associated
thrombotic microangiopathy (HCT-TMA). The data demonstrate an
increase in median overall survival in HCT-TMA patients treated
with OMS721 compared to a matched historical control (347 days vs.
21 days, respectively, by Kaplan-Meier analysis; p < 0.0001 by
log-rank test). Historical control data are typically used for
comparison when it is impractical or unethical to include a placebo
arm in a clinical trial. In addition to and consistent with the
survival data reported today, updated assessments of platelet
count, lactate dehydrogenase (LDH) and haptoglobin – all markers of
TMA activity – continue to demonstrate clinically meaningful and
statistically significant improvements in the HCT-TMA patients
treated with OMS721.
A total of 19 HCT-TMA patients have been treated to date with
OMS721, 18 in the ongoing study and one patient under a
compassionate use protocol. An historical control that best matched
the OMS721-treated population was identified from the literature.
The literature reference selection criteria were those studies that
specified: (1) individual patient data (required for analysis), (2)
adult and/or adolescent populations, (3) allogeneic stem cell
transplant recipients only, and (4) no or partial response to
immunosuppressive regimen modification. Overall median survival
demonstrated greater than 16-fold improvement in survival in the
OMS721-treated group (p < 0.0001).
Markers of TMA activity in study participants, specifically mean
platelet count, mean LDH, and mean haptoglobin, continue to
demonstrate statistically and clinically significant improvements
following OMS721 treatment. At the end of protocol-allowed
treatment, the mean platelet count (normal range: 150,000 – 400,000
x 106/mL) increased from 18,100 x 106/mL at baseline to 52,300 x
106/mL (p = 0.017). The mean LDH (normal range: 125-220 U/L)
decreased from 591 U/L at baseline to 250 U/L (p < 0.001). The
mean haptoglobin (normal range: 14-268 mg/dL) increased from 8
mg/dL at baseline to 141 mg/dL (p = 0.003). Mean creatinine
remained stable at approximately 120 μmol/L (normal range: 63-104
μmol/L) but a majority of patients had co-existing conditions for
which they were receiving nephrotoxic medications. Other serious
co-existing conditions included graft versus host disease (GvHD),
cytomegalovirus and human herpes virus 6 infections, prior sepsis,
diffuse alveolar hemorrhage, and residual underlying
malignancies.
OMS721 has been well tolerated and no safety concerns have been
identified. The most commonly reported adverse events were diarrhea
and neutropenia. Four deaths occurred during the study: one due to
progression of acute myeloid leukemia, two due to neutropenic
sepsis, and one due to acute renal and respiratory failure. Only
one of these deaths – the acute renal and respiratory failure – was
considered “possibly drug-related” because an association could not
be definitively ruled out by the investigator. These are common
complications of HCT. The other three deaths were deemed not to be
related to OMS721.
Earlier data from this study have previously been presented at
the 2017 combined annual meetings of the Center for
International Blood & Marrow Transplant Research and
the American Society for Blood and Marrow Transplantation, the
2017 annual meeting of the European Society of Blood and Marrow
Transplantation (EBMT), and the 2017 EBMT Crash Course on Diagnosis
and Treatment of Noninfectious Complications after HCT. Two HCT-TMA
case reports were presented independently of Omeros at EBMT
meetings. One patient was an adolescent girl whose course was
complicated by diffuse alveolar hemorrhage (DAH) and who did not
tolerate eculizumab treatment but responded well to compassionate
use OMS721 treatment. She was able to discontinue all hemodialysis
as well as all platelet transfusions – prior to treatment with
OMS721, she was receiving hemodialysis thrice weekly platelet
transfusions. The second was a study patient who had a difficult
post-transplant course, including steroid-resistant GvHD and
cytomegalovirus infection. He developed TMA that did not respond to
conservative measures and had co-existing GvHD with multiple
neurological complications and was unable to walk. Following OMS721
treatment, his TMA and GvHD resolved and his neurological
complications improved. He was able to return to work and his
neurological status has continued to improve.
“As evidenced by the published literature, this is a population
with an extremely high mortality rate and a disorder for which
there is no approved therapy, and the improvement in survival in
these patients with OMS721 is compelling,” stated Rafael Duarte,
M.D., Ph.D., Associate Professor, Head of Hematopoietic
Transplantation and Hemato-oncology Section, University Hospital
Puerta de Hierro Majadahonda, Madrid Spain, and Secretary of the
European Society for Blood and Marrow Transplantation. “Thrombotic
microangiopathy following stem cell transplantation is increasingly
being recognized as part of a spectrum of endothelial cell injury
syndromes caused by the transplantation as well as by the
post-transplant medications and complications. These complications
include GvHD and diffuse alveolar hemorrhage. Seeing improvement in
overall survival and TMA markers combined with resolution of GvHD
and diffuse alveolar hemorrhage in critically ill patients
indicates the role that the lectin pathway plays in these syndromes
and the wide potential of OMS721 in stem cell transplantation.”
In the Phase 2 HCT-TMA clinical trial, patients receive weekly
OMS721 treatments for four or eight weeks, at the discretion of the
investigator. To be eligible for enrollment, HCT-TMA patients are
required to be adults with post-transplant TMA persisting at least
two weeks following immunosuppressive regimen modification
(conservative treatment) or more than 30 days post-transplant. This
population was chosen to represent a population at risk for poor
outcomes, including mortality. These patients often have severe
co-existing conditions, and mortality rates have been reported to
be as high as 100 percent.
“Hematopoietic stem cell transplantation is a potentially
curative and life-saving medical procedure but is far too often
complicated by thrombotic microangiopathy, for which serious cases
carry an unacceptably high mortality rate,” stated Gregory A.
Demopulos M.D., chairman and chief executive officer of Omeros.
“The improvement in overall survival in such a seriously ill
patient population is compelling. We look forward to working with
regulatory agencies to make our drug broadly available to
transplant patients as quickly as possible.”
Omeros is scheduled and expects to meet with the U.S. Food and
Drug Administration and with the European Medicines Agency to
discuss the most expeditious path to approval for OMS721 in
HCT-TMA.
About HCT-TMA
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.
About Graft-versus-Host 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.
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.
Phase 3 clinical programs are in progress for OMS721 in atypical
hemolytic uremic syndrome (aHUS), in immunoglobulin A (IgA)
nephropathy and in hematopoietic stem cell transplant-associated
thrombotic microangiopathy (HCT-TMA). Also, two Phase 2 trials are
ongoing. One is continuing to enroll IgA nephropathy patients and
has already generated positive data in patients with IgA
nephropathy and with lupus nephritis; the other is enrolling and
has reported positive data in patients with HCT-TMA and in patients
with aHUS. 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 thrombotic
microangiopathies 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 has initiated the manufacturing
scale-up process of its MASP-3 antibodies in preparation for
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 intraocular solution) 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 November
9, 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.
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version on businesswire.com: http://www.businesswire.com/news/home/20180215005588/en/
Cook Williams Communications, Inc.Jennifer Cook Williams,
360-668-3701Investor and Media Relationsjennifer@cwcomm.org
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