-- Greater than 16-Fold Improvement in Survival Compared to
Historical Control --
SEATTLE--(BUSINESS WIRE)--Feb. 15, 2018--
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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Source: Omeros Corporation
Cook Williams Communications, Inc.
Jennifer Cook Williams,
360-668-3701
Investor and Media Relations
jennifer@cwcomm.org