SEATTLE, Aug. 18, 2015 /PRNewswire/ -- Omeros Corporation
(NASDAQ: OMER) today announced additional positive data in the
company's Phase 2 clinical trial of OMS721 for the treatment of
thrombotic microangiopathies (TMAs). TMAs are a family of rare,
debilitating and life-threatening disorders characterized by
excessive thrombi (clots) – aggregations of platelets –
in the microcirculation of the body's organs, most commonly the
kidney and brain. OMS721 is Omeros' lead human monoclonal antibody
in its mannan-binding lectin-associated serine protease-2 (MASP-2)
program for the treatment of TMAs, including atypical hemolytic
uremic syndrome (aHUS).
The Phase 2 trial is designed to enroll primarily aHUS patients
but can also enroll patients with thrombotic thrombocytopenic
purpura (TTP) and hematopoietic stem cell transplant (HSCT)-related
TMA. The trial has fully enrolled the first and second cohorts and
is currently completing the third and final planned cohort of its
dose-ranging stage. In each three-patient cohort, OMS721 is dosed
for four weeks. Data from the first (low-dose) cohort were released
on February 19, 2015. Today the
company is releasing data from its second (mid-dose) cohort and
data to date from its third (high-dose) cohort.
Three patients were treated in the second or mid-dose cohort,
two of whom have aHUS and one with TTP. Both patients with aHUS
were on renal dialysis prior to and at the time of study
enrollment. Based on the positive data from the mid-dose cohort,
the high-dose cohort was initiated and an aHUS patient has already
completed the study treatment period. No patient with HSCT-related
TMA has yet completed dosing with OMS721. The data referenced for
all patients include measures to one week following the last
dose.
A rare and devastating family of disorders, TMAs are
characterized by thrombi or clumps of aggregated platelets in small
blood vessels, which lead to thrombocytopenia (below-normal
platelet counts) and schistocytes (fragmentation in red blood
cells) that can cause dangerously low oxygen levels in organs like
the brain and kidney as well as anemia. Thrombotic
microangiopathies are life-threatening and can occur both in
children and adults. While thrombi, thrombocytopenia and
schistocytes are hallmarks of TMAs, other markers of damage within
the blood vessels include an elevated plasma lactate dehydrogenase
(LDH) and undetectable or reduced plasma haptoglobin levels. In
addition, an elevated creatinine level – a result of the
kidney damage caused by thrombi – is an indicator of impaired
kidney function in patients who are not on renal dialysis.
As in Alexion's clinical trials supporting both U.S. and
European regulatory approval of Soliris® for the
treatment of aHUS, this Phase 2 clinical trial, given the
life-threatening nature of the disease, has no placebo arm. Soliris
trials used change from baseline in platelet count as a primary
endpoint to obtain approval for the treatment of aHUS. Similarly,
the pre-specified primary endpoint in this Phase 2 trial is change
from baseline in platelet count. In this trial, platelet counts in
all three aHUS patients in the mid- and high-dose cohorts (two in
the mid-dose and one in the high-dose cohort) were normal after the
treatment period, with a statistically significant mean increase
from baseline of approximately 68,000 platelets/mL (p =
0.0055).
In the mid-dose cohort, the two patients with plasma
therapy-resistant aHUS demonstrated:
- 47% increase in mean platelet count, resulting in both patients
having counts in the normal range
- 86% decrease in mean schistocyte count, with schistocytes
disappearing in one patient
- 71% increase in mean haptoglobin with both patients reaching
the normal range during treatment, one slipping slightly below
normal at one week following the last dose
- 5% decrease in the mean levels of LDH, with levels in both
patients remaining slightly elevated above normal range
The mid-dose-cohort patient with TTP required repeated plasma
infusion therapy prior to entering the study. Laboratory parameters
did not show consistent improvement, but the patient did not
require plasma therapy during treatment with OMS721 and, to date,
has not required it since completing treatment.
The first patient in the high-dose cohort – a plasma
therapy-resistant aHUS patient with additional complicating
disorders including hepatitis C, cryoglobulinemia and lymphoma –
has also completed treatment with OMS721. Prior to OMS721
treatment, the patient required repeated dialysis. Throughout
treatment and following completion of the OMS721 course, the
patient to date has remained off dialysis. Hematological and renal
parameters showed:
- 63% improvement in platelet count, returning to normal
levels
- 100% decrease in schistocytes
- Haptoglobin increased from an undetectable level and
normalized
- 43% decrease in LDH, resulting in a level just slightly above
normal
- 24% reduction in creatinine level
As expected, patients with aHUS in the mid- and high-dose
cohorts demonstrated more consistent and robust improvement in
efficacy measures than patients in the low-dose cohort. As in the
low-dose cohort, the drug was well tolerated by all patients in the
mid- and high-dose cohorts throughout the treatment period.
There have been no confirmed clinically meaningful drug-related
adverse events in any clinical trials with OMS721. To date, two
clinically meaningful adverse events were considered possibly
related to OMS721 when first observed because an infectious
etiology could not be ruled out at diagnosis, but all cultures
subsequently proved negative. Specifically, one patient in the
low-dose cohort was reported as possibly having an infection (as
described in the company's February 19,
2015 press release); however, all cultures were negative and
no infection was identified. Another patient had significant
diarrhea, but all tests for gastrointestinal pathogens were
negative and the patient was receiving immunosuppressive therapy,
including a drug very commonly associated with diarrhea. In
addition, animal chronic toxicity studies have been completed and
no notable adverse findings were observed. The FDA has cleared
OMS721 for chronic dosing in clinical trials. Physician-requested
compassionate use is ongoing, and all patients in the
compassionate-use program are reported by their physicians to be
doing well.
"We are excited by the data from this Phase 2 clinical trial
with OMS721, both with respect to aHUS and TTP patients," stated
Gregory A. Demopulos M.D., chairman
and chief executive officer of Omeros. "Based on clinical data, we
expect that we can deliver OMS721 either subcutaneously or
intravenously at a frequency and dose that are both convenient and
comfortable for patients while effectively eliminating
lectin-pathway activity. Compassionate use in aHUS patients has
begun, and we look forward to advancing to the fixed-dose
stage of the trial and discussing Phase 3 trial design with
the FDA later this year."
About Omeros' MASP-2 Program
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 appears to
be unique to, and required for the function of, one of the
principal complement activation pathways, known as the lectin
pathway. 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 the 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. Omeros has received both Orphan Drug status and
Fast Track designation from the U.S. FDA for its lead human MASP-2
antibody OMS721. An ongoing Phase 2 clinical program is evaluating
OMS721 in the treatment of thrombotic microangiopathies (TMAs),
including atypical hemolytic uremic syndrome, thrombotic
thrombocytopenic purpura and stem cell transplant-related TMAs. An
investigator-requested compassionate use program for OMS721 is also
underway. Chronic toxicity studies with systemically delivered
OMS721 demonstrated no drug-related adverse events and, in addition
to potential intravenous administration, Omeros plans to
commercialize OMS721 for one or more therapeutic indications as a
subcutaneous injection.
Omeros also believes that it has identified the proteins that
activate the complement system's alternative pathway in humans,
which is linked to a wide range of immune-related disorders. In
addition to its lectin pathway inhibitors, the Company is advancing
the development of antibodies that block activation of the
alternative pathway.
About Omeros Corporation
Omeros is a biopharmaceutical company committed to discovering,
developing and commercializing both small-molecule and protein
therapeutics for large-market as well as orphan indications
targeting inflammation, coagulopathies and disorders of the central
nervous system. Derived from its proprietary
PharmacoSurgery® platform, the company's first drug
product, Omidria® (phenylephrine and ketorolac
injection) 1%/0.3%, has been approved by the FDA 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,
European Commission has approved Omidria for use in cataract
surgery and lens replacement procedures to maintain mydriasis
(pupil dilation), prevent miosis (pupil constriction), and to
reduce postoperative eye pain. Omeros has partnered its
arthroscopic product, OMS103, for commercialization with Fagron
Sterile Services and affiliated JCB Laboratories. Omeros has five
clinical-stage development programs focused on: complement-related
thrombotic microangiopathies; Huntington's disease, schizophrenia,
and cognitive impairment; addictive and compulsive disorders; and
preventing problems associated with urologic surgical procedures.
In addition, Omeros has a proprietary GPCR platform, which is
making available an unprecedented number of new GPCR drug targets
and corresponding compounds to the pharmaceutical industry for drug
development.
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. 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
including with respect to Omidria® and OMS103, Omeros'
ability to partner and commercialize Omidria in Europe, Omeros' 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 10, 2015. 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.
To view the original version on PR Newswire,
visit:http://www.prnewswire.com/news-releases/omeros-announces-additional-positive-data-in-oms721-phase-2-clinical-trial-300129793.html
SOURCE Omeros Corporation