-- Magnitude of Proteinuria Reduction Consistent With Previous Cohort
--
SEATTLE--(BUSINESS WIRE)--Oct. 1, 2018--
Omeros Corporation (NASDAQ: OMER) today announced positive data from the
company’s ongoing Phase 2 clinical trial of OMS721 for the treatment of
renal diseases. The data are from study patients with immunoglobulin A
(IgA) nephropathy, a progressively worsening kidney disease and the most
common glomerulonephritis worldwide, responsible for 10 percent of all
people on dialysis globally. Patients in this cohort had IgA nephropathy
with high risk of progression but none received corticosteroid treatment
immediately prior to or during the study – different than the cohort
reported last year in which all patients initiated the study while on
steroid therapy. Reductions in protein levels in urine collected over a
24-hour duration (the “gold-standard” in assessing proteinuria) in this
steroid-free OMS721-treated group were of similarly large magnitude to
those seen in the earlier cohort. In IgA nephropathy, proteinuria is the
most reliable prognostic factor for loss of kidney function – the
greater the proteinuria reduction, the better the prognosis. OMS721 is
Omeros’ lead human monoclonal antibody targeting mannan-binding
lectin-associated serine protease-2 (MASP-2), the effector enzyme of the
complement system’s lectin pathway. In addition to an ongoing Phase 3
clinical trial in IgA nephropathy, OMS721 is in Phase 3 clinical
programs for hematopoietic stem cell-associated thrombotic
microangiopathy (HSCT-TMA) and for atypical hemolytic uremic syndrome.
OMS721 has been granted breakthrough therapy designations by FDA for
both IgA nephropathy and HSCT-TMA.
“We now have results of treatment with OMS721 in IgA nephropathy
patients both with and without concomitant steroid therapy,” stated
Jonathan Barratt, Professor of Renal Medicine at the University of
Leicester and Honorary Consultant Nephrologist at Leicester General
Hospital. “In contrast to the previously reported cohort who were
enrolled while on steroid therapy, the patients in this study were
steroid-free, and yet the magnitude of proteinuria reduction across both
groups is consistent and likely to indicate a significant renoprotective
effect of OMS721 in IgAN, with a legacy effect again seen for months
beyond cessation of OMS721 treatment. Notably, the current study’s
patients are at very high risk of progressive renal disease and
generally have long-standing, established disease with multiple
comorbidities, representing a difficult-to-treat population. Despite
that, almost all of the OMS721-treated patients responded to the first
12-week course of treatment. Collectively, these data further confirm
the rationale for lectin pathway inhibition as a promising future option
for the treatment of patients with IgAN.”
The current cohort study was designed to evaluate the safety and
tolerability of once-weekly intravenous (IV) dosing of OMS721 and to
describe the effect of the drug on 24-hour proteinuria in patients with
IgA nephropathy. Twelve patients were enrolled. Per protocol, patients
are required (i) to not receive corticosteroids during the study
duration or for at least three months prior to screening and (ii) to be
stable on an optimized dose of ACE inhibitors/ARBs (i.e.,
renin-angiotensin system [RAS] blockade) before enrollment. In a
double-blind design, study patients were randomized 1:1 to receive
either OMS721 or placebo for 12 weeks, and then both groups could
receive extended OMS721 dosing at investigator discretion. Three
patients were excluded from the analysis: two for unstable RAS blockade
with at least a 50 percent change in dosing of RAS-blockade medication
during the study, and one for untreated gastrointestinal disease that
persisted throughout a substantial majority of the study duration. These
conditions are known to affect proteinuria levels markedly, and results
from these patients were determined by IgA nephropathy expert review to
be unevaluable.
For the nine evaluable patients, median reductions in proteinuria
following the initial 12-week course of treatment were 18.4 percent and
18.0 percent for the OMS721 and placebo groups, respectively. The one
OMS721-treated patient whose proteinuria level remained elevated after
the initial treatment course subsequently reached a 67.8-percent
reduction from baseline following an additional course of OMS721 dosing.
After the initial 12-week treatment with OMS721 or placebo, all patients
rolled into a dosing-extension period during which time a patient could
receive, at investigator discretion, treatment with OMS721 if his/her
respective 24-hour proteinuria level remained above 1 gram or the
proteinuria response was less than a 50-percent reduction from baseline.
Eight patients received OMS721 in this extension period, after either
first receiving 12 weeks of OMS721 or placebo. Comparison with baseline
of the proteinuria data after at least 18 weeks in the study (i.e.,
after the first course of OMS721 or placebo treatment and six-week
follow-up) shows a median proteinuria reduction for this group of 55.7
percent. Four patients in this OMS721 dosing-extension period have
reached between 9 and 12 months beyond baseline, and show reductions in
proteinuria of 53.9 percent, 57.4 percent, 65.3 percent, and 67.8
percent. At most recent assessment, two of these four patients have
continued to demonstrate sustained reductions in proteinuria for 2.5 and
5 months, respectively, after cessation of treatment with OMS721; the
other two patients just recently completed treatment courses.
For the evaluable patients in the OMS721-treated and placebo groups,
respectively, median ages at study start were 50 vs 33 years old; median
time since diagnosis was 19 vs 9 years; and median baseline proteinuria
was 2.9 vs 2.5 g/day. Forty-four percent of these patients had
nephrotic-range proteinuria at baseline, ranging from approximately 4.5
to 12 g/day, and most patients had multiple comorbidities.
Consistent with all other studies conducted with OMS721, the drug was
well tolerated and no safety concerns were seen in this cohort of
patients. Across all 12 patients, no treatment-related serious adverse
events were observed, and most reported adverse events were mild or
moderate.
The OMS721 treatment-extension period in this cohort study remains
ongoing. Omeros plans to report additional data from this Phase 2 cohort
at a future medical congress.
“We’re pleased with the strength of the data across a relatively small
cohort of predominantly high-proteinuria patients and with the magnitude
of the effect on proteinuria in the absence of steroid exposure,” stated
Gregory A. Demopulos, M.D., chairman and chief executive officer
of Omeros. “Given these results, we are exploring ways to streamline our
active Phase 3 development program in IgA nephropathy. In addition,
while most IgA nephropathy patients treated with OMS721 have responded
rapidly to a single course of dosing, this study has demonstrated the
potential benefit provided by limited multi-course dosing of the drug.
Our ongoing Phase 3 ARTEMIS-IGAN trial incorporates repeat-dosing
regimens to take advantage of this opportunity.”
No treatments are approved for IgA nephropathy. With an annual incidence
of approximately 1 per 100,000, it is estimated that 1 in 1,400 persons
in the U.S. will develop IgA nephropathy in his or her lifetime. As many
as 40 percent of them will develop end-stage renal disease.
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 (HSCT-TMA). Also, two Phase 2 trials are ongoing. One is
continuing to evaluate IgA nephropathy patients and has generated
positive data in two cohorts of patients with IgA nephropathy (with and
without concurrent corticosteroid therapy, respectively) and with lupus
nephritis; the other is enrolling and has reported positive data in
patients with HSCT-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 and for high-risk HSCT-TMA,
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 plans for its MASP-3
program to enter the clinic late next year.
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; 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,” “exploring”, “goal,” “intend,” “likely,”
“look forward to,” “may,” “plan,” “potential,” “predict,” “promising”,
“project,” “prospects,” “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 9, 2018. 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,
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Investor and Media Relations
jennifer@cwcomm.org