-- Pursuing Breakthrough Therapy Designation
in IgA Nephropathy (Berger’s Disease) --
Omeros Corporation (NASDAQ: OMER) today announced positive data
from the company’s Phase 2 clinical trial of OMS721 for the
treatment of kidney disorders, none of which currently have an
approved treatment and all of which frequently lead to end-stage
renal disease and dialysis. Statistical significance (p ≤ 0.017)
was achieved on key endpoints of improvement in renal function.
Omeros also reported the outcome of a recent FDA meeting regarding
breakthrough therapy designation for OMS721 in immunoglobulin A
(IgA) nephropathy (also known as Berger’s disease). Based on that
meeting, Omeros is pursuing FDA breakthrough therapy designation.
In addition to the Phase 2 program in renal diseases, OMS721 is
being evaluated in a Phase 3 program for patients with atypical
hemolytic uremic syndrome (aHUS) and in a Phase 2 program for
patients with thrombotic microangiopathies (TMAs), including
hematopoietic stem cell transplant-associated TMAs and thrombotic
thrombocytopenic purpura. OMS721 is Omeros’ lead human monoclonal
antibody targeting mannan-binding lectin-associated serine
protease-2 (MASP-2), the effector enzyme of the lectin pathway of
the complement system.
The Phase 2 open-label renal trial is evaluating OMS721 across
four different types of complement-associated kidney diseases: IgA
nephropathy (i.e., Berger’s disease), membranous nephropathy, lupus
nephritis, and complement component 3 (C3) glomerulopathy. Each of
the four renal-disease cohorts was planned to enroll four patients.
All patients in the trial must have high levels of urinary protein
(a marker used by nephrologists to assess disease activity) despite
ongoing treatment with a stable corticosteroid dose; these
inclusion criteria ensure that study patients are unlikely to
improve spontaneously. Patients are treated with OMS721 for a total
of 12 weeks: four weeks maintaining their entry corticosteroid
dose; four weeks of corticosteroid tapering, if tolerated; and four
weeks of resultant corticosteroid dose maintenance. Patients are
then followed post-treatment for six weeks. The key efficacy
measures are urine albumin-to-creatinine ratios (uACRs) throughout
the trial and change in 24-hour urine protein levels from baseline
to the end of treatment. To date, two patients with IgA
nephropathy, two patients with membranous nephropathy, and two
patients with lupus nephritis have completed the trial. Additional
patients have been enrolled and are being dosed.
The IgA nephropathy patients demonstrated a clinically
meaningful and statistically significant decrease in uACRs; lower
uACRs are associated with improved renal survival. Treatment
effects across the two patients were highly consistent. The mean
baseline uACR was 1264 mg/g and reached 525 mg/g at the end of
treatment (p = 0.011), decreasing to 128 mg/g at the end of the
follow-up period. Measures of 24-hour urine protein excretion
tracked uACRs, with a mean reduction from 3156 mg/day to 1119
mg/day (p = 0.017). Both patients experienced reductions of
approximately 2000 mg/day and both achieved a partial remission
(defined as greater than 50 percent reduction in 24-hour urine
protein excretion and/or resultant protein excretion less than 1000
mg/day; complete remission defined as protein excretion less than
300 mg/day). The magnitude of the 24-hour proteinuria reductions in
both IgA nephropathy patients is associated with significant
improvement in renal survival. Also, during the trial, daily
steroid doses for both patients were able to be reduced
substantially (60 mg to 0 mg and 30 mg to 5 mg).
The two patients with membranous nephropathy demonstrated
reductions in uACR during treatment. One patient had a decrease
from 1003 mg/g to 69 mg/g, maintaining this low level throughout
the follow-up period, while the other decreased from 1323 mg/g to
673 mg/g with a variable course after treatment. The first patient
showed a marked reduction in 24-hour urine protein excretion (10771
mg/day to 323 mg/day), achieving partial and nearly complete
remission, while the other remained essentially unchanged (4272
mg/day to 4502 mg/day). These combined effects did not reach
statistical significance. Daily steroid doses were able to be
tapered in the two patients from 10 mg to 5 mg and from 30 mg to 15
mg.
The time course of changes in uACR during treatment was
consistent across all four patients with IgA and membranous
nephropathies. Preliminary analysis demonstrated no evidence of
treatment effect in patients with lupus nephritis. No patients with
steroid-dependent C3 glomerulopathy, an extremely rare disorder,
have yet been enrolled. There is strong published evidence of
lectin pathway involvement in the pathophysiology of IgA
nephropathy and membranous nephropathy, with the evidence of lectin
pathway involvement weaker for lupus.
Consistent with the other clinical trials with OMS721, no
significant safety concerns have been observed. The most commonly
reported adverse events in this trial have been anemia and fatigue,
both commonly seen in these populations. Omeros plans to submit
these data for presentation at the European Renal
Association-European Dialysis Transplant Association 54th Annual
Congress to be held in June 2017.
Given the data seen in these renal patients, Omeros discussed
with the FDA’s Division of Cardiovascular and Renal Products the
potential treatment effects and the possibility of a rapid and
abbreviated path to approval. Based on the FDA’s guidance, Omeros
is pursuing breakthrough therapy designation for OMS721 in IgA
nephropathy and is amending the current protocol for its Phase 2
renal trial to assess five OMS721-treated and five placebo-treated
patients with the disease. These patients need not be
steroid-dependent, which is expected to greatly accelerate
enrollment. Achieving statistical significance is not required. In
parallel to completing the limited enrollment for breakthrough
designation, Omeros plans to advance OMS721 rapidly through its IgA
nephropathy development program to support both U.S. and
international marketing authorizations. After additional OMS721
data have been collected in membranous nephropathy patients, Omeros
may also pursue breakthrough therapy designation for that
indication.
No treatments are currently approved for either IgA nephropathy
or membranous nephropathy. IgA nephropathy is the most common
primary glomerular disease globally. With an annual incidence of
approximately 2.5 per 100,000, it is estimated that 1 in 1400
persons in the U.S. will develop IgA nephropathy. As many as 40
percent of them will develop end-stage renal disease. The annual
incidence of membranous nephropathy is approximately 10-12 per
1,000,000. Patients with membranous nephropathy can have a variable
clinical course, but approximately 25 percent will develop
end-stage renal disease.
“While the patient numbers are small, the consistency in the
patients’ clinical courses in these severe diseases is impressive,”
stated Professor Michal Nowicki, President of the Polish Society of
Nephrology and OMS721 clinical investigator. “The responses we have
observed in patients with aHUS, including reversal of renal failure
and dialysis cessation, and these renal data demonstrate the
potential of lectin pathway inhibition in nephrology.”
Omeros’ Phase 3 OMS721 aHUS program continues to progress with
Phase 3 enrollment planned to open late this year. The current TMA
Phase 2 clinical trial continues steadily to enroll and treat aHUS
patients, gathering data to support a biological license
application (BLA). Omeros plans to submit aHUS data from this study
for presentation at the International Society of Nephrology World
Congress of Nephrology in April 2017. The OMS721 program also
continues to support compassionate use in Europe and the FDA has
approved OMS721 for compassionate use in the U.S.
“We are very excited about these additional data in serious
renal diseases,” stated Gregory A. Demopulos M.D., chairman and
chief executive officer of Omeros. “The Phase 3 clinical trial for
aHUS is expected to open for enrollment later this year, and the
clinical data from these IgA and membranous nephropathy patients
increase the number of commercial avenues for OMS721. Current
understanding of the importance of the lectin pathway’s role across
inflammatory diseases is expanding, and we look forward to
continuing to work with the FDA and international regulatory
agencies to develop an efficient and rapid path to approval for
OMS721 in the treatment of aHUS, IgA and membranous nephropathies
and a number of other diseases.”
Additional data from Omeros’ OMS721 program are expected 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 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. Omeros has received both Orphan Drug status and Fast
Track designation from the U.S. FDA for its lead human MASP-2
antibody OMS721. Following discussions with both the FDA and the
European Medicines Agency, a Phase 3 program for OMS721 in atypical
hemolytic uremic syndrome is in progress. Also, two Phase 2 trials
are ongoing with one evaluating OMS721 in glomerulonephropathies,
which has generated positive data in patients with immunoglobulin A
(IgA) nephropathy and with membranous nephropathy, and the other in
thrombotic microangiopathies (TMAs), including hematopoietic stem
cell transplant-associated TMA and thrombotic thrombocytopenic
purpura. In addition to potential intravenous administration,
Omeros plans to commercialize OMS721 for one or more therapeutic
indications as a subcutaneous injection and is also 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.
Omeros also has identified MASP-3 as the protein that is
critical to the activation of 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 its development of antibodies
and small-molecule inhibitors against MASP-3 to 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. Part of its proprietary PharmacoSurgery® platform,
the company’s first drug product, OMIDRIA® (phenylephrine and
ketorolac injection) 1%/0.3%, was broadly launched in the U.S. in
April 2015. OMIDRIA is the first and only FDA-approved drug (1) 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 and (2) that
contains an NSAID for intraocular use. In the European Union, the
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 clinical-stage
development programs focused on: complement-related thrombotic
microangiopathies; complement-mediated glomerulonephropathies;
Huntington’s disease and cognitive impairment; and addictive and
compulsive disorders. In addition, Omeros has a proprietary G
protein-coupled receptor (GPCR) platform, which is making available
an unprecedented number of new GPCR drug targets and corresponding
compounds to the pharmaceutical industry for drug development, and
a platform used to generate antibodies.
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, 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 9, 2016. 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/20161017005473/en/
Cook Williams Communications, Inc.Jennifer Cook WilliamsInvestor
and Media Relations360-668-3701jennifer@cwcomm.org
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