XOMA 052 Clinical Results Support Novel Anti-Inflammatory Approach to Type 2
Diabetes Treatment
BERKELEY, Calif., June 6, 2009 (GLOBE NEWSWIRE) -- XOMA Ltd. (Nasdaq:XOMA), a
leader in the discovery and development of therapeutic antibodies, announced new
results which included additional data for up to three months and new measures
of biological activity from Phase 1 clinical trials of a single dose of XOMA 052
given intravenously to patients with Type 2 diabetes. The new results provide
further confirmation of the potential for XOMA 052 as an entirely new
anti-inflammatory approach to the treatment of Type 2 diabetes. The results were
presented at the American Diabetes Association (ADA) 69th Scientific Sessions in
New Orleans, Louisiana by Marc Y. Donath, M.D., a pioneer in anti-inflammatory
approaches to Type 2 diabetes, Professor at the University Hospital of Zurich
and XOMA 052 European clinical trial principal investigator.
XOMA 052 is designed to address the inflammatory cause of Type 2 diabetes by
targeting IL-1 beta, a master signaling protein which triggers inflammatory
pathways in the body, which in diabetes results in reduced insulin production in
pancreatic beta cells. By targeting the inflammatory component of Type 2
diabetes, XOMA 052 has the potential to be a novel, disease-modifying treatment
for Type 2 diabetes.
The biological activity results presented at the ADA meeting included data from
39 Type 2 diabetes patients for which combined data were available in the U.S.
and Switzerland. A total of 30 patients were randomized to receive a single I.V.
dose of XOMA 052 at 0.01, 0.03 or 0.1 milligrams per kilogram of body weight
(mg/kg), and nine patients received placebo. The U.S. patients were followed for
approximately two months and the Swiss patients were followed for three months.
Additional data were collected at the Swiss site including insulin and glucose
measures during the oral glucose tolerance test (oGTT) and the glucose arginine
glucagon (GAG) tests, and whole blood cytokine assays.
A summary of the results follows. Additional data can be found in the Detailed
Results section below. Slides from the ADA presentation will be available on the
company's website, www.xoma.com.
The studies demonstrated:
* XOMA 052 was well-tolerated, with no drug or dose-related
serious adverse events or injection site reactions.
* Improvement in insulin production and secretion for patients
receiving XOMA 052 for as long as 91 days.
* A durable reduction of high sensitivity C-Reactive Protein
(hsCRP), a standard measure of inflammation which is
associated with an increased risk of cardiovascular events,
for as long as 91 days following a single infusion of
XOMA 052.
* Consistent reduction in glycosylated hemoglobin(HbA1c), a
standard measure of average glucose control over a
three-month period for XOMA 052-treated patients as compared
to placebo for as long as 91 days.
* A favorable immunologic profile, with XOMA 052 having
positive effects on reducing the levels of pro-inflammatory
cytokines such as TNF-alpha, IL-6 and IL-1alpha. In addition,
XOMA 052 did not demonstrate a suppressive effect on
protective cytokines including interferon-alpha and IL-1
receptor antagonist, which are needed for infection control
and host defense.
* A pharmacokinetic profile, including a 22 day half-life,
which suggests the potential for XOMA 052 dosing at monthly
or less frequent intervals.
"It is well-recognized that IL-1 beta levels are up-regulated in response to
elevated glucose. This causes an auto-inflammatory process in insulin-producing
cells that can lead to their death and reduced insulin secretion," said Dr.
Donath. "If, as we hypothesize, the inhibition of IL-1 beta improves the
condition of insulin-producing cells in patients by breaking the vicious cycle
of glucotoxicity, the implications would be very promising for the treatment of
the disease."
"We continue to develop evidence supporting one of the most significant
potential medical advances in decades -- a move from insulin therapy to
anti-inflammatory treatment of patients with Type 2 diabetes. Our results have
provided not only the safety data that is typical in a Phase 1 trial but also
encouraging signs of biological activity," said Steven B. Engle, XOMA's Chairman
and Chief Executive Officer. "Recently, our first U.S. patent covering XOMA 052
issued and we completed enrollment of the Phase 1 program with 98 patients. We
look forward to initiating Phase 2 trials in the third quarter of 2009."
Detailed Results
The oral presentation at the ADA meeting, "XOMA 052, a potential disease
modifying anti-IL-1 beta antibody, shows sustained HbA1c reduction three (3)
months after a single injection with no increases in safety parameters in
subjects with Type 2 diabetes," describes safety, pharmacokinetics and
biological activity results from two single-dose, placebo-controlled,
dose-escalation Phase 1 studies.
Results from three dose levels were reported for biological activity, and
included 0.01, 0.03 and 0.1 mg/kg, or placebo. Patients were followed for 56
days in the U.S. and for up to 91 days in Switzerland. The overall baseline
characteristics of the XOMA 052 and placebo groups were similar. Data from both
studies were pooled for analyses of HbA1c and hsCRP where possible.
Inflammatory results: Previously reported data for the 28 day time point
demonstrated a rapid and sustained reduction in hsCRP levels. At the day 56/63
time point, hsCRP was reduced a median of 20%, 25% and 49% in the lowest to
highest dose groups, and increased by approximately 33% in the placebo group. At
day 91 in the Swiss patients, hsCRP levels were between 20% and 30% lower than
baseline in all three treatment groups, as compared to returning to baseline for
the placebo group.
Glycemic control results: Previously reported data for the 28 day time point
demonstrated reduced median HbA1c levels for all XOMA 052 dose groups of as much
as 0.6%. Two months after receiving a single dose of XOMA 052, there remained
continued reductions of 0.5% in both the 0.03 and 0.1 mg/kg groups compared to a
decrease of 0.2% in the placebo group, while there was a median increase in
HbA1c of 0.15% in the lowest XOMA 052 dose group. At day 91 in the Swiss
patients, continued HbA1c reductions of 0.5% and 0.65% in the 0.03 and 0.1 mg/kg
groups, respectively, were reported, compared to an increase of 0.1% in the
placebo group, and an increase of 0.3% in the lowest XOMA 052 dose group. One
patient in the treatment group was removed from this analysis due to a baseline
cancer diagnosis. Including this patient in the analysis, the median HbA1c
reduction in the 0.1 mg/kg cohort was 1.1%.
Insulin production, secretion and utilization results: Initial clinical data
evaluating the pancreatic production of insulin utilizing the standard oGTT and
a test of maximal insulin secretion both yielded information that shows that
after a single intravenous dose of XOMA 052 there was improved beta-cell
function lasting out to day 91. This was also evaluated by utilizing the
insulinogenic index which, at Day 28, showed improvement of at least 20% in the
relative amount of insulin secreted compared to the glucose level.
Cytokine results: Positive new data from whole blood assays were presented.
Whole blood assays demonstrated reductions in levels of pro-inflammatory
cytokines including TNF-alpha, IL-6, IL-1 alpha. Further, there was no evidence
of suppressive effects on protective cytokines including interferon-alpha and
IL-1 receptor antagonist, which play an important role in host defense.
"These results demonstrate the potential for XOMA 052 to offer an entirely new
approach for Type 2 diabetes patients by targeting inflammation, rather than
current treatments that force more insulin out of "tired" pancreatic beta cells
or make peripheral cells more sensitive to insulin," said Patrick J. Scannon,
M.D., Ph.D., XOMA's Executive Vice President and Chief Medical Officer.
"Further, some studies have shown that certain diabetes medications may increase
the risk of cardiovascular events in a population already at risk due to obesity
or other factors. The positive effect of XOMA 052 on reducing levels of the
hsCRP cardiovascular risk marker in these trials suggests its potential for a
beneficial systemic anti-inflammatory outcome, and warrants further
investigation in additional trials."
Overview of XOMA 052 Phase 1 Trials
A total of 98 patients were enrolled in the U.S. and Swiss Phase 1 trials, and
included 81 patients who received XOMA 052 and 17 placebo-treated patients. The
U.S. trials included:
* An IV single-dose, dose-escalation part which enrolled 36
patients and evaluated XOMA 052 at 0.01., 0.03, 0.1, 1.0 and
3.0 mg/kg or placebo.
* A subcutaneous single-dose, dose-escalation part which enrolled
20 patients and evaluated 0.03, 0.1 and 0.3 mg/kg doses of
XOMA 052 or placebo.
* A subcutaneous multi-dose, dose-escalation part which enrolled
12 patients and evaluated 0.03 and 0.3 mg/kg doses of XOMA 052
or placebo administered at two week intervals for three doses.
The Swiss trial was an IV single dose, dose-escalation trial which evaluated
XOMA 052 at the same doses of the U.S. single dose except the 3.0 mg/kg dose and
enrolled 30 patients.
Enrollment has been completed in both the U.S. and Swiss Phase 1 trials; patient
follow-up continues for several cohorts. XOMA plans to announce top line results
from all three parts of the U.S. trial in July, and from the Swiss trial by
September. The company also plans to initiate a Phase 2 trial of XOMA 052 in the
third quarter of 2009.
About XOMA 052
XOMA 052 is a potent, humanized monoclonal antibody with the potential to
improve the treatment of patients with a wide variety of inflammatory diseases.
XOMA 052 binds strongly to interleukin-1 beta (IL-1 beta), a pro-inflammatory
cytokine involved in the development of Type 2 diabetes, cardiovascular disease,
rheumatoid arthritis, gout and other diseases. By binding to IL-1 beta, the drug
inhibits the activation of the IL-1 receptor, thereby preventing the cellular
signaling events that produce inflammation. XOMA 052 has a half-life of 22 days.
Based on its binding properties, specificity to IL-1 beta and half-life, XOMA
052 may provide convenient dosing of once per month or less frequently.
XOMA developed XOMA 052 using the company's proprietary antibody technologies,
capabilities and expertise. XOMA owns worldwide rights to the antibody and
related intellectual property. The company is actively pursuing a partnership
for the development and commercialization of XOMA 052. XOMA was recently issued
a U.S. patent for XOMA 052 and similar antibodies which provides patent coverage
into 2027.
About the Interleukin-1 Pathway
The central role of the IL-1 pathway in multiple diseases has been clinically
validated by two FDA-approved therapies and several inhibitors of the
inflammatory IL-1 pathway in clinical development. These disease indications
include rheumatoid arthritis, systemic juvenile idiopathic arthritis, gout,
Muckle-Wells syndrome, and others.
About XOMA
XOMA discovers, develops and manufactures therapeutic antibody therapeutics
designed to treat inflammatory, autoimmune, infectious and cancerous diseases.
The company's proprietary product pipeline includes XOMA 052, an anti-IL-1 beta
antibody, and XOMA 3AB, a biodefense anti-botulism antibody candidate.
XOMA's proprietary development pipeline is primarily funded by multiple revenue
streams resulting from the licensing of its antibody technologies, product
royalties, development collaborations and biodefense contracts. XOMA's
technologies and experienced team have contributed to the success of marketed
antibody products, including LUCENTIS(r) (ranibizumab injection) for wet
age-related macular degeneration and CIMZIA(r) (certolizumab pegol) for
rheumatoid arthritis and Crohn's disease.
The company has a premier antibody discovery and development platform that
incorporates leading antibody phage display libraries and XOMA's proprietary
Human Engineering(tm) and Bacterial Cell Expression and manufacturing
technologies. Bacterial Cell Expression is a key breakthrough biotechnology for
the discovery and manufacturing of antibodies and other proteins. As a result,
more than 50 pharmaceutical and biotechnology companies have signed BCE
licenses.
In addition to developing its own products, XOMA develops products with premier
pharmaceutical companies including Novartis AG, Schering-Plough Research
Institute and Takeda Pharmaceutical Company Limited. XOMA has a fully integrated
product development infrastructure, extending from pre-clinical science to
approval, and a team of about 200 employees at its Berkeley location. For more
information, please visit http://www.xoma.com.
The XOMA Ltd. logo is available at
http://www.globenewswire.com/newsroom/prs/?pkgid=5960
Forward-Looking Statements
Certain statements contained herein concerning the effects and possible dosing
for XOMA 052 plans to initiate a XOMA 052 Phase 2 clinical program, timing of
availability of results of clinical trials and/or other aspects of product
development or that otherwise relate to future periods are 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. These statements are based
on assumptions that may not prove accurate. Actual results could differ
materially from those anticipated due to certain risks inherent in the
biotechnology industry and for companies engaged in the development of new
products in a regulated market.
Among other things, the effects of XOMA 052 may differ in later preclinical or
clinical testing, dosing of XOMA 052 may be affected by later testing results,
the initiation of a Phase 2 clinical trial and/or the timing of availability of
results of clinical trials may be delayed or may never occur as a result of
unavailability of resources, actions or inaction by our present or future
collaboration partners, or unanticipated safety issues.
These and other risks, including those related to XOMA's ability to remain in
compliance with or renegotiate the requirements of its loan agreements; the
declining and generally unstable nature of current economic conditions; the
results of discovery and pre-clinical testing; the timing or results of pending
and future clinical trials (including the design and progress of clinical
trials; safety and efficacy of the products being tested; action, inaction or
delay by the FDA, European or other regulators or their advisory bodies; and
analysis or interpretation by, or submission to, these entities or others of
scientific data); changes in the status of existing collaborative relationships;
the ability of collaborators and other partners to meet their obligations;
XOMA's ability to meet the demands of the United States government agency with
which it has entered into its government contracts; competition; market demands
for products; scale-up and marketing capabilities; availability of additional
licensing or collaboration opportunities; international operations; share price
volatility; XOMA's financing needs and opportunities; uncertainties regarding
the status of biotechnology patents; uncertainties as to the costs of protecting
intellectual property; and risks associated with XOMA's status as a Bermuda
company, are described in more detail in XOMA's most recent filing on Form 10-K
and in other SEC filings. Consider such risks carefully when considering XOMA's
prospects.
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CONTACT: XOMA Ltd.
Company and Investor Contact:
Carol DeGuzman
510-204-7270
deguzman@xoma.com
Porter Novelli Life Sciences
Media Contact:
Carolyn Hawley
619-849-5375
chawley@pnlifesciences.com
