Canagliflozin Provided Substantial and Sustained Glycemic Improvements as Monotherapy and in Add-On Combinations in Adults with Type 2 Diabetes in Five Phase 3 Studies

Philadelphia (ots/PRNewswire) -

Canagliflozin Provides Greater Reduction of A1C Levels in
Adults with Type 2

Diabetes in 52-Week Head-to-Head Studies Compared to Sitagliptin
and Glimepiride

Janssen Research & Development, LLC (Janssen) presented results
from five Phase 3 clinical studies evaluating canagliflozin in
monotherapy and in add-on combination use showing that canagliflozin
provided substantial and sustained glycemic improvements in adult
patients with type 2 diabetes, and was generally well tolerated. In
two of these studies comparing canagliflozin to current standard
treatments, sitagliptin and glimepiride, canagliflozin dosed
once-daily at 300 mg provided significantly greater reductions in A1C
levels relative to both comparators with similar overall incidence of
adverse events. These studies were presented today as late-breaking
poster presentations at the 72nd American Diabetes Association (ADA)
Annual Scientific Sessions.

Canagliflozin is an investigational sodium glucose co-transporter
2 (SGLT2) inhibitor for the treatment of patients with type 2
diabetes. The kidneys of people with type 2 diabetes reabsorb greater
amounts of glucose back into the body compared to non-diabetic
people, which may contribute to elevated glucose levels.
Canagliflozin blocks the reabsorption of glucose by the kidney,
increasing glucose excretion and lowering blood glucose levels.

"Type 2 diabetes is a chronic condition that over time may
require the use of combinations of antihyperglycemic agents,
including insulin, to maintain optimal glycemic control which is a
primary goal of treatment," said William T. Cefalu, M.D., Chief of
the Joint Program on Diabetes, Endocrinology and Metabolism of the
Pennington Biomedical Research Center & Louisiana State University
Health Sciences Center School of Medicine, and lead investigator on
the DIA3009 study. "The sustained glucose control and low rate of
occurrence of hypoglycemia shown with canagliflozin, an SGLT2
inhibitor, as compared to glimepiride when evaluated over a 52-week
period in this comparative study is very promising. When combined
with the other clinical benefits, the data suggests that this class
of agents may provide an additional and valuable treatment option for
people with type 2 diabetes."

The global Phase 3 canagliflozin clinical program enrolled more
than 10,300 patients in nine studies, and is the largest late-stage
development program for an investigational pharmacologic product for
the treatment of type 2 diabetes submitted to health authorities to
date. The Phase 3 clinical program evaluated the safety and efficacy
of canagliflozin across the spectrum of type 2 diabetes management,
from adult patients treated only with diet and exercise to those
requiring insulin injections to maintain glycemic control. The
program also included three large studies in special populations:
older patients with type 2 diabetes, patients with type 2 diabetes
who had moderate renal impairment, and patients with type 2 diabetes
who have or were considered to be at high risk for cardiovascular
disease. On May 31, 2012, Janssen submitted a New Drug Application to
the U.S. Food and Drug Administration seeking approval for the use of
canagliflozin as a treatment for adult patients with type 2 diabetes.

"The results in each of these studies suggest that canagliflozin
could provide an effective therapeutic option for adults with type 2
diabetes in a range of clinical settings," said Kirk Ways, M.D.,
Ph.D., Vice President and Compound Development Team Leader for
canagliflozin at Janssen. "Canagliflozin has the potential to be
administered as monotherapy in patients who are inadequately
controlled with diet and exercise alone, as an add-on therapy in
patients being treated with metformin alone or in combination with
sulfonylureas, and in patients with moderate renal impairment. As
part of our commitment to develop new therapeutic options for unmet
patient needs in the treatment of type 2 diabetes, we look forward to
presenting data from the remaining Phase 3 canagliflozin clinical
trials in the near future."

About the Studies

DIA3015 is a 52-week randomized, double-blind, active-controlled
Phase 3 study in 755 adult patients with inadequate glycemic control
on maximally effective doses of metformin and sulfonylurea. Patients
were given once-daily doses of canagliflozin (300 mg) or sitagliptin
(100 mg). Patients treated with canagliflozin had a substantial and
sustained decrease in A1C levels, with a significantly greater
reduction relative to sitagliptin after 52 weeks (-0.37, 95% CI
-0.50; -0.25). Based on protocol-specified withdrawal criteria, more
subjects discontinued from the study due to loss of glycemic control
in the sitagliptin treatment arm (22.5%) than the canagliflozin arm
(10.6%). In the key secondary endpoint measures, patients treated
with canagliflozin 300 mg also had greater weight loss compared to
sitagliptin (percent changes of -2.5 and 0.3, respectively);
reductions in fasting plasma glucose changes were consistent with the
primary A1C endpoint (-29.9 and -5.9 mg/dL, respectively); systolic
blood pressure was reduced with canagliflozin (-5.1 and 0.9 mmHg,
respectively). Canagliflozin raised HDL-C relative to sitagliptin (%
change, 7.6 and 0.6, respectively), and also LDL-C (% change 11.7 and
5.2, respectively).

The overall incidence of treatment-emergent adverse events (AEs)
was similar in the canagliflozin (76.7%) and sitagliptin (77.5%)
groups. The incidence of serious AEs were low and similar in both
groups (6.4% and 5.6%, and respectively, in the canagliflozin and
sitagliptin groups); discontinuations due to AEs were low in both
groups but higher in the canagliflozin than in the sitagliptin group
(5.3%, and 2.9%, respectively). AEs related to genital mycotic
infections in men and women, and AEs related to an osmotic diuresis
such as increased urination, were more frequent in patients treated
with canagliflozin than sitagliptin; a similar incidence of urinary
tract infections was seen in the two treatment groups. The genital
infections and osmotic diuresis related AEs were generally mild to
moderate in intensity and infrequently led to discontinuation; most
genital infections responded to topical or oral antifungal therapy. A
similar incidence of hypoglycemic episodes was reported with
canagliflozin and sitagliptin.

To access the abstract, visit
http://www.abstractsonline.com/plan/AdvancedSearch.aspx and search
for abstract number 50-LB.

DIA3009 is a 52-week randomized, double-blind, active-controlled
Phase 3 trial in 1,450 adult patients with inadequate glycemic
control on maximally effective doses of metformin. Patients were
randomized and treated once daily with either canagliflozin (100 mg
or 300 mg) or glimepiride (with up-titration of glimepiride allowed
throughout the 52-week period). Patients treated with canagliflozin
had a sustained decrease in A1C, with statistically greater
A1C-lowering for canagliflozin 300 mg after 52 weeks when compared to
glimepiride (-0.93% and -0.81%, respectively, with the between group
difference of -0.12%, 95% CI -0.22; -0.02); the decrease in A1C with
canagliflozin 100 mg (-0.82%) was similar to that for glimepiride
(between group difference of -0.01%, 95% CI -0.11; 0.09). In the key
secondary endpoint measures, both the 300 mg and 100 mg canagliflozin
dose groups provided reductions in body weight, with no notable
change in the glimepiride group (body weight % change, -4.7 and -4.2
and 1.0, respectively). Hypoglycemia episodes occurred at a low
incidence with canagliflozin 300 mg and 100 mg, and at a higher
incidence with glimepiride (% of patients with 1 or more episodes:
4.9 and 5.6 and 34.2, respectively). Reductions in fasting plasma
glucose were consistent with the primary endpoint for canagliflozin
300 mg and 100 mg and glimepiride (-27.5 and -24.3 and -18.3 mg/dL,
respectively); other secondary endpoints included reductions in
systolic blood pressure with both doses of canagliflozin and no
notable change with glimepiride (-4.6 and -3.3 and 0.2 mmHg,
respectively); HDL-C increased with both 300 mg and 100 mg doses of
canagliflozin, with no notable change with glimepiride (% change, 9.0
and 7.9 and 0.3, respectively); LDL-C rose with both doses of
canagliflozin more than with glimepiride (% change, 14.1 and 9.6 and
5.0, respectively).

The incidence of AEs and discontinuations due to AEs were
generally similar across all treatment arms. AEs were mild to
moderate and the overall incidence was balanced across treatment
arms. Adverse events related to osmotic diuresis such as increased
urination, genital mycotic infections in men and women, and urinary
tract infections were more frequent in patients treated with
canagliflozin than glimepiride; these specific adverse events were
generally mild or moderate in intensity and infrequently led to
discontinuation.

To access the abstract, visit
http://www.abstractsonline.com/plan/AdvancedSearch.aspx and search
for abstract number 38-LB.

Janssen presented results from three additional Phase 3 studies
at this year's ADA meeting, which also demonstrate the potential
value of canagliflozin across the spectrum of type 2 diabetes
management including use in monotherapy, in add-on combination, and
in patients with moderate renal impairment.

- "Canagliflozin, a Sodium Glucose Co-Transporter 2 Inhibitor, Improves
Glycemia and is Well Tolerated in Type 2 Diabetes Mellitus Subjects with Moderate
Renal Impairment" on June 10 (
http://www.abstractsonline.com/plan/AdvancedSearch.aspx, abstract 41-LB).
- "Canagliflozin, a Sodium Glucose Co-Transporter 2 Inhibitor, Improves Glycemic
Control and Lowers Body Weight in Subjects With Type 2 Diabetes Inadequately
Controlled With Diet and Exercise" on June 9 (
http://www.abstractsonline.com/plan/AdvancedSearch.aspx, abstract 81-OR).
- "Canagliflozin, a Sodium Glucose Co-Transporter 2 Inhibitor, Improves Glycemic
Control and Reduces Body Weight in Subjects with Type 2 Diabetes Inadequately
Controlled With Metformin and Sulfonylurea" on June 9 (
http://www.abstractsonline.com/plan/AdvancedSearch.aspx, abstract 1022-P).

Janssen and its affiliates have rights to canagliflozin through a
license agreement with Mitsubishi Tanabe Pharma Corporation. Janssen
Pharmaceuticals, Inc. and its affiliates have marketing rights in
North America, South America, Europe, Middle East, Africa, Australia,
New Zealand and parts of Asia.

About Janssen Research & Development, LLC

Janssen Research & Development, LLC is headquartered in Raritan,
N.J. and has affiliated facilities in Europe, the United States and
Asia. Janssen Research & Development is leveraging a combination of
internal and external innovation to discover and develop novel
medicines and solutions in five distinct therapeutic areas:
Neuroscience, Oncology, Immunology, Infectious Diseases and Vaccines,
and Cardiovascular and Metabolism. Janssen Research & Development is
part of the Janssen Pharmaceutical Companies of Johnson & Johnson.

For more information about Janssen Research & Development, LLC
visit http://www.janssenrnd.com.

About Janssen

The Janssen Pharmaceutical Companies of Johnson & Johnson are
dedicated to addressing and solving the most important unmet medical
needs of our time, including oncology, immunology, neuroscience,
infectious disease, and cardiovascular and metabolic diseases. Driven
by our commitment to patients, we develop innovative products,
services and healthcare solutions to help people throughout the
world.

More information can be found at http://www.janssen-emea.com

(This press release contains "forward-looking statements" as
defined in the Private Securities Litigation Reform Act of 1995. The
reader is cautioned not to rely on these forward-looking statements.
These statements are based on current expectations of future events.
If underlying assumptions prove inaccurate or unknown risks or
uncertainties materialize, actual results could vary materially from
the expectations and projections of Janssen Research & Development,
LLC and/or Johnson & Johnson. Risks and uncertainties include, but
are not limited to, general industry conditions and competition;
economic factors, such as interest rate and currency exchange rate
fluctuations; technological advances, new products and patents
attained by competitors; challenges inherent in new product
development, including obtaining regulatory approvals; challenges to
patents; changes in behavior and spending patterns or financial
distress of purchasers of healthcare products and services; changes
to governmental laws and regulations and domestic and foreign health
care reforms; trends toward health care cost containment; and
increased scrutiny of the healthcare industry by government agencies.
A further list and description of these risks, uncertainties and
other factors can be found in Exhibit 99 of Johnson & Johnson's
Annual Report on Form 10-K for the fiscal year ended January 1, 2012.
Copies of this Form 10-K, as well as subsequent filings, are
available online at http://www.sec.gov, http://www.jnj.com or on
request from Johnson & Johnson. Neither Janssen Research &
Development, LLC nor Johnson & Johnson undertake to update any
forward-looking statements as a result of new information or future
events or developments.)

ots Originaltext: Janssen Pharmaceutica
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