Merck & Co., Inc., Whitehouse Station, N.J., U.S.A., which
operates as Merck, Sharp & Dohme (MSD) in countries outside the U.S.,
announced today that the U.S. Food and Drug Administration (FDA)
approved JANUVIA(TM) (sitagliptin phosphate), the first and only DPP-4
inhibitor available in the United States for the treatment of type 2
diabetes. JANUVIA has been approved as monotherapy and as add-on
therapy to either of two other types of oral diabetes medications,
metformin or thiazolidinediones (TZDs), to improve blood sugar
(glucose) control in patients with type 2 diabetes when diet and
exercise is not enough. The recommended dose of JANUVIA is 100 mg once
daily. JANUVIA should not be used in patients with type 1 diabetes or
for the treatment of diabetic ketoacidosis, as it would not be
effective in these settings.
JANUVIA enhances a natural body system to significantly lower
elevated blood sugar
JANUVIA belongs to a new breakthrough class of prescription
medications called dipeptidyl peptidase-4 (DPP-4) inhibitors that
improves blood sugar control in patients with type 2 diabetes. JANUVIA
enhances a natural body system called the incretin system, which helps
to regulate glucose by affecting the beta cells and alpha cells in the
pancreas. Through DPP-4 inhibition, JANUVIA works only when blood
sugar is elevated to address diminished insulin due to beta-cell
dysfunction and uncontrolled production of glucose by the liver due to
alpha-cell and beta-cell dysfunction.
"Those patients who are unable to adequately manage their type 2
diabetes with lifestyle changes, like healthy eating and increased
physical exercise, and who require medications now have a new product
to help regulate their blood sugar levels," said Edward S. Horton,
M.D., director of clinical research, Joslin Diabetes Center and
professor of medicine, Harvard Medical School, Boston.
"JANUVIA underscores MSD's commitment to the field of diabetes,
and the benefits we strive to bring to patients and physicians who
struggle in the treatment of type 2 diabetes," said Richard T. Clark,
president and chief executive officer, Merck & Co., Inc. "The approval
of JANUVIA is a clear example of MSD's focus on developing innovative
therapies to improve human health around the world."
JANUVIA had an overall incidence of side effects comparable to
placebo
In clinical trials, JANUVIA demonstrated an overall incidence of
side effects comparable to placebo. The most common side effects
reported with JANUVIA (greater than or equal to 5 percent and higher
than placebo) were stuffy or runny nose and sore throat, upper
respiratory infection, and headache.
JANUVIA provides powerful HBA1C(1) reductions as monotherapy
In two double-blind, placebo-controlled studies of 24 weeks
(n=473) and 18 weeks (n=296) in patients with mild to moderate
baseline HBA1C levels (mean 8.0%; enrollment range 7.0% to 10.0%),
JANUVIA 100 mg once-daily showed significant mean differences in HBA1C
from placebo of -0.8% and -0.6%, respectively (p less than 0.001). As
is typical in trials of agents to treat type 2 diabetes, mean response
to JANUVIA in HBA1C lowering appears to be related to the degree of
HBA1C elevation at baseline. In a pooled analysis of these two
monotherapy studies, a pre-specified subgroup analysis showed that
when patients were grouped by baseline HBA1C into those with mildly
elevated HBA1C levels (less than 8%, n=411), moderately elevated HBA1C
levels (greater than or equal to 8% to less than 9%, n=239) and the
highest elevated HBA1C levels (greater than or equal to 9%, n=119),
mean differences in HBA1C from placebo after 18 weeks were -0.6%,
-0.7% and -1.4%, respectively (p less than 0.001 for treatment by
subgroup interactions).
JANUVIA has a significant and complementary effect when added to
metformin or TZDs
JANUVIA addresses two of the three key defects that cause poor
glucose control: diminished insulin release due to beta-cell
dysfunction and uncontrolled production of glucose by the liver due to
alpha-cell and beta-cell dysfunction. By adding JANUVIA to the insulin
sensitizers metformin or pioglitazone (a TZD), the three key defects
of type 2 diabetes can be addressed: insulin resistance, beta-cell
dysfunction (decreased insulin release), and alpha-cell dysfunction
(unsuppressed hepatic glucose production).
In separate 24-week studies of patients with type 2 diabetes who
were inadequately controlled on either metformin or pioglitazone
alone, JANUVIA 100 mg once daily provided a complementary effect.
JANUVIA showed significant mean differences in HBA1C from placebo of
-0.7% in the metformin add-on study (p less than 0.001) and -0.7% in
the pioglitazone add-on study (p less than 0.001). In those same
studies, the mean HBA1C reduction from baseline with JANUVIA was 0.7%
from a mean baseline HBA1C of 8.0% and 0.9% from a mean baseline of
8.1%, respectively.
Approximately twice as many patients got to HBA1C goal of less
than 7% with JANUVIA
In the metformin add-on study, more than twice as many patients
uncontrolled on metformin got to HBA1C goal of less than 7% when
JANUVIA was added (47 percent with JANUVIA and metformin vs. 18
percent for patients continuing on metformin alone) (p less than
0.001). Similarly, in the pioglitazone add-on study, 45 percent of
patients adding JANUVIA to their regimen reached the HBA1C goal of
less than 7% compared with 23 percent who continued on pioglitazone
alone (p less than 0.001).
JANUVIA provides powerful HBA1C lowering through combined
reductions of both PPG and FPG throughout the day
JANUVIA has been demonstrated to provide a 24-hour glucose
response at mealtime, between meals and overnight. In a 24-week,
placebo-controlled study of patients uncontrolled on metformin, adding
JANUVIA 100 mg once daily substantially reduced PPG (or post-meal
glucose) levels by 51 mg/dL and FPG by 25 mg/dL compared to patients
continuing on metformin alone (p less than 0.001).
Treatment with JANUVIA was not associated with weight gain or
increased risk of hypoglycemia
JANUVIA once-daily was weight neutral compared to placebo in
clinical trials. Mean body weight decreased 0.2 kg (vs. 1.1 kg
decrease for placebo) and 0.7 kg (vs. 0.6 kg), respectively, in two
24-week trials: one in patients taking JANUVIA as monotherapy (n=193)
and one in combination with metformin (n=399). The overall incidence
of hypoglycemia in patients treated with JANUVIA 100 mg was similar to
placebo (1.2 percent vs. 0.9 percent, respectively) across the
clinical program. The incidence of selected gastrointestinal adverse
reactions in patients treated with JANUVIA was as follows: abdominal
pain (JANUVIA, 2.3 percent; placebo, 2.1 percent), nausea (1.4
percent, 0.6 percent), and diarrhea (3.0 percent, 2.3 percent).
Glucose-dependent mechanism of action
The novel mechanism of JANUVIA is glucose-dependent, responding to
the presence of elevated glucose and resulting in the release of
insulin and decrease of glucagon only when needed, thereby lowering
the potential for hypoglycemia. By inhibiting the DPP-4 enzyme,
JANUVIA significantly increases the levels of active incretin
hormones, increasing the synthesis and release of insulin from the
pancreatic beta cells and decreasing the release of glucagon from the
pancreatic alpha cells.
Indications and contraindications for JANUVIA
JANUVIA is indicated, as an adjunct to diet and exercise, to
improve glycemic control in patients with type 2 diabetes mellitus.
JANUVIA is also indicated to improve glycemic control, in combination
with metformin or a TZD, in patients with type 2 diabetes when the
single agent alone plus diet and exercise do not provide adequate
glycemic control. JANUVIA should not be used in patients with type 1
diabetes or for the treatment of diabetic ketoacidosis, as it would
not be effective in these settings. There are no contraindications for
JANUVIA.
Selected cautionary information for JANUVIA
Because JANUVIA is renally eliminated, and to achieve plasma
concentrations of JANUVIA similar to those in patients with normal
renal function, a dosage adjustment is recommended in patients with
moderate renal insufficiency and in patients with severe renal
insufficiency or with end-stage renal disease (ESRD) requiring
hemodialysis or peritoneal dialysis. Safety and effectiveness of
JANUVIA in pediatric patients have not been established. There are no
adequate and well-controlled studies in pregnant women. JANUVIA should
be used during pregnancy only if clearly needed. Caution should be
exercised when JANUVIA is administered to a nursing woman.
Dosing of JANUVIA
The recommended dose of JANUVIA is 100 mg once daily, with or
without food, for all approved indications. No dosage adjustment is
needed for patients with mild to moderate hepatic insufficiency or in
patients with mild renal insufficiency (CrCl greater than or equal to
50 mL/min). To achieve plasma concentrations of JANUVIA similar to
those in patients with normal renal function, lower dosages are
recommended in patients with moderate and severe renal insufficiency
as well as in ESRD patients requiring hemodialysis. For patients with
moderate renal insufficiency (CrCl greater than or equal to 30 to less
than 50 mL/min), the dose of JANUVIA is 50 mg once daily. For those
with severe renal insufficiency (CrCl less than 30 mL/min) or with
ESRD requiring dialysis, the dose of JANUVIA is 25 mg once daily.
Because there is a need for dosage adjustment based upon renal
function, assessment of renal function is recommended prior to
initiation of JANUVIA and periodically thereafter.
Pricing and availability of JANUVIA
The price of once-daily JANUVIA in the United States will be $4.86
per tablet. JANUVIA will be broadly available in pharmacies in the
United States in the near future.
About type 2 diabetes
Type 2 diabetes is a condition in which the body has elevated
blood sugar or glucose. With type 2 diabetes, the body may not make
enough insulin, the insulin that the body produces may not work as
well as it should, and/or the liver may release too much glucose.
Nearly 21 million people in the United States (7 percent of the
population) have diabetes, with type 2 accounting for 90-95 percent of
cases. Approximately half of people diagnosed with type 2 diabetes
have not achieved adequate control of their blood sugar levels.
Patients with diabetes can develop heart disease, kidney disease,
blindness, vascular or neurological problems that can lead to
amputation and can suffer increased rates of mortality.
It is estimated that one in three Americans born in 2000 will
develop diabetes sometime during their lifetime. There are currently
more than 230 million people with diabetes worldwide, and if nothing
is done to slow the epidemic, the worldwide number may exceed 350
million by 2025. The American Diabetes Association recommends that
patients with type 2 diabetes achieve a target HBA1C level of less
than 7%, while the American Academy of Clinical Endocrinologists
recommends a target HBA1C level of less than 6.5%.
Expanding clinical development program for JANUVIA
MSD's clinical development program for JANUVIA is robust and
continues to expand with 43 studies completed or under way, and four
more studies set to begin this year. There are about 6,700 patients in
the Company's clinical studies with about 4,700 of these patients
being treated with JANUVIA. Additionally, about 1,100 patients have
been treated with JANUVIA for more than a year.
JANUVIA also is being investigated as part of a single tablet
combination with metformin (MK-0431A). MK-0431A has been accepted for
standard review by the FDA, and an FDA action is expected by the end
of March 2007. Regulatory filings in countries outside the United
States are moving forward as planned.
About Merck & Co., Inc.
Merck & Co., Inc. which operates as Merck, Sharp & Dohme (MSD) in
countries outside the U.S., is a global research-driven pharmaceutical
company dedicated to putting patients first. Established in 1891,
Merck currently discovers, develops, manufactures and markets vaccines
and medicines to address unmet medical needs. The Company devotes
extensive efforts to increase access to medicines through far-reaching
programs that not only donate Merck medicines but help deliver them to
the people who need them. Merck also publishes unbiased health
information as a not-for-profit service. For more information, visit
www.merck.com.
Forward-looking statement
This press release contains "forward-looking statements" as that
term is defined in the Private Securities Litigation Reform Act of
1995. These statements are based on management's current expectations
and involve risks and uncertainties, which may cause results to differ
materially from those set forth in the statements. The forward-looking
statements may include statements regarding product development,
product potential or financial performance. No forward-looking
statement can be guaranteed, and actual results may differ materially
from those projected. MSD undertakes no obligation to publicly update
any forward-looking statement, whether as a result of new information,
future events, or otherwise. Forward-looking statements in this press
release should be evaluated together with the many uncertainties that
affect MSD's business, particularly those mentioned in the cautionary
statements in Item 1 of MSD's Form 10-K for the year ended Dec. 31,
2005, and in its periodic reports on Form 10-Q and Form 8-K, which the
Company incorporates by reference.
NOTE: The views stated herein are those of Dr. Edward Horton and
do not necessarily represent the views of Joslin Diabetes Center.
Joslin Diabetes Center does not endorse products, did not participate
in any tests for the product JANUVIA and makes no representations as
to its quality or efficacy.
JANUVIA(TM) is a registered trademark of Merck & Co., Inc.,
Whitehouse Station, N.J., U.S.A., known as Merck, Sharp & Dohme
outside the U.S.A.
(1) HBA1C is a measure of a person's average blood glucose over a
two- to three-month period.
