TITUSVILLE, N.J. and
ORLANDO, Fla., June 24, 2018
/PRNewswire/ -- The Janssen Pharmaceutical Companies of
Johnson & Johnson today announced late-breaking results of a
new real-world analysis of more than 700,000 U.S. T2D patients,
which found no increased risk of below-knee lower extremity (BKLE)
amputation with INVOKANA® (canagliflozin) compared to
other sodium glucose cotransporter 2 inhibitors (SGLT2i) or
non-SGLT2i anti-hyperglycemic medicines. In addition to the general
T2D population, similar results were also seen in a sub-set of
patients with T2D and established cardiovascular disease.
OBSERVE-4D is the largest, most comprehensive real-world
observational study to evaluate the risk of BKLE amputation and
hospitalization for heart failure (HHF) across anti-hyperglycemic
therapies. Full findings from the late-breaking presentation were
highlighted today in the American Diabetes Association's (ADA)
78th Official Press Program in Orlando, Florida and simultaneously published
in Diabetes, Obesity and Metabolism.
"We initiated OBSERVE-4D to better characterize the real-world
use of INVOKANA® and the SGLT2i class, so physicians and
their patients could make better informed treatment decisions,"
said Paul Burton, MD, PhD, FACC,
Vice President, Medical Affairs, Janssen Scientific Affairs, LLC.
"Prior to this analysis, no real-world study had evaluated
head-to-head comparative evidence on amputation and hospitalization
for heart failure across individual SGLT2i medicines."
Researchers observed no increased risks across the therapy
comparisons for BKLE amputations in the general T2D population:
- INVOKANA® vs. all non-SGLT2i medicines: HR (95% CI):
0.75 (0.40, 1.41), p=0.30.
- INVOKANA® vs. other SGLT2i medicines: HR (95% CI):
1.14 (0.67, 1.93), p=0.53.
- Other SGLT2i medicines vs. all non-SGLT2i medicines: HR (95%
CI): 0.84 (0.27, 2.55), p=0.68.
These amputation rates were also consistent in a sub-population
with established cardiovascular disease:
- INVOKANA® vs. all non-SGLT2i medicines: HR (95% CI):
0.72 (0.34-1.51), p=0.29.
- INVOKANA® vs. other SGLT2i medicines: HR (95% CI):
1.08 (0.63-1.82), p=0.85.
"OBSERVE-4D depicts how INVOKANA® and other SGLT2is
are being used by people with type 2 diabetes, including in those
with established CV disease, in the real world," said John Buse, MD, PhD, Chief of the Division of
Endocrinology and Director of the Diabetes Center, University of North Carolina School of Medicine,
Chapel Hill, North Carolina. "The
overall benefit-risk profile of SGLT2is is positive, and physicians
should feel comfortable and confident in prescribing the class to
their appropriate patients."
In addition to showing no significant imbalance of BKLE
amputation, the study also identified a HHF reduction in the
general T2D population that was consistent with rates seen in
randomized clinical trials and other real-world evidence studies
including the SGLT2i class. The HHF result is a positive
confirmatory finding and supports the internal validity of the
study results:
- INVOKANA® was associated with a 61 percent reduction
in the risk of HHF compared to non-SGLT2i medicines: HR=0.39 (95%
CI): 0.26, 0.60, p=0.01.
- Similar risk reductions were seen with INVOKANA® vs.
other SGLT2i medicines: HR (CI) 0.90: 0.71, 1.13, p=0.28.
"The OBSERVE-4D findings are welcome news for patients and the
physicians who treat them," said Ralph
DeFronzo, MD, professor of medicine and chief of the
Division of Diabetes at UT Health. "These data reaffirm the
confidence we've always had in the SGLT2i class."
SGLT2is, including INVOKANA®, are anti-hyperglycemic
therapies prescribed for the treatment of T2D. Evidence was
published last year from the CANVAS (CANagliflozin cardioVascular
Assessment Study) Program, which was the first program to assess
the efficacy, safety, and durability of INVOKANA® in
more than 10,000 patients with T2D who had either a prior history
of CV disease or at least two CV risk factors.
However, an increased risk of BKLE amputation was seen with
INVOKANA® in the CANVAS Program and is reflected in its
U.S. prescribing information.1,2
About OBSERVE-4D
The OBSERVE-4D analysis was based on data from four large U.S.
medical claims databases, and included 714,582 adults with T2D
across multiple categories: those who took INVOKANA®
(142,800), other SGLT2i therapies (110,897, empagliflozin or
dapagliflozin), or non-SGLT2i therapies (460,885), defined as any
dipeptidyl peptidase-4 inhibitor (DPP-4i), glucagon-like peptide-1
(GLP-1) receptor agonist, or other anti-hyperglycemic agents
(acarbose, bromocriptine, miglitol, nateglinide, and
repaglinide).
Patients represented a diverse population covered by
employer-sponsored plans, Medicare or Medicaid. The two primary
outcomes were HHF and BKLE amputation. Patients in the different
treatment groups were matched based on demographic and clinical
characteristics, including the presence of other diseases and their
associated mortality risks.
Investigators found similar results for HHF and BKLE amputation
in a separate sub-group analysis of 215,633 patients who had
established CV disease, representing 30 percent of the entire
population from the four databases:
- Truven MarketScan® Commercial Claims and Encounters:
Active employees, early retirees, and their dependents insured by
employer-sponsored plans
- Truven MarketScan® Multi-state Medicaid: Medicaid
enrollees from multiple states
- Truven MarketScan® Medicare Supplemental
Beneficiaries: Medicare-eligible active and retired employees and
their Medicare-eligible dependents from employer-sponsored
supplemental plans
- OptumInsight's ClinformaticsTM Datamart: Individuals
fully insured in commercial plans or in administrative services
only and commercial Medicare
To advance transparency and ensure open access for future
research, the study protocol and all results are publicly available
at: data.ohdsi.org/AhasHfBkleAmputation. Because of the volume and
complexity of the analyses, the researchers created an interactive
matrix that allows other scientists to fully explore the data.
Real-World Study Limitations
Real-world data have the potential to supplement randomized
controlled trial data by providing additional information about how
a medicine performs in routine medical practice. However, they have
limitations and cannot be used as stand-alone evidence to validate
the efficacy or safety of a treatment.
OBSERVE-4D investigators also noted that although these results
are derived from multiple large datasets reflecting current use in
the United States, the number of
patients with long-duration exposure (>6 months) and the study's
power are limited. Further study will help to fully understand the
issue.
WHAT IS INVOKANA®?
INVOKANA®
(canagliflozin) is a prescription medicine used along with diet and
exercise to lower blood sugar in adults with type 2 diabetes.
INVOKANA® is not for people with type 1 diabetes or with
diabetic ketoacidosis (increased ketones in blood or urine). It is
not known if INVOKANA® is safe and effective in children
under 18 years of age. The recommended starting dose is 100 mg
once daily, taken before the first meal of the day. The dose can be
increased to 300 mg once daily in patients tolerating
INVOKANA® 100 mg once daily who have an eGFR of 60
mL/min/1.73 m2 or greater and require additional glycemic
control.
IMPORTANT SAFETY INFORMATION
INVOKANA® (canagliflozin) can cause important side
effects, including:
- Amputations. INVOKANA® may increase your risk of
lower-limb amputations. Amputations mainly involve removal of the
toe or part of the foot; however, amputations involving the leg,
below and above the knee, have also occurred. Some people had more
than one amputation, some on both sides of the body. You may be
at a higher risk of lower-limb amputation if you: have a history of
amputation, have heart disease or are at risk for heart disease,
have had blocked or narrowed blood vessels (usually in leg), have
damage to the nerves (neuropathy) in the leg, or have had diabetic
foot ulcers or sores. Call your doctor right away if you have
new pain or tenderness, any sores, ulcers, or infections in your
leg or foot. Your doctor may decide to stop your
INVOKANA® for a while if you have any of these signs or
symptoms. Talk to your doctor about proper foot care
- Dehydration. INVOKANA® can cause some people to
become dehydrated (the loss of too much body water), which may
cause you to feel dizzy, faint, lightheaded, or weak, especially
when you stand up (orthostatic hypotension). You may be at
higher risk of dehydration if you have low blood pressure, take
medicines to lower your blood pressure (including diuretics [water
pills]), are on a low sodium (salt) diet, have kidney problems, or
are 65 years of age or older
- Vaginal yeast infection. Women who take
INVOKANA® may get vaginal yeast infections. Symptoms
include: vaginal odor, white or yellowish vaginal discharge
(discharge may be lumpy or look like cottage cheese), or vaginal
itching
- Yeast infection of the penis (balanitis or
balanoposthitis). Men who take INVOKANA® may get a
yeast infection of the skin around the penis. Symptoms include:
redness, itching, or swelling of the penis; rash of the penis;
foul-smelling discharge from the penis; or pain in the skin around
penis
Talk to your doctor about what to do if you get symptoms of a
yeast infection of the vagina or penis.
Do not take INVOKANA® if you:
- are allergic to canagliflozin or any of the ingredients in
INVOKANA®. Symptoms of allergic reaction may include:
rash; raised red patches on your skin (hives); or swelling of the
face, lips, tongue, and throat that may cause difficulty in
breathing or swallowing
- have severe kidney problems or are on dialysis
Before you take INVOKANA®, tell your doctor if
you have a history of amputation; heart disease or are at risk
for heart disease; blocked or narrowed blood vessels (usually in
leg); damage to the nerves (neuropathy) of your leg; diabetic foot
ulcers or sores; kidney problems; liver problems; history of
urinary tract infections or problems with urination; are on a low
sodium (salt) diet; are going to have surgery; are eating less due
to illness, surgery, or change in diet; pancreas problems; drink
alcohol very often (or drink a lot of alcohol in short-term); ever
had an allergic reaction to INVOKANA®; or have other
medical conditions.
Tell your doctor if you are or plan to become pregnant, are
breastfeeding, or plan to breastfeed. INVOKANA® may
harm your unborn baby. If you become pregnant while taking
INVOKANA®, tell your doctor right away.
INVOKANA® may pass into your breast milk and may harm
your baby. Do not breastfeed while taking INVOKANA®.
Tell your doctor about all the medicines you take, including
prescription and non-prescription medicines, vitamins, and herbal
supplements. Especially tell your doctor if you take diuretics
(water pills), rifampin (used to treat or prevent tuberculosis),
phenytoin or phenobarbital (used to control seizures), ritonavir
(Norvir®, Kaletra® – used to treat HIV
infection), or digoxin (Lanoxin® – used to treat heart
problems).
Possible Side Effects of
INVOKANA®
INVOKANA® may cause
serious side effects, including:
- Ketoacidosis (increased ketones in your blood or urine).
Ketoacidosis has happened in people who have type 1 or type 2
diabetes, during treatment with INVOKANA®.
Ketoacidosis is a serious condition, which may need to be treated
in a hospital. Ketoacidosis may lead to death. Ketoacidosis can
happen with INVOKANA® even if your blood sugar is less
than 250 mg/dL. Stop taking INVOKANA® and call your
doctor right away if you get any of the following symptoms: nausea,
vomiting, stomach-area pain, tiredness, or trouble
breathing
- Kidney problems. Sudden kidney injury has happened to
people taking INVOKANA®. Talk to your doctor right away
if you: 1) reduce the amount of food or liquid you drink, if you
are sick, or cannot eat or 2) you start to lose liquids from your
body from vomiting, diarrhea, or being in the sun too long
- A high amount of potassium in your blood
(hyperkalemia)
- Serious Urinary Tract Infections may lead to
hospitalization and have happened in people taking
INVOKANA®. Tell your doctor if you have signs or
symptoms of a urinary tract infection such as: burning feeling
while urinating, need to urinate often or right away, pain in the
lower part of your stomach (pelvis), or blood in the urine. Some
people may also have high fever, back pain, nausea, or
vomiting
- Low blood sugar (hypoglycemia). If you take
INVOKANA® with another medicine that can cause low blood
sugar, such as a sulfonylurea or insulin, your risk of getting low
blood sugar is higher. The dose of your sulfonylurea medicine or
insulin may need to be lowered while you take
INVOKANA®
Signs and symptoms of low blood sugar may include: headache,
drowsiness, weakness, dizziness, confusion, irritability, hunger,
fast heartbeat, sweating, shaking, or feeling jittery.
Serious allergic reaction. If you have any symptoms of a
serious allergic reaction, stop taking INVOKANA® and
call your doctor right away or go to the nearest hospital emergency
room.
Broken Bones (fractures). Bone fractures have been seen
in patients taking INVOKANA®. Talk to your doctor about
factors that may increase your risk of bone fracture.
The most common side effects of INVOKANA® include:
vaginal yeast infections and yeast infections of the penis; changes
in urination, including urgent need to urinate more often, in
larger amounts, or at night.
Tell your doctor if you have any side effect that bothers you or
that does not go away. Call your doctor for medical advice about
side effects. You may report side effects to FDA at 1-800-FDA-1088.
You may also report side effects to Janssen Scientific Affairs, LLC
at 1-800-526-7736.
Please see full Product Information, including
Boxed Warning, and Medication Guide for
INVOKANA®.
Janssen Pharmaceuticals, Inc. and its affiliates have rights to
canagliflozin through a license agreement with Mitsubishi Tanabe
Pharma Corporation, including in the
United States. Trademarks are those of their respective
owners.
About the Janssen Pharmaceutical Companies
At the Janssen Pharmaceutical Companies of Johnson & Johnson,
we are working to create a world without disease. Transforming
lives by finding new and better ways to prevent, intercept, treat
and cure disease inspires us. We bring together the best minds and
pursue the most promising science. We are Janssen. We collaborate
with the world for the health of everyone in it. Learn more
at www.janssen.com. Follow us on Twitter at @JanssenUS.
Janssen Pharmaceuticals, Inc. and Janssen Scientific Affairs, LLC
are part of the Janssen Pharmaceutical Companies of Johnson &
Johnson.
Cautions Concerning Forward-Looking Statement
This press release contains "forward-looking statements" as
defined in the Private Securities Litigation Reform Act of 1995
regarding the potential benefits and further development of
INVOKANA® (canagliflozin). 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 known or unknown risks
or uncertainties materialize, actual results could vary materially
from the expectations and projections of Janssen Scientific
Affairs, LLC, any of the other Janssen Pharmaceutical Companies
and/or Johnson & Johnson. Risks and uncertainties include, but
are not limited to: challenges and uncertainties inherent in
product research and development, including the uncertainty of
clinical success and of obtaining regulatory approvals; uncertainty
of commercial success; manufacturing difficulties and delays;
competition, including technological advances, new products and
patents attained by competitors; challenges to patents; product
efficacy or safety concerns resulting in product recalls or
regulatory action; changes in behavior and spending patterns of
purchasers of health care products and services; changes to
applicable laws and regulations, including global health care
reforms; and trends toward health care cost containment. A further
list and descriptions of these risks, uncertainties and other
factors can be found in Johnson & Johnson's Annual Report on
Form 10-K for the fiscal year ended December
31, 2017, including in the sections captioned
"Cautionary Note Regarding Forward-Looking Statements" and "Item
1A. Risk Factors," and in the company's subsequent Quarterly
Reports on Form 10-Q, and other filings with the Securities and
Exchange Commission. Copies of these filings are available online
at www.sec.gov, www.jnj.com or
on request from Johnson & Johnson. None of the Janssen
Pharmaceutical Companies or Johnson & Johnson undertakes to
update any forward-looking statement as a result of new information
or future events or developments.
1 Neal B, Perkovic V, Mahaffey KW, et al.
Canagliflozin and cardiovascular and renal events in type 2
diabetes. N Engl J Med. 2017;377(7):644-657.
2 INVOKANA® (canagliflozin) U.S. Prescribing
Information. Available at
http://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/INVOKANA-pi.pdf.
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