FDA Issues Complete Response Letter for Canagliflozin/Metformin Fixed-Dose Combination Therapy for Type 2 Diabetes

  FDA Issues Complete Response Letter for Canagliflozin/Metformin Fixed-Dose
                   Combination Therapy for Type 2 Diabetes

PR Newswire

RARITAN, N.J., Dec. 12, 2013

RARITAN, N.J., Dec. 12, 2013 /PRNewswire/ --Janssen Research & Development,
LLC (Janssen) today announced it has received from the U.S. Food and Drug
Administration (FDA) a complete response letter regarding its New Drug
Application (NDA) for a fixed-dose combination (FDC) of canagliflozin and
immediate-release metformin to treat adults with type 2 diabetes.

The complete response letter related to the NDA requested additional
information to support the comparability of the twice-daily dosing regimen of
canagliflozin -- as part of the canagliflozin and metformin FDC -- and the
once-daily dosing of canagliflozin as a single agent. Janssen believes it can
supply this information based on available clinical data from the
comprehensive Phase 3 clinical development program for canagliflozin.

"We continue to have productive discussions with the FDA and will work closely
with the agency to advance this application," said Norman Rosenthal, MD, FACE,
FACP, canagliflozin compound development team leader, Janssen Research &
Development, LLC. "We look forward to addressing questions from the FDA as
soon as possible and remain committed to providing therapeutic options that
meet the needs of the type 2 diabetes community."

Canagliflozin is an oral medication that selectively inhibits sodium glucose
co-transporter 2 (SGLT2), a carrier responsible for the reabsorption of
glucose by the kidney, thereby promoting the loss of glucose in the urine and
lowering blood glucose levels in adults with type 2 diabetes. Metformin is a
first-line oral medication that can be used alone or with other medications,
including insulin, to treat type 2 diabetes. Metformin lowers blood glucose
levels by decreasing the amount of glucose made by the liver.

If approved, the canagliflozin and metformin fixed-dose combination could
provide convenience for patients who may benefit from the two diabetes
medications in one tablet. Janssen announced the submission of the
canagliflozin/metformin fixed-dose combination therapy NDA on December 12,

In March of this year, the FDA approved canagliflozin (INVOKANA^®) as a single
agent as an adjunct to diet and exercise to lower blood sugar in adults with
type 2 diabetes. INVOKANA^® has since been widely adopted and today it is the
number one branded therapy prescribed by U.S. endocrinologists when adding or
switching non-insulin type 2 diabetes medications.

INVOKANA^® is the first and only sodium glucose co-transporter 2 (SGLT2)
inhibitor available in the United States.

INVOKANA^® has been studied as monotherapy and in combination with other type
2 diabetes therapies. The comprehensive global Phase 3 clinical development
program for INVOKANA^® enrolled 10,285 patients in nine studies and was one of
the largest clinical programs in type 2 diabetes submitted to health
authorities to date. In clinical studies, patients on INVOKANA^® therapy were
shown to have greater reductions in A1C as well as greater reductions in body
weight and systolic blood pressure versus current standard treatment
sitagliptin. A1C is the percent of red blood cell hemoglobin with glucose
attached to it and an indicator of average blood glucose over the previous two
to three months.

The most common adverse events with INVOKANA^® are genital mycotic (fungal)
infections, urinary tract infections and increased urination. These specific
adverse events were generally mild to moderate in intensity and infrequently
led to discontinuation in Phase 3 studies.

About Type 2 Diabetes
Approximately 25.8 million Americans and an estimated 371 million people
worldwide are living with diabetes. Type 2 diabetes comprises 90 percent of
people with diabetes, which is chronic and affects the body's ability to
metabolize sugar (glucose), and is characterized by the inability of
pancreatic beta cell function to keep up with the body's demand for insulin.

An estimated 44 percent of the global diabetes burden is attributable to being
overweight and obesity. In most people at risk for type 2 diabetes, obesity
causes the body to resist the action of insulin, and if the pancreatic beta
cells cannot produce enough insulin, hyperglycemia and type 2 diabetes ensue.

Nearly half of adults with type 2 diabetes do not achieve recommended levels
of glucose control. If left uncontrolled, type 2 diabetes can lead to serious
complications. Improved glycemic control has been demonstrated to reduce the
onset and progression of these complications.


  oINVOKANA^® is a prescription medicine used along with diet and exercise to
    lower blood sugar in adults with type2 diabetes.
  oINVOKANA^® is not for people with type1 diabetes.
  oINVOKANA^® is not for people with diabetic ketoacidosis (increased ketones
    in blood or urine).
  oIt is not known if INVOKANA^® is safe and effective in children under
    18years of age.


INVOKANA^® can cause important side effects, including:

  oDehydration. INVOKANA^® can cause some people to have dehydration (the
    loss of body water and salt). Dehydration may cause you to feel dizzy,
    faint, lightheaded, or weak, especially when you stand up (orthostatic

You may be at higher risk of dehydration if you:

     ohave low blood pressure
     otake medicines to lower your blood pressure, including diuretics (water
     oare on low sodium (salt) diet
     ohave kidney problems
     oare 65 years of age or older

  oVaginal yeast infection. Women who take INVOKANA^® may get vaginal yeast
    infections. Symptoms of a vaginal yeast infection include:

       ovaginal odor
       owhite or yellowish vaginal discharge (discharge may be lumpy or look
         like cottage cheese)
       ovaginal itching

  oYeast infection of the penis (balanitis or balanoposthitis). Men who take
    INVOKANA^® may get a yeast infection of the skin around the penis. Certain
    men who are not circumcised may have swelling of the penis that makes it
    difficult to pull back the skin around the tip of the penis. Other
    symptoms of yeast infection of the penis include:

       oredness, itching, or swelling of the penis
       orash of the penis
       ofoul smelling discharge from the penis
       opain 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. Your doctor may suggest you use an over-the-counter
antifungal medicine. Talk to your doctor right away if you use an
over-the-counter antifungal medication and your symptoms do not go away.

Do not take INVOKANA^® if you:

  oare allergic to canagliflozin or any of the ingredients in INVOKANA^®. See
    the end of the Medication Guide for a list of ingredients in INVOKANA^®.
    Symptoms of allergic reaction to INVOKANA^® may include:

       oraised red patches on your skin (hives)
       oswelling of the face, lips, tongue, and throat that may cause
         difficulty in breathing or swallowing

  ohave severe kidney problems or are on dialysis

Before you take INVOKANA^®, tell your doctor if you:

  ohave kidney problems
  ohave liver problems
  oare on a low sodium (salt) diet. Your doctor may change your diet or your
    dose of INVOKANA^®.
  ohave ever had an allergic reaction to INVOKANA^®
  ohave other medical conditions
  oare pregnant or plan to become pregnant. It is not known if INVOKANA^®
    will harm your unborn baby. If you are pregnant, talk with your doctor
    about the best way to control your blood sugar while you are pregnant.
  oare breastfeeding or plan to breastfeed. It is not known if INVOKANA^®
    passes into your breast milk. Talk with your doctor about the best way to
    feed your baby if you are taking INVOKANA^®.

Tell your doctor about all the medicines you take, including prescription and
non-prescription medicines, vitamins, and herbal supplements.

INVOKANA^® may affect the way other medicines work, and other medicines may
affect how INVOKANA^® works. Especially tell your doctor if you take:

  odiuretics (water pills)
  orifampin (used to treat or prevent tuberculosis)
  ophenytoin or phenobarbital (used to control seizures)
  oritonavir (Norvir®, Kaletra®, Lopinavir ®)* (used to treat HIV infection)
  odigoxin (Lanoxin®)* (used to treat heart problems)

Ask your doctor or pharmacist for a list of these medicines if you are not
sure if your medicine is listed above.

Know the medicines you take. Keep a list of them and show it to your doctor
and pharmacist when you get a new medicine.


  oTake INVOKANA^® by mouth 1time each day exactly as your doctor tells you
    to take it.
  oYour doctor will tell you how much INVOKANA^® to take and when to take it.
    Your doctor may change your dose if needed.
  oIt is best to take INVOKANA^® before the first meal of the day.
  oYour doctor may tell you to take INVOKANA^® along with other diabetes
    medicines. Low blood sugar can happen more often when INVOKANA^® is taken
    with certain other diabetes medicines. See "What are the possible side
    effects of INVOKANA^®?"
  oIf you miss a dose, take it as soon as you remember. If it is almost time
    for your next dose, skip the missed dose and take the medicine at the next
    regularly scheduled time. Do not take two doses of INVOKANA^® at the same
    time. Talk to your doctor if you have questions about a missed dose.
  oIf you take too much INVOKANA^®, call your doctor or go to the nearest
    hospital emergency room right away. When your body is under some types of
    stress, such as fever, trauma (such as a car accident), infection, or
    surgery, the amount of diabetes medicine you need may change. Tell your
    doctor right away if you have any of these conditions and follow your
    doctor's instructions.
  oStay on your prescribed diet and exercise program while taking INVOKANA^®.
  oCheck your blood sugar as your doctor tells you to.
  oINVOKANA^® will cause your urine to test positive for glucose.
  oYour doctor may do certain blood tests before you start INVOKANA^® and
    during treatment as needed. Your doctor may change your dose of INVOKANA^®
    based on the results of your blood tests.
  oYour doctor will check your diabetes with regular blood tests, including
    your blood sugar levels and your hemoglobin A1C.

INVOKANA^® may cause serious side effects, including:
See "What is the most important information I should know about INVOKANA^®?"

  okidney problems
  oa high amount of potassium in your blood (hyperkalemia)
  olow 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

Signs and symptoms of low blood sugar may include:

  ofast heartbeat
  oshaking or feeling jittery
  oserious 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. See "Who should not take
    INVOKANA^®?". Your doctor may give you a medicine for your allergic
    reaction and prescribe a different medicine for your diabetes.

The most common side effects of INVOKANA^® include:

  ovaginal yeast infections and yeast infections of the penis (See "What is
    the most important information I should know about INVOKANA^®?")
  ourinary tract infection
  ochanges 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. These are not all the possible side effects of INVOKANA^®. For more
information, ask your doctor or pharmacist.

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

Please see the full Prescribing Information and Medication Guide.

Trademarks are those of their respective owners.

About Janssen Research & Development, LLC
At Janssen, we are dedicated to addressing and solving some of the most
important unmet medical needs of our time in oncology, immunology,
neuroscience, infectious diseases and vaccines, 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. Janssen Research & Development, LLC and Janssen
Pharmaceuticals, Inc. are part of the Janssen Pharmaceutical Companies of
Johnson & Johnson. Please visit http://www.janssenrnd.com for more

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, any of the other Janssen Pharmaceutical Companies 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 health care 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 health care
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 December 30,
2012. Copies of this Form 10-K, as well as subsequent 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 statements as a result of new information or future
events or developments.

SOURCE Janssen Research & Development, LLC

Website: http://www.janssenrnd.com
Contact: Media Inquiries: Christina Holden, 908-927-3581 office, 201-650-2355
cell, cholden7@its.jnj.com or Christina Chan, 908-927-5769 office,
908-635-2406 cell, cchan20@its.jnj.com; Investor Relations: Stan Panasewicz,
732-524-2524 office or Louise Mehrotra, 732-524-6491 office
Press spacebar to pause and continue. Press esc to stop.