Real-World Study Shows INVOKANA® (canagliflozin) 300mg Demonstrates Better Blood Glucose Control Than Farxiga® (dapagliflozin) 10mg in Patients with Type 2 Diabetes

First Real-World Study Comparing Sodium Glucose Cotransporter 2 Inhibitor (SGLT2i) Therapies Also Showed Patients Taking INVOKANA^® 300mg Were Significantly Less Likely to Discontinue Treatment or Switch to Another Diabetes Medicine

TITUSVILLE, NJ, April 27, 2018 – The Janssen Pharmaceutical Companies of Johnson & Johnson today announced the results of a real-world study showing that adults with type 2 diabetes initiated on INVOKANA^® (canagliflozin) 300mg had significantly better blood glucose control, based on A1C goal attainment and reduction, compared to similar patients initiated on Farxiga^® (dapagliflozin) 10mg. Patients on INVOKANA^® were also less likely to discontinue treatment or switch to another medicine to treat their type 2 diabetes. Findings were recently published in Current Medical Research and Opinion.

“Controlling blood glucose levels is central to diabetes treatment because it can reduce the risk of diabetes-related complications, such as kidney disease, retinopathy and potentially cardiovascular disease,”^[1],[2] said Lawrence Blonde, MD, Director, Ochsner Diabetes Clinical Research Unit, Frank Riddick Diabetes Institute, Department of Endocrinology, Diabetes and Metabolism, Ochsner Medical Center, New Orleans, Louisiana. “This first real-world analysis comparing SGLT2i therapies in adults with type 2 diabetes showed that canagliflozin (INVOKANA^®) 300mg each day allowed more patients to achieve blood glucose control [A1C <7%] than did a daily dose of dapagliflozin (Farxiga^®) 10mg.”

Up to half of patients with type 2 diabetes do not meet individualized targets for blood glucose control, measured by hemoglobin A1C, which reflects a person’s average blood glucose over the past two to three months.^[3] The Healthcare Effectiveness Data and Information Set (HEDIS) recommends an A1C of less than 8.0 percent as a goal for most people with type 2 diabetes,^[4] while the American Diabetes Association (ADA) recommends less than 7.0 percent.^[5]

In the analysis, which matched INVOKANA^® and dapagliflozin patients based on demographic and clinical characteristics including A1C, a significantly greater proportion of INVOKANA^® patients achieved the HEDIS A1C goal of less than 8.0 percent (70.8 vs. 59.1 percent, p=0.0001), as well as the ADA goal of less than 7.0 percent (36.7 vs. 25.1 percent, p<0.0001).

“These findings are an important addition to the large and growing body of real-world evidence supporting INVOKANA^®,” said Paul Burton, MD, PhD, FACC, Vice President, Medical Affairs, Janssen Pharmaceuticals, Inc. “Because the significant benefits of INVOKANA^® shown in this study were based on data from everyday clinical practice, they are especially relevant for physicians to consider when choosing an SGLT2i therapy for their patients.”

Study and Findings

The analysis was based on Optum Clinformatics™ claims data and looked at 558 INVOKANA^® patients and an equal number of matched dapagliflozin patients, beginning 12 months before initiating the medications until six months afterwards. The primary outcome was the proportion of patients who achieved the HEDIS-recommended A1C goal of less than 8.0 percent. Secondary outcomes included the proportion of patients who achieved the ADA-recommended A1C goal of less than 7.0 percent, the proportion of patients with A1C greater than 9.0 percent (poor control of type 2 diabetes, as defined by HEDIS), the absolute change in A1C, and treatment patterns indicative of adherence. Analyzing data at six months after patients initiated the medications, the investigators found:

• Patients on INVOKANA^® 300mg had a 29 percent greater reduction in A1C compared to patients initiated on dapagliflozin 10mg.

• A significantly higher proportion of INVOKANA^® patients than dapagliflozin patients achieved A1C less than 8.0 percent (primary endpoint): 70.8 percent vs. 59.1 percent; odds ratio (OR) 1.60, 95 percent confidence interval (CI): 1.26, 2.04; p=0.0001.

• A significantly higher proportion of INVOKANA^® patients than dapagliflozin patients achieved A1C less than 7.0 percent: 36.7 percent vs. 25.1 percent; OR 1.75, CI: 1.34, 2.27; p<0.0001.

• Average A1C levels were significantly lower in INVOKANA^® vs. dapagliflozin patients: 7.57 percent vs. 7.85 percent, difference of -0.28 percent; p=0.0003.

• Average A1C reduction was significantly greater in INVOKANA^® vs. dapagliflozin patients: 1.17 percent vs. 0.91 percent, difference of -0.26 percent; p=0.0049.

• A similar proportion of INVOKANA^® and dapagliflozin patients had A1C levels above 9.0 percent (12.0 percent vs. 15.1 percent; OR 0.77, CI: 0.55, 1.09; p=0.1386).

• INVOKANA^® patients were significantly less likely than dapagliflozin patients to discontinue treatment (OR 0.75, CI: 0.57, 0.99; p=0.0400) or switch medication (OR 0.72, CI: 0.54, 0.96; p=0.0229), and approximately as likely to have add-on therapy (OR 1.30, CI: 0.96, 1.74; p=0.0865).

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 and/or safety of a treatment.

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.

Janssen Pharmaceuticals, Inc. and its affiliates have rights to canagliflozin through a license agreement with Mitsubishi Tanabe Pharma Corporation, including in the United States.

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^®.

Canagliflozin is licensed from Mitsubishi Tanabe Pharma Corporation.

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. is part of the Janssen Pharmaceutical Companies of Johnson & Johnson.

Cautions Concerning Forward-Looking Statements

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 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 Research & Development, 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] American Diabetes Association. Standards of medical care in diabetes - 2018. Diabetes Care. 2018;41(suppl 1):S1-S159.
^[2] Garber AJ, Abrahamson MJ, Barzilay JI, et al. Consensus statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the comprehensive type 2 diabetes management algorithm – 2018 executive summary. Endocr Pract 2018;24(1):91-120.
^[3] Ali MK, Bullard KM, Saaddine JB, et al. Achievement of goals in U.S. diabetes care, 1999-2010. N Engl J Med 2013;368:1613-24.
^[4] NCQA (National Committee for Quality Assurance). Comprehensive diabetes care: the HEDIS (Healthcare Effectiveness Data and Information Set) measures. Available at: http://www.ncqa.org/report-cards/health-plans/state-of-health-care-quality/2017-table-of-contents/diabetes-care. Accessed February 12, 2018.
^[5] American Diabetes Association. Standards of medical care in diabetes - 2018. Diabetes Care. 2018;41(suppl 1):S1-S159.