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FDA Approves Invokamet XR

FDA Approves Invokamet XR (Canagliflozin/Metformin Hydrochloride Extended-Release) for the Treatment of Adults with Type 2 Diabetes

RARITAN, N.J., September 21, 2016 – Janssen Pharmaceuticals, Inc. (Janssen) announced today the U.S. Food and Drug Administration (FDA) has approved Invokamet XR - a once-daily, fixed-dose combination therapy of canagliflozin and metformin hydrochloride extended-release (XR)—for first-line use as an adjunct to diet and exercise to improve blood glucose control in adults with type 2 diabetes when treatment with the two medications is appropriate.[1] Invokamet XR combines Invokana (canagliflozin), the most prescribed sodium glucose co-transporter 2 (SGLT2) inhibitor, with more than 9 million U.S. prescriptions since launch,[2] and an XR formulation of metformin. Metformin is commonly prescribed as an initial therapy for the treatment of type 2 diabetes.

“Invokamet XR offers the convenience of once-daily dosing and provides physicians needed flexibility for tailoring treatment to the needs of type 2 diabetes patients, especially those with higher A1C levels,” said John Anderson, M.D.,* Frist Clinic, Nashville, Tenn. “As with Invokamet, physicians can prescribe the XR formulation to adults when they are first diagnosed with type 2 diabetes or as additional therapy for people whose A1C levels are not well controlled with either agent alone.”

Phase 3 studies have shown the combination of Invokana and metformin reduces A1C significantly more than metformin alone, sitagliptin plus metformin, or glimepiride plus metformin. Treatment with Invokana as an add-on to metformin also demonstrated greater reductions in the secondary endpoints of body weight and systolic blood pressure.

The approved indication for Invokamet XR aligns with current type 2 diabetes treatment guidelines from the American Association of Clinical Endocrinologists and American College of Endocrinology and from the American Diabetes Association, which recommend dual therapy for patients with higher A1C levels.[3],[4] Specifically, guidelines recommend dual therapy for patients who have an initial A1C level of 7.5 percent or higher[3] and for those who have an initial level below 7.5 percent and do not achieve an A1C treatment goal after about three months on single therapy, often metformin.4 In addition, dual or triple therapy is recommended as first-line therapy in asymptomatic patients with an initial A1C level above 9 percent.[3]

A1C is a measure of average blood glucose over the past two to three months; the American Diabetes Association recommends most adults with type 2 diabetes maintain A1C levels of 7 percent or less.[5]

“The approval of Invokamet XR is further evidence of our ongoing commitment to provide new treatment options for people with type 2 diabetes,” said Paul Burton, M.D., Ph.D., Vice President, Medical Affairs, Janssen. “Our Invokana portfolio now offers physicians even more choices for helping patients improve control of A1C levels and other important health measures, with numerous dosing options for monotherapy and for combination therapy with both metformin and metformin XR.”

Invokamet XR is available in four dosages, in tablets containing canagliflozin 50 milligrams (mg) or 150 mg, and metformin XR 500 mg or 1000 mg. The recommended dosing is two tablets once daily with the morning meal. The prescribing information for Invokamet XR also contains a boxed warning for lactic acidosis, a rare but serious complication that can occur due to metformin accumulation.[1]

Studies in healthy adults have demonstrated that administration of Invokamet XR results in the same levels of canagliflozin and metformin XR in the body as when corresponding dosages of the two medicines are administered as separate tablets. Canagliflozin works with the kidneys to help adults with type 2 diabetes lose some sugar through the process of urination, and metformin decreases the production of glucose in the liver and improves the body's response to insulin. Invokamet XR should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis.[1]

Invokamet, the first combination of an SGLT2 inhibitor and an immediate-release formulation of metformin available in the United States, was initially approved by FDA in August 2014 as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes not adequately controlled with metformin or canagliflozin, or who are already being treated with both medications separately. In May 2016, FDA expanded the Invokamet indication to include adults with type 2 diabetes who are not already being treated with canagliflozin or metformin and may benefit from dual therapy.[6]

Phase 3 Studies of Canagliflozin-Metformin Therapy

The co-administration of canagliflozin - Invokana - and metformin has been evaluated in seven Phase 3 studies. One study included 1,186 adults with type 2 diabetes inadequately controlled with diet and exercise, and who had not been treated previously with any glucose-lowering medications; the six other studies included 4,732 patients with type 2 diabetes who were already taking glucose-lowering medications. Collectively, the Phase 3 studies showed that the combination of Invokana and metformin lowered blood sugar and, in pre-specified secondary endpoints, was associated with greater reductions in body weight and systolic blood pressure.

The Phase 3 studies also showed that Invokana is generally well-tolerated, and the most common adverse events include genital yeast infections, urinary tract infections, and changes in urination. The most common adverse reactions due to initiation of metformin, as noted in the prescribing information for that medication, are diarrhea, nausea, vomiting, flatulence, asthenia, indigestion, abdominal discomfort, and headache. Hypoglycemia does not occur in patients receiving metformin alone under usual circumstances of use. Invokana can increase the risk of hypoglycemia when combined with insulin or a medication that increases insulin levels (e.g., a sulfonylurea). Therefore, a lower dose of insulin or insulin-raising medication may be required to minimize the risk of hypoglycemia when used in combination with Invokamet XR.

About Type 2 Diabetes

Of the approximately 29 million people who have diabetes in the United States, 90 to 95 percent of them have type 2 diabetes, which is chronic, 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.

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.

*Dr. Anderson was not compensated for any media work. He has been a paid consultant to Janssen Pharmaceuticals, Inc.

Cautions Concerning Forward-Looking Statements

This press release contains "forward-looking statements" as defined in the Private Securities Litigation Reform Act of 1995 regarding treatment options for people with type 2 diabetes. 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 Pharmaceuticals, Inc. 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 obtaining regulatory approvals; uncertainty of commercial success; manufacturing difficulties and delays; competition, including new products and patents attained by competitors; challenges to patents; product efficacy or safety concerns resulting in product recalls or regulatory action; 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 January 3, 2016, including in Exhibit 99 thereto, and the company's subsequent 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] INVOKAMET® XR (canagliflozin and metformin hydrochloride extended release) tablets, for oral use. Prescribing information, 09/2016. Janssen Pharmaceuticals, Inc., Titusville, NJ, 08560.
[2] Data on file. Janssen Pharmaceuticals, Inc. Based on IMS Health, NPA Weekly, Total Prescriptions, April 2013- July 1 2016.
[3] 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 - 2016 EXECUTIVE SUMMARY. Endocr Pract. 2016 Jan;22(1):84-113.
[4] American Diabetes Association. Approaches to glycemic treatment. Sec. 7. In Standards of Medical Care in Diabetesd2016. Diabetes Care 2016;39(Suppl. 1):S52–S59.
[5] American Diabetes Association. Glycemic targets. Sec. 5. In Standards of Medical Care in Diabetes – 2016. Diabetes Care 2016;39(Suppl. 1):S39–S46.
[6] INVOKAMET® (canagliflozin and metformin hydrochloride) tablets, for oral use. Prescribing information, updated 08/2016. Janssen Pharmaceuticals, Inc., Titusville, NJ, 08560.

Source: Janssen Pharmaceuticals, Inc.

Posted: September 2016

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