Phase 3 Results Show Canagliflozin as Add-On Therapy to Metformin and Pioglitazone Significantly Lowers Blood Sugar Levels in Adult Patients with Type 2 Diabetes

Update: Invokana (canagliflozin) Now FDA Approved - March 29, 2013

BARCELONA, November 9, 2012 — Janssen Research & Development, LLC (Janssen) today announced that its investigational medicine canagliflozin substantially lowered blood glucose levels compared to placebo when used as add-on therapy in patients with type 2 diabetes who are inadequately controlled with the antihyperglycemic medications metformin and pioglitazone. These results were presented at the 4th World Congress on Controversies to Consensus in Diabetes, Obesity, and Hypertension (CODHy).

The data presented are the latest Phase 3 results for canagliflozin, which is being evaluated across a spectrum of patients with type 2 diabetes. Results from the study (known as DIA3012) showed that canagliflozin, dosed once daily at 100 mg or 300 mg in addition to metformin and pioglitazone, had statistically greater A1C reductions at 26 weeks relative to placebo (change from baseline, -0.89% and -1.03%, vs. -0.26%, respectively, p<0.001). The overall incidence of adverse events (AEs) was generally similar across all treatment arms.

“Given the global diabetes epidemic and the significant burden faced by patients who suffer from uncontrolled diabetes, it is critical that we evaluate new therapies in combination with existing antihyperglycemic therapies,” said Dr. Thomas Forst, lead investigator on the study from the University of Mainz in Mainz, Germany. “The efficacy and safety profile for canagliflozin in this trial is encouraging. This data combined with other results seen to date, show that canagliflozin may provide added benefit in managing important diabetes parameters when used alone or in addition to existing diabetes treatments."

In secondary efficacy endpoint measures of the study, both the canagliflozin 100 mg and 300 mg dose groups provided reductions in body weight compared to placebo (-2.8% and -3.8% vs. -0.1%, respectively, p<0.001) and reductions in systolic blood pressure (-5.3 mmHg, p<0.01 and -4.7 mmHg, p<0.05, vs. -1.2 mmHg, respectively). Reductions in fasting plasma glucose were consistent with the primary endpoint for canagliflozin 100 mg and 300 mg, compared to placebo (-1.49 and -1.84 mmol/L vs. 0.14 mmol/L, respectively, p<0.001). Increases in high-density lipoprotein cholesterol were observed with canagliflozin 100 mg and 300 mg, compared to placebo [7.2% (0.08 mmol/L), p<0.05, and 8.9% (0.10 mmol/L), p<0.001, vs. 2.4% (0.02 mmol/L), respectively], and increases in low-density lipoprotein cholesterol were also seen [7.1% (0.08 mmol/L) and 11.3% (0.19 mmol/L) vs. -0.4% (-0.10 mmol/L), respectively]. Canagliflozin decreased triglyceride levels at the 300 mg dose [-1.7% (-0.16 mmol/L), p<0.01)].  Triglyceride levels increased at the 100 mg dose [3.1% (-0.06 mmol/L), p=ns)], though placebo was associated with a higher increase [15.3% (0.10 mmol/L)].

The incidence of AEs leading to discontinuation was low and similar across treatment groups (3.5% for canagliflozin total and 5.2% for placebo). Most AEs were assessed by the investigator as mild to moderate in intensity, and the overall incidence of AEs was balanced across treatment arms. Adverse events of genital mycotic infections in men and women, and increased frequency of urination (pollakiuria) were more common with canagliflozin 100 mg and 300 mg compared to placebo in men and women; these specific adverse events were generally mild or moderate in intensity and did not lead to discontinuation. Rates of urinary tract infections and hypoglycemia were low and similar across groups.

These data were included in the New Drug Application (NDA) Janssen submitted to the U.S. Food and Drug Administration and the Marketing Authorization Application (MAA) submitted to the European Medicines Agency seeking approval for the use of canagliflozin for the treatment of type 2 diabetes announced on May 31, 2012 and June 26, 2012, respectively.

“This is an exciting new area of research, and these results further support the efficacy and safety profile of canagliflozin,” said Kirk Ways, M.D., Ph.D., Vice President and Compound Development Team Leader for canagliflozin at Janssen. “The data are in line with the Phase 3 results announced earlier this year at the annual meetings of the American Diabetes Association and European Association for the Study of Diabetes which suggest that canagliflozin could help control blood glucose in a wide range of patients with type 2 diabetes, including patients on other antihyperglycemic medications such as pioglitazone and metformin.”

These results are included in the abstract, “Efficacy and Safety of Canagliflozin in Subjects with Type 2 Diabetes on Metformin and Pioglitazone” (board #64). An additional abstract, “Efficacy and Safety of Canagliflozin in Subjects with Type 2 Diabetes with Moderate Renal Impairment” (board #75) will also be presented at CODHy 2012.

About Canagliflozin
Canagliflozin is an investigational sodium glucose co-transporter 2 (SGLT2) inhibitor for the treatment of patients with type 2 diabetes. The kidneys of people with type 2 diabetes reabsorb greater amounts of glucose back into the body compared to non-diabetic people, which may contribute to elevated glucose levels. Canagliflozin blocks the reabsorption of glucose by the kidney, increasing glucose excretion and lowering blood glucose levels.

The global Phase 3 canagliflozin clinical program, which enrolled 10,285 patients in nine studies, is the largest late-stage development program for an investigational pharmacologic product for the treatment of type 2 diabetes submitted to health authorities to date. The program evaluated the safety and efficacy of canagliflozin across the spectrum of type 2 diabetes management, from adult patients treated only with diet and exercise to those requiring insulin injections to maintain glycemic control, and in three large studies in special populations: older patients with type 2 diabetes, patients with type 2 diabetes who have had moderate renal impairment, and patients with type 2 diabetes who had or were at high risk for developing cardiovascular disease.

Janssen and its affiliates have rights to canagliflozin through a license agreement with Mitsubishi Tanabe Pharma Corporation. Janssen Pharmaceuticals, Inc. and its affiliates have marketing rights in North America, South America, Europe, Middle East, Africa, Australia, New Zealand, and parts of Asia.

About Janssen
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 information.

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(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 healthcare 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 healthcare 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 January 1, 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 nor Johnson & Johnson undertake to update any forward-looking statements as a result of new information or future events or developments).

Media contacts:
Ernie Knewitz
Phone: (908) 927-2953
eknewitz@its.jnj.com

Christina Chan
Phone: (908) 927-5769
cchan20@its.jnj.com

Investor contacts:
Stan Panasewicz
Phone: (732) 524-2524

Louise Mehrotra
Phone: (732) 524-6491
 

Posted: November 2012

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