FDA Accepts Two Supplemental New Drug Applications to Expand the U.S. Labeling for JANUVIA™
Action Expected by Mid-October on New Indications for First and Only DPP-4 Inhibitor
WHITEHOUSE STATION, N.J., Feb. 15, 2007 - Merck & Co., Inc. today announced that the U.S. Food and Drug Administration (FDA) has accepted for standard review two supplemental New Drug Applications (sNDAs) for JANUVIA™ (sitagliptin), and the Company expects FDA action on both sNDAs by mid-October.
One sNDA is filed in support of a proposed new indication for the use of JANUVIA, as an adjunct to diet and exercise, in combination with metformin as initial therapy to improve glycemic control. The other sNDA is filed in support of two proposed new indications for use of JANUVIA, as an adjunct to diet and exercise, as add-on therapy to a sulfonylurea when the single agent alone does not provide adequate glycemic control and as add-on therapy to the combination of a sulfonylurea plus metformin when dual therapy does not provide adequate glycemic control.
JANUVIA is currently indicated for use as monotherapy and as add-on therapy to either of two other types of oral diabetes medications, metformin or thiazolidinediones (TZDs), to improve blood sugar (glucose) control in patients with type 2 diabetes when diet and exercise are not enough. The recommended dose of JANUVIA is 100 mg once daily. JANUVIA should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis, as it would not be effective in these settings. In clinical trials, JANUVIA demonstrated an overall incidence of side effects comparable to placebo. The most common side effects reported with JANUVIA (greater than or equal to 5 percent and higher than placebo) were stuffy or runny nose and sore throat, upper respiratory infection, and headache.
“If these sNDAs are approved, the expanded labeling will include indications for use of JANUVIA as initial therapy with metformin and as add-on to any of the three most commonly prescribed classes of oral antihyperglycemic agents,” said John Amatruda, M.D., vice president, clinical research, Merck & Co., Inc. “These data further support the broad utility of JANUVIA as an important treatment option for patients with type 2 diabetes.”
Phase III data supporting two sNDAs
The proposed new indication of JANUVIA in combination with metformin as initial therapy is supported by a 24-week, factorial study in 1,091 randomized patients with type 2 diabetes. Results of this study were presented for the first time at the annual meeting of the European Association for the Study of Diabetes in September 2006.
The study showed a significant mean placebo-subtracted reduction in A1C1 of 2.1 percent from a mean baseline A1C of 8.7 percent (primary analysis of all patients treated, p >0.001) in the patients treated with JANUVIA 50 mg twice daily combined with metformin 1,000 mg twice daily (n=178). In the same study, 66 percent of patients treated with JANUVIA 50 mg twice daily combined with metformin 1,000 mg twice daily achieved goal A1C levels of <7 percent compared to 38 percent of patients treated with metformin 1,000 mg twice daily alone (p <0.01). Even in those patients receiving a lower dose of metformin (JANUVIA 50 mg twice daily and metformin 500 mg twice daily, n=183), significant A1C placebo-subtracted reductions (1.6 percent, p <0.001) and greater goal attainment (43 percent vs. 23 percent with metformin 500 mg twice daily alone, p <0.01) were observed.
In the study, initial therapy of JANUVIA and metformin was generally well tolerated and showed no meaningful differences in tolerability compared to metformin alone. Side effects of JANUVIA 50 mg twice daily and metformin 1,000 mg twice daily compared to metformin 1,000 mg twice daily alone included diarrhea (9 percent vs. 10 percent, respectively), nausea (6 percent vs. 8 percent), abdominal pain/discomfort (3 percent vs. 5 percent) and vomiting (3 percent vs. 1 percent).
The proposed new indications of adding JANUVIA to a sulfonylurea or to a sulfonylurea plus metformin are supported by a 24-week study examining the efficacy and safety of JANUVIA in 441 patients with type 2 diabetes who had inadequate glycemic control on a sulfonylurea alone or a sulfonylurea plus metformin. Results from this Phase III study were submitted to a major medical meeting for presentation later this year.
Dosing of JANUVIA
The recommended dose of JANUVIA is 100 mg once daily, with or without food, for all approved indications. No dosage adjustment is needed for patients with mild to moderate hepatic insufficiency or in patients with mild renal insufficiency (CrCl greater than or equal to 50 mL/min). To achieve plasma concentrations of JANUVIA similar to those in patients with normal renal function, lower dosages are recommended in patients with moderate and severe renal insufficiency as well as in ESRD patients requiring hemodialysis. For patients with moderate renal insufficiency (CrCl greater than or equal to 30 to < 50 mL/min), the dose of JANUVIA is 50 mg once daily. For those with severe renal insufficiency (CrCl < 30 mL/min) or with ESRD requiring dialysis, the dose of JANUVIA is 25 mg once daily. Because there is a need for dosage adjustment based upon renal function, assessment of renal function is recommended prior to initiation of JANUVIA and periodically thereafter.
Selected cautionary information
JANUVIA should be used during pregnancy only if clearly needed. Caution should be exercised when JANUVIA is administered to a nursing woman. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection in the elderly and it may be useful to assess renal function in these patients prior to initiating dosing and periodically thereafter. The incidence of selected gastrointestinal adverse reactions in patients treated with JANUVIA was as follows: abdominal pain (JANUVIA, 2.3 percent; placebo, 2.1 percent), nausea (1.4 percent, 0.6 percent) and diarrhea (3.0 percent, 2.3 percent).
Expanding clinical trial program for JANUVIA
Merck’s clinical development program for JANUVIA is robust and continues to expand with 43 studies completed or under way, and ten more studies set to begin this year. There are more than 7,600 patients in the Company’s clinical studies with about 4,700 of these patients being treated with JANUVIA. Additionally, about 1,100 patients have been treated with JANUVIA for more than a year.
Merck & Co., Inc. is a global research-driven pharmaceutical company dedicated to putting patients first. Established in 1891, Merck discovers, develops, manufactures and markets vaccines and medicines to address unmet medical needs. The company devotes extensive efforts to increase access to medicines through far-reaching programs that not only donate Merck medicines but help deliver them to the people who need them. Merck also publishes unbiased health information as a not-for-profit service. For more information, visit www.merck.com.
Merck forward-looking statement
This press release contains “forward-looking statements” as that term is defined in the Private Securities Litigation Reform Act of 1995. These statements are based on management’s current expectations and involve risks and uncertainties, which may cause results to differ materially from those set forth in the statements. The forward-looking statements may include statements regarding product development, product potential or financial performance. No forward-looking statement can be guaranteed, and actual results may differ materially from those projected. Merck undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise. Forward-looking statements in this press release should be evaluated together with the many uncertainties that affect Merck’s business, particularly those mentioned in the cautionary statements in Item 1 of Merck’s Form 10-K for the year ended Dec. 31, 2005, and in its periodic reports on Form 10-Q and Form 8-K, which the Company incorporates by reference.
JANUVIA™ is a registered trademark for Merck & Co., Inc.
1A1C is a measure of a person’s average blood glucose over a two- to three-month period.
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