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Merck's Omarigliptin, an Investigational Once-Weekly DPP-4 Inhibitor, Achieved Similar A1C Reductions to JANUVIA® (sitagliptin) in Patients with Type 2 Diabetes Inadequately Controlled on Metformin Monotherapy

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KENILWORTH, N.J.--(BUSINESS WIRE)--

Merck (NYSE: MRK), known as MSD outside the United States and Canada, today announced that omarigliptin, Merck's investigational once-weekly DPP-4 inhibitor in development for adults with type 2 diabetes, achieved its primary efficacy endpoint in a Phase 3 study. Omarigliptin was found to be non-inferior to Merck's once-daily DPP-4 inhibitor, JANUVIA® (sitagliptin), at reducing patients' A1C* levels from baseline, with similar A1C reductions achieved in both groups. The head-to-head study was designed to evaluate once-weekly treatment with omarigliptin 25 mg compared to 100 mg of JANUVIA once daily, a widely prescribed DPP-4 inhibitor worldwide. Results were presented during an oral session at the 51st European Association for the Study of Diabetes (EASD) Annual Meeting.

"Type 2 diabetes is a chronic, progressive disease that affects millions of Americans2, and its prevalence continues to grow rapidly. Many people are still not at their recommended blood sugar levels, underscoring the importance of individualized blood sugar goals and multiple treatment options," said Sam Engel, M.D., associate vice president, Merck clinical research, diabetes and endocrinology. "Omarigliptin has the potential to be an important treatment option, particularly for those who also prefer once-weekly dosing."

Merck submitted a new drug application to the Japanese Pharmaceuticals and Medical Devices Agency in November 2014 and plans to submit for regulatory approval of omarigliptin in the U.S. by the end of 2015. The clinical development program for omarigliptin, O-QWEST (Omarigliptin Q Weekly Efficacy and Safety in Type 2 Diabetes), includes 10 Phase 3 clinical trials involving approximately 8,000 patients with type 2 diabetes.

About the study

This Phase 3 randomized, double-blind, non-inferiority trial assessed the efficacy, safety and tolerability of omarigliptin 25 mg once weekly compared to JANUVIA 100 mg once daily in adults with type 2 diabetes (n=642) who experienced inadequate glycemic control while taking metformin. The primary efficacy endpoint was non-inferiority of omarigliptin to JANUVIA in decreasing A1C levels from baseline to week 24.1 At the start of the trial, baseline A1C was approximately 7.5 percent in both groups. Mean baseline fasting plasma glucose (FPG) levels were also similar between treatment groups.

The study achieved its primary efficacy endpoint of non-inferior reductions in A1C for omarigliptin compared to JANUVIA at 24 weeks.1 At week 24, patients taking omarigliptin had an average A1C reduction from baseline of -0.47 percent as compared to an average reduction of -0.43 percent among patients taking JANUVIA, with a difference of -0.03 between groups (95% CI [-0.15, 0.08]). In patients in the pre-specified sub-group with a higher baseline A1C of greater than or equal to 8.0 percent, omarigliptin treatment resulted in reductions of -0.79 percent compared to -0.71 percent for JANUVIA (difference = -0.08 percent; 95% CI [-0.37, 0.21]).

The percentage of patients achieving their A1C goals was similar for both omarigliptin and JANUVIA. At 24 weeks, 51 percent of patients treated with omarigliptin reached an A1C of less than 7.0 percent, compared to 49 percent of patients treated with JANUVIA (p=0.334). The percentage of patients reaching an A1C of less than 6.5 percent was also similar across treatment groups: 27 percent for omarigliptin compared with 23 percent for JANUVIA (p=0.219). FPG was reduced from baseline by 0.8 mmol/L in the omarigliptin group and 0.5 mmol/L in the JANUVIA group, with a between-group difference of -0.2 mmol/L (p= 0.089).1

The incidences of serious adverse events, drug-related adverse events and discontinuations were similar across both treatment groups. Common adverse events included diarrhea (0.9 percent for omarigliptin vs. 2.8 percent for JANUVIA), influenza (0.3 percent for omarigliptin vs. 2.2 percent for JANUVIA), upper respiratory tract infection (4.0 percent for omarigliptin vs. 3.8 percent for JANUVIA), urinary tract infection (1.2 percent for omarigliptin vs. 2.8 percent for JANUVIA), lipase increase (2.5 percent for omarigliptin vs. 4.1 percent for JANUVIA) and back pain (2.5 percent for omarigliptin vs. 0.6 percent for JANUVIA). Adverse events of hypoglycemia (symptomatic and asymptomatic) were reported in 3.7 percent of the omarigliptin group (with one severe hypoglycemia event reported) and 4.7 percent of the JANUVIA group.1

Indications and Limitations of Use for JANUVIA® (sitagliptin) 25 mg, 50 mg and 100 mg tablets

JANUVIA is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. JANUVIA should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis. JANUVIA has not been studied in patients with a history of pancreatitis. It is unknown whether patients with a history of pancreatitis are at increased risk of developing pancreatitis while taking JANUVIA.

Selected Important Risk Information about JANUVIA

JANUVIA is contraindicated in patients with a history of a serious hypersensitivity reaction to sitagliptin, such as anaphylaxis or angioedema.

There have been postmarketing reports of acute pancreatitis, including fatal and nonfatal hemorrhagic or necrotizing pancreatitis, in patients taking JANUVIA. After initiating JANUVIA, observe patients carefully for signs and symptoms of pancreatitis. If pancreatitis is suspected, promptly discontinue JANUVIA and initiate appropriate management. It is unknown whether patients with a history of pancreatitis are at increased risk of developing pancreatitis while taking JANUVIA.

Assessment of renal function is recommended prior to initiating JANUVIA and periodically thereafter. A dosage adjustment is recommended in patients with moderate or severe renal insufficiency and in patients with end-stage renal disease requiring hemodialysis or peritoneal dialysis. Caution should be used to ensure that the correct dose of JANUVIA is prescribed.

There have been postmarketing reports of worsening renal function, including acute renal failure, sometimes requiring dialysis. A subset of these reports involved patients with renal insufficiency, some of whom were prescribed inappropriate doses of sitagliptin.

When JANUVIA was used in combination with a sulfonylurea or insulin, medications known to cause hypoglycemia, the incidence of hypoglycemia was increased over that of placebo. Therefore, a lower dose of sulfonylurea or insulin may be required to reduce the risk of hypoglycemia.

The incidence (and rate) of hypoglycemia based on all reports of symptomatic hypoglycemia were: 12.2% (0.59 episodes/patient-year) for JANUVIA 100 mg in combination with glimepiride (with or without metformin), 1.8% (0.24 episodes/patient-year) for placebo in combination with glimepiride (with or without metformin), 15.5% (1.06 episodes/patient-year) for JANUVIA 100 mg in combination with insulin (with or without metformin), and 7.8% (0.51 episodes/patient-year) for placebo in combination with insulin (with or without metformin).

There have been postmarketing reports of serious hypersensitivity reactions in patients treated with JANUVIA, such as anaphylaxis, angioedema, and exfoliative skin conditions including Stevens -Johnson syndrome. Onset of these reactions occurred within the first 3 months after initiation of treatment with JANUVIA, with some reports occurring after the first dose. If a hypersensitivity reaction is suspected, discontinue JANUVIA, assess for other potential causes for the event, and institute alternative treatment for diabetes.

Angioedema has also been reported with other dipeptidyl peptidase-4 (DPP-4) inhibitors. Use caution in a patient with a history of angioedema with another DPP-4 inhibitor because it is unknown whether such patients will be predisposed to angioedema with JANUVIA.

There have been postmarketing reports of severe and disabling arthralgia in patients taking DPP-4 inhibitors. The time to onset of symptoms following initiation of drug therapy varied from 1 day to years. Patients experienced relief of symptoms upon discontinuation of the medication. A subset of patients experienced a recurrence of symptoms when restarting the same drug or a different DPP-4 inhibitor. Consider DPP-4 inhibitors as a possible cause for severe joint pain and discontinue drug if appropriate.

There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with JANUVIA or with any other antidiabetic drug.

In clinical studies, the adverse reactions reported, regardless of investigator assessment of causality, in ≥5% of patients treated with JANUVIA as monotherapy and in combination therapy and more commonly than in patients treated with placebo, were upper respiratory tract infection, nasopharyngitis, and headache.

Merck commitment to diabetes

At Merck, we are committed to improving type 2 diabetes care through scientific advancement and innovation for the millions of people living with diabetes every day. We strive to deliver a broad range of treatments and educational tools for patients and healthcare providers and are applying significant resources and capabilities with a continued focus on research and development.

About Merck

Today's Merck is a global healthcare leader working to help the world be well. Merck is known as Merck outside the United States and Canada. Through our prescription medicines, vaccines, biologic therapies, and animal health products, we work with customers and operate in more than 140 countries to deliver innovative health solutions. We also demonstrate our commitment to increasing access to healthcare through far-reaching policies, programs and partnerships. For more information, visit www.merck.com and connect with us on Twitter, Facebook and YouTube.

Forward-Looking Statement of Merck & Co., Inc., Kenilworth, N.J., USA

This news release of Merck & Co., Inc., Kenilworth, NJ, USA (the "company") includes "forward-looking statements" within the meaning of the safe harbor provisions of the United States Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of the Company's management and are subject to significant risks and uncertainties. There can be no guarantees with respect to pipeline products that the products will receive the necessary regulatory approvals or that they will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements.

Risks and uncertainties include, but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of pharmaceutical industry regulation and healthcare legislation in the United States and internationally; global trends toward healthcare cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; the Company's ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of the Company's s patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions.

The Company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in the Company's 2014 Annual Report on Form 10-K and the company's other filings with the Securities and Exchange Commission (SEC) available at the SEC's Internet site (www.sec.gov).

Please see Prescribing Information for JANUVIA® (sitagliptin) at http://www.merck.com/product/usa/pi_circulars/j/januvia/januvia_pi.pdf and Medication Guide for JANUVIA at http://www.merck.com/product/usa/pi_circulars/j/januvia/januvia_mg.pdf.

References

1 Gantz, I et al. Omarigliptin, a once-weekly DPP-4 inhibitor, provides similar glycaemic control to sitagliptin in patients with type 2 diabetes mellitus inadequately controlled on metformin. Presentation #110, to be presented at the 51st EASD Annual Meeting on Sept. 16, 2015. Available at http://www.easdvirtualmeeting.org/resources/omarigliptin-a-once-weekly-dpp-4-inhibitor-provides-similar-glycaemic-control-to-sitagliptin-in-patients-with-type-2-diabetes-mellitus-inadequately-controlled-on-metformin--2. Last accessed Sept. 2015.

2 Centers for Disease Control and Prevention. National Diabetes Statistics Report: Estimates of Diabetes and Its Burden in the United States, 2014. Atlanta, GA: US Department of Health and Human Services; 2014;1–9.

* A1C is an estimate of a person's average blood glucose over a two- to three-month period.

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