FDA Approves Steglatro
FDA Approves Steglatro (ertugliflozin) for Type 2 Diabetes
KENILWORTH, N.J. & NEW YORK--(BUSINESS WIRE) December 22, 2017 -- Merck (NYSE:MRK), known as MSD outside the United States and Canada, and Pfizer Inc. (NYSE:PFE), today announced that the U.S. Food and Drug Administration (FDA) has approved Steglatro (ertugliflozin) tablets, an oral sodium-glucose cotransporter 2 (SGLT2) inhibitor indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
Steglatro is not recommended in patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis. Steglatro is contraindicated in patients with severe renal impairment, end-stage renal disease or on dialysis, or with a history of a serious hypersensitivity reaction to ertugliflozin.
This FDA approval is supported by seven Phase 3 studies of approximately 4,800 patients. Steglatro was studied as monotherapy and in combination with metformin and/or sitagliptin, as well as with insulin and a sulfonylurea, in adults with type 2 diabetes and moderate renal impairment. “In clinical trials, treatment with Steglatro resulted in significant A1C reductions when used alone or in combination with sitagliptin,” said Juan Pablo Frias, M.D., president and principal investigator, National Research Institute, Los Angeles. “This is important, as A1C-lowering is a key component of diabetes management, and many of my adult patients may need multiple medications to help manage their condition.”
“Merck welcomes the opportunity to provide adult patients with type 2 diabetes and their physicians these new medicines to help lower A1C, building on over a decade of experience with our diabetes portfolio and reflecting our continued commitment to diabetes research and patient care,” said Keith Kaufman, M.D., vice president, global clinical development and therapeutic area head for diabetes, endocrinology and women’s health, Merck Research Laboratories.
Diabetes is a chronic, progressive disease affecting approximately 30 million Americans (90 to 95 percent have type 2 diabetes). About one-third of adults with type 2 diabetes in the U.S. are not at their A1C goal.
“There remains a need to help adults with type 2 diabetes improve their glycemic control, and as the prevalence of the disease continues to rise, we are pleased to offer additional treatment options to these patients and the healthcare providers who treat them,” said James Rusnak, M.D., Ph.D., senior vice president and chief development officer, internal medicine, Pfizer Global Product Development.
One of the studies supporting the FDA approvals was VERTIS SITA2, a 26-week double-blind, placebo-controlled study. VERTIS SITA2 evaluated Steglatro (ertugliflozin) compared to placebo in 463 patients with type 2 diabetes inadequately controlled (baseline A1C of 7.0-10.5%) on background metformin (≥1,500 mg/day) and sitagliptin (100 mg/day). Patients were randomized to Steglatro 5 mg, Steglatro 15 mg or placebo administered once daily, in addition to continuation of background metformin and sitagliptin therapy. In the study, Steglatro provided significant additional A1C reductions on top of metformin plus sitagliptin of 0.7 percent and 0.8 percent, respectively, for the 5 and 15 mg doses, compared with 0.2 percent for placebo (p<0.001, for both comparisons), which was the study’s primary endpoint.
In this study, Steglatro significantly reduced body weight by 6.6 pounds with the 5 mg dose and 6.2 pounds with the 15 mg dose, on top of metformin plus sitagliptin, compared with 2.2 pounds with placebo. Baseline body weight was 193.1 pounds, 190.9 pounds and 190.6 pounds for the 5 mg, 15 mg and placebo groups, respectively. The difference from placebo was -4.2 pounds for Steglatro 5 mg (95% CI: -5.7, -2.9) and -4.0 pounds for Steglatro 15 mg (95% CI: -5.3, -2.6). Steglatro 5 mg and 15 mg were also associated with significant reductions in fasting plasma glucose (25.7 mg/dL and 32.1 mg/dL, respectively, vs. 6.5 mg/dL for placebo; p<0.001, for both comparisons). Baseline fasting plasma glucose levels were 167.7 mg/dL, 171.7 mg/dL and 169.6 mg/dL for the 5 mg, 15 mg and placebo groups, respectively. Significant reductions in systolic blood pressure were also observed for Steglatro (3.8 mmHg for 5 mg and 4.5 mmHg for 15 mg, vs. 0.2 mmHg for placebo). Baseline systolic blood pressure values were 132.1 mmHg, 131.6 mmHg and 130.2 mmHg for the 5 mg, 15 mg and placebo groups, respectively. For systolic blood pressure, the difference from placebo was -3.7 mmHg for Steglatro (ertugliflozin) 5 mg (95% CI: -6.1, -1.2) and -4.3 mmHg for Steglatro 15 mg (95% CI: -6.7, -1.9). Steglatro is not indicated for weight loss or hypertension.
Steglatro causes intravascular volume contraction. Symptomatic hypotension may occur after initiating Steglatro, particularly in patients with impaired renal function (estimated glomerular filtration rate [eGFR] less than 60 mL/min/1.73 m2), elderly patients (≥65 years), patients with low systolic blood pressure or patients on diuretics. Before initiating Steglatro, volume status should be assessed and corrected if indicated. Monitor for signs and symptoms after initiating therapy. Additional safety information can be found below.
Steglatro is available in 5 mg and 15 mg tablets.
Merck-Pfizer Collaboration and Product Availability
In 2013, Merck and Pfizer announced that they entered into a worldwide collaboration, except Japan, for the co-development and co-promotion of ertugliflozin. The Merck sales force will exclusively promote Steglatro and two fixed-dose combination products in the United States. Merck and Pfizer will share potential revenues and certain costs on a 60/40 percent basis, respectively, and Pfizer may be entitled to additional milestone payments.
Selected Important Risk Information about Steglatro
Ketoacidosis, a serious life-threatening condition requiring urgent hospitalization, has been reported in patients with type 1 and type 2 diabetes receiving SGLT2 inhibitors including Steglatro. Some cases were fatal. Assess patients with signs and symptoms of metabolic acidosis for ketoacidosis, regardless of blood glucose level. If ketoacidosis is suspected, Steglatro should be discontinued, patient should be evaluated, and prompt treatment should be instituted. Before initiating Steglatro, consider risk factors for ketoacidosis, including pancreatic insulin deficiency from any cause, caloric restriction, and alcohol abuse. In patients treated with Steglatro, consider monitoring for ketoacidosis and temporarily discontinuing Steglatro in clinical situations known to predispose to ketoacidosis (e.g., prolonged fasting due to acute illness or surgery).
Steglatro causes intravascular volume contraction and can cause renal impairment. There have been postmarketing reports of acute kidney injury, some requiring hospitalization and dialysis, in patients receiving SGLT2 inhibitors. Before initiating Steglatro, consider factors that may predispose patients to acute kidney injury. Consider temporarily discontinuing Steglatro in any setting of reduced oral intake or fluid losses; monitor patients for signs and symptoms of acute kidney injury. If acute kidney injury occurs, discontinue Steglatro promptly and institute treatment.
Steglatro increases serum creatinine and decreases eGFR. Patients with moderate renal impairment (eGFR 30 to less than 60 mL/min/1.73 m2) may be more susceptible to these changes. Renal function abnormalities can occur after initiating Steglatro. Renal function should be evaluated prior to initiating Steglatro and periodically thereafter. Use of Steglatro is not recommended when eGFR is persistently between 30 and less than 60 mL/min/1.73 m2 and is contraindicated in patients with an eGFR less than 30 mL/min/1.73 m2.
There have been postmarketing reports of serious urinary tract infections, including urosepsis and pyelonephritis, requiring hospitalization in patients receiving SGLT2 inhibitors. Cases of pyelonephritis also have been reported in patients treated with STEGLATRO in clinical trials. Treatment with SGLT2 inhibitors increases the risk for urinary tract infections. Evaluate patients for signs and symptoms of urinary tract infections and treat promptly, if indicated.
An increased risk for lower limb amputation has been observed in clinical studies with another SGLT2 inhibitor. Across seven Phase 3 clinical trials with Steglatro, non-traumatic lower limb amputations were reported in 1 (0.1%) patient in the comparator group, 3 (0.2%) patients in the Steglatro 5 mg group, and 8 (0.5%) patients in the Steglatro 15 mg group. A causal association between Steglatro (ertugliflozin) and lower limb amputation has not been definitively established. Before initiating Steglatro, consider factors that may predispose patients to the need for amputations. Counsel patients about the importance of routine preventative foot care. Monitor patients and discontinue Steglatro if complications occur.
Insulin and insulin secretagogues (e.g., sulfonylurea) are known to cause hypoglycemia. Steglatro may increase the risk of hypoglycemia when used in combination with insulin and/or an insulin secretagogue. Therefore, a lower dose of insulin or insulin secretagogue may be required to minimize the risk of hypoglycemia when used in combination with Steglatro.
Steglatro increases the risk of genital mycotic infections. Patients who have a history of genital mycotic infections or who are uncircumcised are more likely to develop genital mycotic infections. Monitor and treat appropriately.
Dose-related increases in low-density lipoprotein cholesterol (LDL-C) can occur with Steglatro. Monitor and treat as appropriate.
There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with Steglatro.
The most common adverse reactions associated with Steglatro (incidence ≥5%) were female genital mycotic infections.
For more than a century, Merck, a leading global biopharmaceutical company known as MSD outside of the United States and Canada, has been inventing for life, bringing forward medicines and vaccines for many of the world’s most challenging diseases. 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 health care through far-reaching policies, programs and partnerships. Today, Merck continues to be at the forefront of research to advance the prevention and treatment of diseases that threaten people and communities around the world - including cancer, cardio-metabolic diseases, emerging animal diseases, Alzheimer’s disease and infectious diseases including HIV and Ebola. For more information, visit www.merck.com and connect with us on Twitter, Facebook, Instagram, YouTube and LinkedIn.
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This news release of Merck & Co., Inc., Kenilworth, N.J., USA (the “company”) includes “forward-looking statements” within the meaning of the safe harbor provisions of the U.S. 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.
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Pfizer Disclosure Notice
The information contained in this release is current as of December 22, 2017. Pfizer assumes no obligation to update forward-looking statements contained in this release as the result of new information or future events or developments.
This release contains forward-looking information about Steglatro (ertugliflozin) including the potential benefits, that involves substantial risks and uncertainties that could cause actual results to differ materially from those expressed or implied by such statements. Risks and uncertainties include, among other things, uncertainties regarding the commercial success of Steglatro; the uncertainties inherent in research and development, including the ability to meet anticipated clinical trial commencement and completion dates and regulatory submission dates, as well as the possibility of unfavorable clinical trial results, including unfavorable new clinical data and additional analyses of existing clinical data; whether and when applications for Steglatro may be filed in any other jurisdictions; whether and when any such other applications for Steglatro that may be pending or filed may be approved by regulatory authorities, which will depend on the assessment by such regulatory authorities of the benefit-risk profile suggested by the totality of the efficacy and safety information submitted; decisions by regulatory authorities regarding labeling and other matters that could affect the availability or commercial potential of Steglatro and competitive developments. The competitive landscape for type 2 diabetes therapies, including SGLT2 inhibitors, continues to evolve. The success of our ertugliflozin program is dependent on developments in that space.
A further description of risks and uncertainties can be found in Pfizer’s Annual Report on Form 10-K for the fiscal year ended December 31, 2016 and in its subsequent reports on Form 10-Q, including in the sections thereof captioned “Risk Factors” and “Forward-Looking Information and Factors That May Affect Future Results”, as well as in its subsequent reports on Form 8-K, all of which are filed with the U.S. Securities and Exchange Commission and available at www.sec.gov and www.pfizer.com.
Source: Merck & Co., Inc.
Posted: December 2017
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