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FDA Approves Segluromet

FDA Approves Segluromet (ertugliflozin and metformin hydrochloride) 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 Segluromet (ertugliflozin and metformin hydrochloride) tablets. Ertugliflozin is a newly approved oral sodium-glucose cotransporter 2 (SGLT2) inhibitor.

Segluromet is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus who are not adequately controlled on a regimen containing ertugliflozin or metformin, or in patients who are already treated with both ertugliflozin and metformin. Segluromet is not recommended in patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis. The labeling for Segluromet contains a boxed warning for lactic acidosis. Segluromet is contraindicated in patients with severe renal impairment, end-stage renal disease or on dialysis, acute or chronic metabolic acidosis, including diabetic ketoacidosis, or a history of a serious hypersensitivity reaction to Segluromet, ertugliflozin or metformin hydrochloride.

Segluromet combines 2.5 mg or 7.5 mg of ertugliflozin with 500 mg or 1,000 mg of metformin hydrochloride.

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 ertugliflozin and the 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 Segluromet

Postmarketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias. The onset of metformin-associated lactic acidosis is often subtle, accompanied only by nonspecific symptoms such as malaise, myalgias, respiratory distress, somnolence, and abdominal pain. Metformin-associated lactic acidosis was characterized by elevated blood lactate levels (>5 mmol/Liter), anion gap acidosis (without evidence of ketonuria or ketonemia), an increased lactate/pyruvate ratio and metformin plasma levels generally >5 mcg/mL.

Risk factors for metformin-associated lactic acidosis include renal impairment, concomitant use of certain drugs (e.g., carbonic anhydrase inhibitors such as topiramate), age 65 years old or greater, having a radiological study with contrast, surgery and other procedures, hypoxic states (e.g., acute congestive heart failure), excessive alcohol intake, and hepatic impairment.

If metformin-associated lactic acidosis is suspected, immediately discontinue Segluromet (ertugliflozin and metformin hydrochloride) and institute general supportive measures in a hospital setting. Prompt hemodialysis is recommended.

Educate patients and their families about the symptoms of lactic acidosis and, if these symptoms occur, instruct them to discontinue Segluromet and promptly notify their health care provider.

Recommendations to reduce the risk include:

Ertugliflozin causes intravascular volume contraction and symptomatic hypotension may occur after initiating Segluromet, particularly in patients with impaired renal function (eGFR less than 60 mL/min/1.73 m2), elderly patients (≥65 years), or patients on diuretics. Before initiating Segluromet (ertugliflozin and metformin hydrochloride), assess and correct volume status. Monitor for hypotension.

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 ertugliflozin. Some cases were fatal. Assess patients with signs and symptoms of metabolic acidosis for ketoacidosis, regardless of blood glucose level. If ketoacidosis is suspected, Segluromet should be discontinued, patient should be evaluated, and prompt treatment should be instituted. Before initiating Segluromet, consider risk factors for ketoacidosis, including pancreatic insulin deficiency from any cause, caloric restriction, and alcohol abuse. In patients treated with Segluromet, consider monitoring for ketoacidosis and temporarily discontinuing Segluromet in clinical situations known to predispose to ketoacidosis (e.g., prolonged fasting due to acute illness or surgery).

Segluromet causes intravascular volume contraction and can cause renal impairment. There have been reports of acute kidney injury, some requiring hospitalization and dialysis, in patients receiving SGLT2 inhibitors. Before initiating Segluromet, consider factors that may predispose patients to acute kidney injury. Consider temporarily discontinuing Segluromet 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 Segluromet promptly and institute treatment.

Segluromet 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 Segluromet. Renal function should be evaluated prior to initiating Segluromet and periodically thereafter. Use of Segluromet 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 ertugliflozin-treated patients in clinical trials. Treatment with SGLT2 inhibitors increases the risk for urinary tract infections. Evaluate for urinary tract infections and treat promptly.

An increased risk for lower limb amputation has been observed in clinical studies with another SGLT2 inhibitor. Across seven Phase 3 clinical trials with ertugliflozin, non-traumatic lower limb amputations were reported in 1 (0.1%) patient in the comparator group, 3 (0.2%) patients in the ertugliflozin 5 mg group, and 8 (0.5%) patients in the ertugliflozin 15 mg group. A causal association between ertugliflozin and lower limb amputation has not been definitively established. Before initiating Segluromet, 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 Segluromet (ertugliflozin and metformin hydrochloride) if complications occur.

Ertugliflozin may increase the risk of hypoglycemia when combined with insulin and/or an insulin secretagogue. Consider lowering the dose of these agents when coadministered with Segluromet. Hypoglycemia could occur when caloric intake is deficient, when strenuous exercise is not compensated by caloric supplementation or during concomitant use of other glucose-lowering agents or with the use of ethanol.

Ertugliflozin increases the risk of genital mycotic infections, particularly in patients with a history of these infections or who are uncircumcised. Monitor and treat appropriately.

Dose-related increases in LDL-C can occur with Segluromet. Monitor and treat as appropriate.

There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with Segluromet.

The most common adverse reactions associated with ertugliflozin (incidence ≥5%) were female genital mycotic infections. The most common adverse reactions associated with metformin (incidence ≥5%) were diarrhea, nausea, vomiting, flatulence, abdominal discomfort, indigestion, asthenia and headache.

About Merck

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.

About Pfizer Inc.: Working together for a healthier world ®

At Pfizer, we apply science and our global resources to bring therapies to people that extend and significantly improve their lives. We strive to set the standard for quality, safety and value in the discovery, development and manufacture of health care products. Our global portfolio includes medicines and vaccines as well as many of the world’s best-known consumer health care products. Every day, Pfizer colleagues work across developed and emerging markets to advance wellness, prevention, treatments and cures that challenge the most feared diseases of our time. Consistent with our responsibility as one of the world’s premier innovative biopharmaceutical companies, we collaborate with health care providers, governments and local communities to support and expand access to reliable, affordable health care around the world. For more than 150 years, we have worked to make a difference for all who rely on us. We routinely post information that may be important to investors on our website at www.pfizer.com. In addition, to learn more, please visit us on www.pfizer.com and follow us on Twitter at @Pfizer and @Pfizer_News, LinkedIn, YouTube and like us on Facebook at Facebook.com/Pfizer.

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

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.

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 health care legislation in the United States and internationally; global trends toward health care 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 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 2016 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).

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), STEGLUJAN (ertugliflozin and sitagliptin) and SEGLUROMET (ertugliflozin and metformin hydrochloride), including their 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, STEGLUJAN and SEGLUROMET; 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, STEGLUJAN, and SEGLUROMET may be filed in any other jurisdictions; whether and when any such other applications for STEGLATRO, STEGLUJAN and SEGLUROMET 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, STEGLUJAN, and SEGLUROMET; 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

Posted: December 2017

Segluromet (ertugliflozin and metformin hydrochloride) FDA Approval History

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