FDA approves Ozempic® for cardiovascular risk reduction in adults with type 2 diabetes and known heart disease, updates Rybelsus® label

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Jan 16, 2020, 17:56 ET

PLAINSBORO, N.J., Jan. 16, 2020 /PRNewswire/ -- Novo Nordisk today announced that the U.S. Food and Drug Administration (FDA) has approved a new indication for Ozempic^® (semaglutide) injection 0.5 mg or 1 mg to reduce the risk of major adverse cardiovascular events (MACE) such as heart attack, stroke, or death in adults with type 2 diabetes and known heart disease.¹ Additional details were added to the Rybelsus^® (semaglutide) tablets 7 mg or 14 mg Prescribing Information about the primary analysis for PIONEER 6.

Cardiovascular disease (CVD) is the main cause of death and disability among people with type 2 diabetes.² Adults with type 2 diabetes are two to four times more likely to develop CVD than adults without diabetes.³

The FDA's decision on Ozempic^® is based on results from the SUSTAIN 6 cardiovascular outcomes trial (CVOT) which examined the cardiovascular safety of adding Ozempic^® or placebo to standard of care in adults with type 2 diabetes and established cardiovascular disease. In the 2-year SUSTAIN 6 trial, Ozempic^® significantly reduced the risk of the occurrence of a three-component MACE endpoint consisting of cardiovascular death, non-fatal heart attack or non-fatal stroke. The estimated relative risk reduction of MACE was 26% vs placebo (HR 0.74 [95% CI: 0.58, 0.95], p<0.001 for noninferiority, median observation time 2.1 years) with the primary composite outcome occurring in 6.6% of patients treated with Ozempic^® vs 8.9% with placebo.^1,4 During the trial, gastrointestinal adverse events were more frequent in the Ozempic^® group than in the placebo group. The majority of gastrointestinal adverse events occurred during the first 30 weeks.⁴

"There is a well-established link between cardiovascular disease and type 2 diabetes. It's one of our biggest concerns with type 2 diabetes because even when patients reach their blood sugar targets, the risk of a major adverse CV event remains," said Todd Hobbs, vice president and U.S. chief medical officer of Novo Nordisk. "Today's milestone establishes Ozempic^® as an option for patients to help address two critical aspects of managing type 2 diabetes, blood sugar control and cardiovascular risk reduction, in those with known heart disease."

The Rybelsus^® prescribing information has been updated in section 14 (clinical studies) to include an analysis from the primary endpoint of the PIONEER 6 CVOT showing the hazard ratio for time to first three-component MACE (HR 0.79 [95% CI: 0.57, 1.11]).⁵

In June 2019, Novo Nordisk initiated the SOUL CVOT in 9,642 adults with type 2 diabetes and established cardiovascular disease to further evaluate the cardiovascular effect of Rybelsus^®. The trial is investigating the effects of Rybelsus^®on the incidence of MACE vs placebo in addition to standard of care.

About the SUSTAIN 6 Trial
SUSTAIN 6 was an event- and time-driven, pre-approval CVOT for Ozempic^®. It was a randomized, double-blinded, noninferiority placebo-controlled trial evaluating the cardiovascular safety of Ozempic^® vs placebo when added to standard of care in 3,297 adults with type 2 diabetes with established CVD for a minimum observation period of two years.

About Ozempic^®Ozempic^® (semaglutide) injection 0.5 mg or 1 mg is a once-weekly glucagon-like peptide-1 (GLP-1) receptor agonist indicated along with diet and exercise to improve blood sugar (glucose) in adults with type 2 diabetes mellitus and to reduce the risk of major cardiovascular events such as heart attack, stroke or death in adults with type 2 diabetes mellitus with known heart disease. Ozempic^® was approved by the U.S. Food and Drug Administration on December 5, 2017, by Health Canada on January 4, 2018, by the European Commission on February 9, 2018, by the Japanese Ministry of Health, Labour and Welfare on March 23, 2018, by Swissmedic on July 2, 2018, and by the Brazilian National Health Surveillance Agency on August 6, 2018.

What is Ozempic^®?
Ozempic^® (semaglutide) injection 0.5 mg or 1 mg is an injectable prescription medicine used:

along with diet and exercise to improve blood sugar (glucose) in adults with type 2 diabetes mellitus.
to reduce the risk of major cardiovascular events such as heart attack, stroke or death in adults with type 2 diabetes mellitus with known heart disease.

It is not known if Ozempic^® can be used in people who have had pancreatitis.
Ozempic^® is not a substitute for insulin and is not for use in people with type 1 diabetes or people with diabetic ketoacidosis.
It is not known if Ozempic^® is safe and effective for use in children under 18 years of age.

Important Safety Information

Do not share your Ozempic^® pen with other people, even if the needle has been changed. You may give other people a serious infection, or get a serious infection from them.

What is the most important information I should know about Ozempic^®?
Ozempic^® may cause serious side effects, including:

Possible thyroid tumors, including cancer. Tell your health care provider if you get a lump or swelling in your neck, hoarseness, trouble swallowing, or shortness of breath. These may be symptoms of thyroid cancer. In studies with rodents, Ozempic^® and medicines that work like Ozempic^®caused thyroid tumors, including thyroid cancer. It is not known if Ozempic^® will cause thyroid tumors or a type of thyroid cancer called medullary thyroid carcinoma (MTC) in people.
Do not use Ozempic^® if you or any of your family have ever had MTC, or if you have an endocrine system condition called Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).

Do not use Ozempic^® if:

you or any of your family have ever had MTC or if you have MEN 2.
you are allergic to semaglutide or any of the ingredients in Ozempic^®.

Before using Ozempic^®, tell your health care provider if you have any other medical conditions, including if you:

have or have had problems with your pancreas or kidneys.
have a history of diabetic retinopathy.
are pregnant or breastfeeding or plan to become pregnant or breastfeed. It is not known if Ozempic^® will harm your unborn baby or passes into your breast milk. You should stop using Ozempic^® 2 months before you plan to become pregnant.

Tell your health care provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, herbal supplements, and other medicines to treat diabetes, including insulin or sulfonylureas.

What are the possible side effects of Ozempic^®?
Ozempic^® may cause serious side effects, including:

inflammation of your pancreas (pancreatitis). Stop using Ozempic^® and call your health care provider right away if you have severe pain in your stomach area (abdomen) that will not go away, with or without vomiting. You may feel the pain from your abdomen to your back.
changes in vision. Tell your health care provider if you have changes in vision during treatment with Ozempic^®.
low blood sugar (hypoglycemia). Your risk for getting low blood sugar may be higher if you use Ozempic^®with another medicine that can cause low blood sugar, such as a sulfonylurea or insulin. Signs and symptoms of low blood sugar may include: dizziness or lightheadedness, blurred vision, anxiety, irritability or mood changes, sweating, slurred speech, hunger, confusion or drowsiness, shakiness, weakness, headache, fast heartbeat, and feeling jittery.
kidney problems (kidney failure). In people who have kidney problems, diarrhea, nausea, and vomiting may cause a loss of fluids (dehydration), which may cause kidney problems to get worse. It is important for you to drink fluids to help reduce your chance of dehydration.
serious allergic reactions. Stop using Ozempic^® and get medical help right away if you have any symptoms of a serious allergic reaction, including itching, rash, or difficulty breathing.

The most common side effects of Ozempic^® may include nausea, vomiting, diarrhea, stomach (abdominal) pain, and constipation.

Please see Medication Guide and Prescribing Information, including Boxed Warning, for Ozempic^® at http://www.novo-pi.com/ozempic.pdf.

About Rybelsus^®Rybelsus^® (semaglutide) tablets 7 mg or 14 mg is an analog of the naturally occurring hormone glucagon-like peptide-1 (GLP-1).⁵ Rybelsus^® is the first and only GLP-1 receptor agonist (RA) in a pill. It is taken once daily and is approved for use in two therapeutic doses: 7 mg and 14 mg.

What is Rybelsus^®?
Rybelsus^® (semaglutide) tablets 7 mg or 14 mg is a prescription medicine for adults with type 2 diabetes that along with diet and exercise may improve blood sugar (glucose).

Rybelsus^® is not recommended as the first choice of medicine for treating diabetes
It is not known if Rybelsus^® can be used in people who have had pancreatitis
Rybelsus^® is not for use in people with type 1 diabetes and people with diabetic ketoacidosis
It is not known if Rybelsus^® is safe and effective for use in children under 18 years of age

Important Safety Information

What is the most important information I should know about Rybelsus^®?
Rybelsus^® may cause serious side effects, including:

Possible thyroid tumors, including cancer. Tell your healthcare provider if you get a lump or swelling in your neck, hoarseness, trouble swallowing, or shortness of breath. These may be symptoms of thyroid cancer. In studies with rodents, Rybelsus^® and medicines that work like Rybelsus^® caused thyroid tumors, including thyroid cancer. It is not known if Rybelsus^® will cause thyroid tumors or a type of thyroid cancer called medullary thyroid carcinoma (MTC) in people

Do not use Rybelsus^® if:

you or any of your family have ever had MTC, or if you have an endocrine system condition called Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)
you are allergic to semaglutide or any of the ingredients in Rybelsus^®

Before using Rybelsus^®, tell your healthcare provider if you have any other medical conditions, including if you:

have or have had problems with your pancreas or kidneys
have a history of vision problems related to your diabetes
are pregnant or plan to become pregnant. It is not known if Rybelsus^® will harm your unborn baby. You should stop using Rybelsus^® 2 months before you plan to become pregnant. Talk to your healthcare provider about the best way to control your blood sugar if you plan to become pregnant or while you are pregnant
are breastfeeding or plan to breastfeed. Breastfeeding is not recommended during treatment with Rybelsus^®

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Rybelsus^® may affect the way some medicines work and some medicines may affect the way Rybelsus^® works.

How should I take Rybelsus^®?

Take Rybelsus^® exactly as your healthcare provider tells you to
Take Rybelsus^® by mouth on an empty stomach when you first wake up with a sip of plain water (no more than 4 ounces)
Do not split, crush, or chew. Swallow Rybelsus^® whole
After 30 minutes, you can eat, drink, or take other oral medications. Rybelsus^® works best if you eat 30 to 60 minutes after taking it
If you miss a dose of Rybelsus^®, skip the missed dose and go back to your regular schedule

What are the possible side effects of Rybelsus^®?
Rybelsus^® may cause serious side effects, including:

inflammation of your pancreas (pancreatitis). Stop using Rybelsus^® and call your healthcare provider right away if you have severe pain in your stomach area (abdomen) that will not go away, with or without vomiting. You may feel the pain from your abdomen to your back
changes in vision. Tell your healthcare provider if you have changes in vision during treatment with Rybelsus^®
low blood sugar (hypoglycemia). Your risk for getting low blood sugar may be higher if you use Rybelsus^® with another medicine that can cause low blood sugar, such as a sulfonylurea or insulin. Signs and symptoms of low blood sugar may include: dizziness or lightheadedness, blurred vision, anxiety, irritability or mood changes, sweating, slurred speech, hunger, confusion or drowsiness, shakiness, weakness, headache, fast heartbeat, and feeling jittery
kidney problems (kidney failure). In people who have kidney problems, diarrhea, nausea, and vomiting may cause a loss of fluids (dehydration), which may cause kidney problems to get worse. It is important for you to drink fluids to help reduce your chance of dehydration
serious allergic reactions. Stop using Rybelsus^® and get medical help right away, if you have any symptoms of a serious allergic reaction including itching, rash, or difficulty breathing

The most common side effects of Rybelsus^® may include nausea, stomach (abdominal) pain, diarrhea, decreased appetite, vomiting, and constipation. Nausea, vomiting, and diarrhea are most common when you first start Rybelsus^®.

Please see Medication Guide and Prescribing Information, including Boxed Warning, for Rybelsus^® at https://www.novo-pi.com/rybelsus.pdf.

About Novo Nordisk
Novo Nordisk is a global healthcare company that's been making innovative medicines to help people with diabetes lead longer, healthier lives for 95 years. This heritage has given us experience and capabilities that also enable us to help people defeat other serious diseases including obesity, hemophilia and growth disorders. We remain steadfast in our conviction that the formula for lasting success is to stay focused, think long-term and do business in a financially, socially and environmentally responsible way. With U.S. headquarters in New Jersey and production and research facilities in six states, Novo Nordisk employs nearly 6,000 people throughout the country. For more information, visit novonordisk.us, Facebook, Instagram and Twitter.

References

Ozempic^® [package insert]. Plainsboro, NJ: Novo Nordisk Inc; January 2020.
Low Wang CC, Hess CN, Hiatt WR, Goldfine AB. Clinical Update: Cardiovascular disease in diabetes mellitus: Atherosclerotic cardiovascular disease and heart failure in type 2 diabetes mellitus - mechanisms, Management, and Clinical Considerations. Circulation. 2016;133(24):2459-2502.
World Heart Federation. Cardiovascular disease risk factors. Available at: www.world-heart-federation.org/cardiovascular-health/cardiovascular-disease-risk-factors/diabetes/. Accessed January 9, 2020.
Marso SP, Bain SC, Consoli A, et al; SUSTAIN-6 Investigators. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. 2016:375:1834-1844.
Rybelsus^® [package insert]. Plainsboro, NJ: Novo Nordisk Inc; January 2020.