`
`
`
`
`
` ∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙DOSAGE FORMS AND STRENGTHS∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙
`
`
`
`
`
` Injection: pre-filled, single-dose pen that delivers doses of 0.25 mg, 0.5 mg, 1
`
`
`
` mg, 1.7 mg or 2.4 mg (3).
`
`
`
`
`
`∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙CONTRAINDICATIONS∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙
`
`
`
`
`
`
`
`Personal or family history of MTC or in patients with MEN2 (4).
`•
`
`
`
`
`
`Known hypersensitivity to semaglutide or any of the excipients in
`•
`
`
`WEGOVY (4).
`
`
`
`∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙WARNINGS AND PRECAUTIONS∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙
`
`
`
`
`
`Acute Pancreatitis: Has occurred in clinical trials. Discontinue promptly if
`•
`
`
`
`
`
`
`pancreatitis is suspected. Do not restart if pancreatitis is confirmed (5.2).
`
`
`
`
`Acute Gallbladder Disease: Has occurred in clinical trials. If cholelithiasis
`
`
`
`is suspected, gallbladder studies and clinical follow-up are indicated (5.3).
`
`
`
`
`
`
`
`Hypoglycemia: Concomitant use with insulin or an insulin secretagogue
`
`
`
`may increase the risk of hypoglycemia, including severe hypoglycemia.
`
`
`
`
`
`
`
`
`Reducing the dose of insulin or insulin secretagogue may be necessary.
`
`
`
`
`
`Inform all patients of the risk of hypoglycemia and educate them on the
`
`
`
`
`signs and symptoms of hypoglycemia (5.4).
`
`
`
`
`Acute Kidney Injury: Has occurred. Monitor renal function when initiating
`
`
`
`or escalating doses of WEGOVY in patients reporting severe adverse
`
`
`
`
`gastrointestinal reactions or in those with renal impairment reporting severe
`
`
`adverse gastrointestinal reactions (5.5).
`
`
`
`
`Hypersensitivity Reactions: Anaphylactic reactions and angioedema have
`
`
`
`
`
`
`been reported postmarketing. Discontinue WEGOVY if suspected and
`
`promptly seek medical advice (5.6).
`
`Diabetic Retinopathy Complications in Patients with Type 2 Diabetes: Has
`
`
`
`
`
`
`
`
`been reported in trials with semaglutide. Patients with a history of diabetic
`
`
`retinopathy should be monitored (5.7).
`
`
`
`Heart Rate Increase: Monitor heart rate at regular intervals (5.8).
`
`
`
`
`Suicidal Behavior and Ideation: Monitor for depression or suicidal
`
`
`
`
`thoughts. Discontinue WEGOVY if symptoms develop (5.9).
`
`
`•
`
`
`•
`
`
`•
`
`
`•
`
`
`•
`
`
`•
`
`•
`
`
`
`∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙ADVERSE REACTIONS∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙
`
`
`
`
`Most common adverse reactions (incidence ≥ 5%) in adults or pediatric patients
`
`
`
`
`
`aged 12 years and older are: nausea, diarrhea, vomiting, constipation, abdominal
`
`
`pain, headache, fatigue, dyspepsia, dizziness, abdominal distension, eructation,
`
`
`
`
`hypoglycemia in patients with type 2 diabetes, flatulence, gastroenteritis,
`
`
`
`
`gastroesophageal reflux disease, and nasopharyngitis (6.1).
`
`
`To report SUSPECTED ADVERSE REACTIONS, contact Novo Nordisk
`
`
`
`Inc., at 1-833-934-6891 or FDA at 1-800-FDA-1088 or
`
`www.fda.gov/medwatch.
`
`------------------------------DRUG INTERACTIONS-----------------------------------
`
`
`
`
`
`
`WEGOVY delays gastric emptying. May impact absorption of concomitantly
`
`
`administered oral medications. Use with caution (7.2).
`
`
`∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙USE IN SPECIFIC POPULATIONS∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙
`
`
`
`
`
`
`Pregnancy: May cause fetal harm. When pregnancy is recognized,
`•
`
`
`
`discontinue WEGOVY (8.1).
`
`
`
`
`Females and Males of Reproductive Potential: Discontinue WEGOVY at
`
`
`
`
`
`
`
`least 2 months before a planned pregnancy because of the long half-life of
`
`semaglutide (8.3).
`
`
`•
`
`
`
`
`
`See 17 for PATIENT COUNSELING INFORMATION and
`
`Medication Guide.
`
`
`
`
`Revised: 03/2024
`
`
` HIGHLIGHTS OF PRESCRIBING INFORMATION
` These highlights do not include all the information needed to use
`
`
`
`
`
` WEGOVY safely and effectively. See full prescribing information for
` WEGOVY.
`
`
`WEGOVY (semaglutide) injection, for subcutaneous use
`
`
`Initial U.S. Approval: 2017
`
`
`
`
`
`
`
` WARNING: RISK OF THYROID C-CELL TUMORS
`
`
`
`
`
`
` See full prescribing information for complete boxed warning.
`
` • In rodents, semaglutide causes thyroid C-cell tumors at clinically
`
`
`
`
`
`
` relevant exposures. It is unknown whether WEGOVY causes
` thyroid C-cell tumors, including medullary thyroid carcinoma
`
`
`
` (MTC), in humans as the human relevance of semaglutide-induced
` rodent thyroid C-cell tumors has not been determined (5.1, 13.1).
`
`• WEGOVY is contraindicated in patients with a personal or
`
`
`
`
`family history of MTC or in patients with Multiple Endocrine
`
`
`
`
`Neoplasia syndrome type 2 (MEN 2). Counsel patients regarding
`
`
`
`
` the potential risk of MTC and symptoms of thyroid tumors (4, 5.1).
`
`
`
`
`
`
`
` ∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙RECENT MAJOR CHANGES∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙
`
`
`
` 03/2024
` Indications and Usage (1)
` Dosing and Administration (2.2)
`
`
` 07/2023
` Warnings and Precaution, Hypoglycemia (5.4) 03/2024
`
`
`
`
`
` ∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙INDICATIONS AND USAGE∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙
`WEGOVY is a glucagon-like peptide-1 (GLP-1) receptor agonist
`
`
`
`
`indicated in combination with a reduced calorie diet and increased
`
`
`
`
`
`
`physical activity:
`
`to reduce the risk of major adverse cardiovascular events
`
`
`
`
`•
`(cardiovascular death, non-fatal myocardial infarction, or non-fatal
`
`
`stroke) in adults with established cardiovascular disease and either
`
`
`
`
`
`obesity or overweight (1).
`
`
`to reduce excess body weight and maintain weight reduction long
`
`
`
`
`term in:
`
`
`o Adults and pediatric patients aged 12 years and older
`
`
`
`
`with obesity
`
`o Adults with overweight in the presence of at least one
`
`
`
`
`
`
`weight-related comorbid condition (1).
`
`
`
`Limitations of Use:
`
`
`• Coadministration with other semaglutide-containing products or
`
`
`
`with any other GLP-1 receptor agonist is not recommended (1).
`
`
`
`
`
`
`
`
`•
`
`
`∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙DOSAGE AND ADMINISTRATION∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙
`
`• Administer WEGOVY once weekly as an adjunct to diet and
`
`
`
`
`increased physical activity, on the same day each week, at any time
`
`
`of day, with or without meals (2.1).
`
`
`
`
`Inject subcutaneously in the abdomen, thigh or upper arm (2.1).
`
`
`
`
`
`
`•
`• In patients with type 2 diabetes, monitor blood glucose prior to
`
`
`
`
`
`starting and during WEGOVY treatment (2.1).
`
`
`
`• Initiate at 0.25 mg once weekly for 4 weeks. Then follow the dosage
`
`
`
`escalation schedule, titrating every 4 weeks to achieve the
`
`
`
`maintenance dosage (2.2, 2.3).
`
`
`• The maintenance dosage of WEGOVY in adults is either 2.4 mg
`
`
`
`
`
`
`
`(recommended) or 1.7 mg once weekly (2.2).
`
`
`
`
`• The maintenance dosage of WEGOVY in pediatric patients aged 12
`
`
`
`
`
`years and older is 2.4 mg once weekly (2.3).
`
`
`
`
`
`
`
`
`Reference ID: 5342984
`
`MPI EXHIBIT 1106 PAGE 1
`
`

`

`
`
`
`
`
`
`
`
`8
`
`
`USE IN SPECIFIC POPULATIONS
`
`
`8.1 Pregnancy
`
`
`8.2 Lactation
`
`
`
`
`8.3 Females and Males of Reproductive Potential
`
`
`8.4 Pediatric Use
`
`
`8.5 Geriatric Use
`
`
`8.6 Renal Impairment
`
`
`
`8.7 Hepatic Impairment
`
`
`10
`OVERDOSAGE
`
`
`11
`DESCRIPTION
`
`
`12
`CLINICAL PHARMACOLOGY
`
`
`12.1 Mechanism of Action
`
`12.2 Pharmacodynamics
`
`12.3 Pharmacokinetics
`
`12.6 Immunogenicity
`NONCLINICAL TOXICOLOGY
`
`
`13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
`
`
`CLINICAL STUDIES
`
`
`
`
`14.1 Cardiovascular Outcomes Trial in Adult Patients with
`
`
`
`
`Cardiovascular Disease and Either Obesity or Overweight
`
`
`
`
`14.2 Weight Reduction and Long-term Maintenance Studies in
`
`
`
`Adults with Obesity or Overweight
`
`
`
`
`14.3 Weight Reduction and Long-Term Maintenance Study in
`
`
`Pediatric Patients Aged 12 Years and Older with Obesity
`
`
`HOW SUPPLIED/STORAGE AND HANDLING
`16
`
`
`17
` PATIENT COUNSELING INFORMATION
`
`*Sections or subsections omitted from the full prescribing information are not
`
`
`
`
`
`
`listed.
`
`
`13
`
`14
`
` INDICATIONS AND USAGE
`
` DOSAGE AND ADMINISTRATION
`
`
`
`
` 2.1 Important Monitoring and Administration Instructions
`
` 2.2 Recommended Dosage in Adults
`
`
`
` 2.3 Recommended Dosage in Pediatric Patients Aged 12
`
`
` Years and Older
`
` 2.4 Recommendations Regarding Missed Dose
`
`
`
` DOSAGE FORMS AND STRENGTHS
`
` CONTRAINDICATIONS
` WARNINGS AND PRECAUTIONS
`
`
`
` 5.1 Risk of Thyroid C-Cell Tumors
`
` 5.2 Acute Pancreatitis
`
`
` 5.3 Acute Gallbladder Disease
`
`
` 5.4 Hypoglycemia
`
`
`
` 5.5 Acute Kidney Injury
`
`
`
` 5.6 Hypersensitivity Reactions
`
`
` 5.7 Diabetic Retinopathy Complications in Patients with
`
`
`
` Type 2 Diabetes
`
`
` 5.8 Heart Rate Increase
`
`
` 5.9 Suicidal Behavior and Ideation
`
`
` ADVERSE REACTIONS
`
` 6.1 Clinical Trials Experience
`
`
`
` 6.2 Postmarketing Experience
` DRUG INTERACTIONS
`
`
` 7.1 Concomitant Use with Insulin or an Insulin Secretagogue
`
`
`
` (e.g., Sulfonylurea)
` 7.2 Oral Medications
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` FULL PRESCRIBING INFORMATION: CONTENTS*
`
`
`
` WARNING: RISK OF THYROID C-CELL TUMORS
`
`
` 1
`
` 2
`
`
`
`
`
`
`
`
` 3
`
` 4
`
` 5
`
`
`
` 6
`
`
`
` 7
`
`Reference ID: 5342984
`
`MPI EXHIBIT 1106 PAGE 2
`
`

`

`
`
` FULL PRESCRIBING INFORMATION
`
`
`•
`
` WARNING: RISK OF THYROID C-CELL TUMORS
`
`In rodents, semaglutide causes dose-dependent and treatment-duration-dependent thyroid
`
`
` C-cell tumors at clinically relevant exposures. It is unknown whether WEGOVY causes
`thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans as human
`relevance of semaglutide-induced rodent thyroid C-cell tumors has not been determined [see
`
`Warnings and Precautions (5.1) and Nonclinical Toxicology (13.1)].
`
`
`
`
`• WEGOVY is contraindicated in patients with a personal or family history of MTC or in
`
`
`patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2) [see Contraindications
`
`
`
`(4)]. Counsel patients regarding the potential risk for MTC with the use of WEGOVY and
`inform them of symptoms of thyroid tumors (e.g. a mass in the neck, dysphagia, dyspnea,
`
` persistent hoarseness). Routine monitoring of serum calcitonin or using thyroid ultrasound is
` of uncertain value for early detection of MTC in patients treated with WEGOVY [see
`
`
`
` Contraindications (4) and Warnings and Precautions (5.1)].
`
`
`
`
`
`
`INDICATIONS AND USAGE
`1
`
`
`WEGOVY is indicated in combination with a reduced calorie diet and increased physical activity:
`
`
`
`•
`
`
`•
`
`
`
`
`to reduce the risk of major adverse cardiovascular events (cardiovascular death, non-fatal myocardial
`
`
`infarction, or non-fatal stroke) in adults with established cardiovascular disease and either obesity or
`
`overweight.
`
`
`
`
`to reduce excess body weight and maintain weight reduction long term in:
`
`o Adults and pediatric patients aged 12 years and older with obesity
`
`
`
`
`o Adults with overweight in the presence of at least one weight-related comorbid condition.
`
`
`
`Limitations of Use
`
`
`
`
`
`
`
`• WEGOVY contains semaglutide. Coadministration with other semaglutide-containing products or with
`any other GLP-1 receptor agonist is not recommended.
`
`
`
`2
`
`2.1
`
`•
`
`
`•
`
`
`•
`
`
`DOSAGE AND ADMINISTRATION
`
`
`Important Monitoring and Administration Instructions
`In patients with type 2 diabetes, monitor blood glucose prior to starting WEGOVY and during
`
`
`WEGOVY treatment [see Warnings and Precautions (5.4)].
`
`
`
`• Prior to initiation of WEGOVY, train patients on proper injection technique. Refer to the accompanying
`
`
`Instructions for Use for complete administration instructions with illustrations.
`
`
`Inspect WEGOVY visually prior to each injection. Only use if solution is clear, colorless, and contains
`
`no particles.
`
`
`
`
`
`• Administer WEGOVY in combination with a reduced-calorie diet and increased physical activity.
`
`
`
`
`
`• Administer WEGOVY once weekly, on the same day each week, at any time of day, with or without
`
`meals.
`Inject WEGOVY subcutaneously in the abdomen, thigh, or upper arm. The time of day and the injection
`site can be changed without dose adjustment.
`
`
`
`
`Recommended Dosage in Adults
`2.2
`
`
`Dosage Initiation and Escalation
`
`
`
`
`
`
`
`Initiate WEGOVY with a dosage of 0.25 mg injected subcutaneously once weekly. Then follow the dose
`•
`
`
`escalation schedule presented in Table 1 to minimize gastrointestinal adverse reactions [see Adverse
`Reactions (6.1)].
`
`
`Reference ID: 5342984
`
`MPI EXHIBIT 1106 PAGE 3
`
`

`

`
`•
`
`
`
`
`
`
`
`
`
` If patients do not tolerate a dose during dosage escalation, consider delaying dosage escalation for 4
`
` weeks.
`
`
`Table 1. Recommended Dosage Regimen for Adults
` Once weekly
`
`
` Treatment
` Weeks
`
` Subcutaneous
`
`
` Dosage
`
` 0.25 mg
`
` 0.5 mg
`
`
` 1 mg
`1.7 mg
`
`1.7 mg or 2.4 mg
`
`
`
`
`Initiation
`
` Escalation
`
`
`
`Maintenance
`
`
`1 through 4
`
`5 through 8
`
`9 through 12
`13 through 16
`
` 17 and onward
`
`
`
`
` Maintenance Dosage
`
`
` • The maintenance dosage of WEGOVY in adults is either 2.4 mg (recommended) or 1.7 mg once
`
`
` weekly. Consider treatment response and tolerability when selecting the maintenance dosage [see
`Clinical Studies (14.2)].
`
`
` Recommended Dosage in Pediatric Patients Aged 12 Years and Older
`
` 2.3
`
`
`
`
` Dosage Initiation and Escalation
` Initiate WEGOVY according to the dosage escalation schedule in Table 2 to minimize gastrointestinal
`
`
`
`•
`
` adverse reactions [see Adverse Reactions (6.1)].
`
` If patients do not tolerate a dose during dosage escalation, consider delaying dosage escalation for 4
`
`
` weeks.
` • The 0.25 mg. 0.5 mg, and 1 mg once-weekly dosages are initiation and escalation dosages and are not
`
`approved as maintenance dosages.
`
` Table 2. Recommended Dosage Regimen for Pediatric Patients Aged 12 Years and Older
`
`
`
` Treatment
` Weeks
` Once weekly
` Subcutaneous
`
`
` Dosage
` 0.25 mga
`
`
`0.5 mga
`
`1 mga
`1.7 mgb
`
`
`•
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Initiation
`
`
`
`
`
` Escalation
`
` 1 through 4
`
`
`5 through 8
`
`9 through 12
` 13 through 16
`
`
`
`
`
`Maintenance
`
`
`
` 17 and onward
`
`
`2.4 mg
`
` aNot approved as maintenance dosages
`
`
`
`bSee Dosage Modifications for Adverse Reactions
`
`
` Maintenance Dosage
`
`
` • The maintenance dosage of WEGOVY in pediatric patients aged 12 years and older is 2.4 mg once
`
`weekly.
`
`
`
`
`
`
`
`
` Dosage Modifications for Adverse Reactions
`
`
` If patients do not tolerate the 2.4 mg once-weekly maintenance dosage, the maintenance dosage may be
`•
`
`
` reduced to 1.7 mg once weekly.
` • Discontinue WEGOVY if the patient cannot tolerate the 1.7 mg once-weekly dosage.
`
`
`
`
`
`
`
`
`
`
`
`Reference ID: 5342984
`
`MPI EXHIBIT 1106 PAGE 4
`
`

`

`2.4
`
`
`•
`
`
`•
`
` Recommendations Regarding Missed Dose
`
` If one dose is missed and the next scheduled dose is more than 2 days away (48 hours), administer
`
`
`
` WEGOVY as soon as possible. If one dose is missed and the next scheduled dose is less than 2 days
` away (48 hours), do not administer the dose. Resume dosing on the regularly scheduled day of the week.
` If 2 or more consecutive doses are missed, resume dosing as scheduled or, if needed, reinitiate
`
`
` WEGOVY and follow the dose escalation schedule, which may reduce the occurrence of gastrointestinal
`
`
`
` symptoms associated with reinitiation of treatment.
`
`
`
`
`
`
`
`
`
`DOSAGE FORMS AND STRENGTHS
`3
`
`Injection: clear, colorless solution available in 5 pre-filled, disposable, single-dose pens:
`
`
`• 0.25 mg/0.5 mL
`
`
`• 0.5 mg/0.5 mL
`
`
`• 1 mg/0.5 mL
`
`
`• 1.7 mg/0.75 mL
`
`
`• 2.4 mg/0.75 mL
`
`
`
`
`CONTRAINDICATIONS
`4
`
`WEGOVY is contraindicated in the following conditions:
`
`
`• A personal or family history of MTC or in patients with MEN 2 [see Warnings and Precautions (5.1)].
`
`
`
`
`• A prior serious hypersensitivity reaction to semaglutide or to any of the excipients in WEGOVY.
`Serious hypersensitivity reactions, including anaphylaxis and angioedema, have been reported with
`
`
`WEGOVY [see Warnings and Precautions (5.6)].
`
`
`
`
`5
`WARNINGS AND PRECAUTIONS
`
`5.1
`Risk of Thyroid C-Cell Tumors
`In mice and rats, semaglutide caused a dose-dependent and treatment-duration-dependent increase in the
`
`
`incidence of thyroid C-cell tumors (adenomas and carcinomas) after lifetime exposure at clinically relevant
`
`
`
`plasma exposures [see Nonclinical Toxicology (13.1)]. It is unknown whether WEGOVY causes thyroid C-cell
`
`tumors, including MTC, in humans, as human relevance of semaglutide-induced rodent thyroid C-cell tumors
`
`has not been determined.
`
`
`
`Cases of MTC in patients treated with liraglutide, another GLP-1 receptor agonist, have been reported in the
`
`
`postmarketing period; the data in these reports are insufficient to establish or exclude a causal relationship
`
`between MTC and GLP-1 receptor agonist use in humans.
`
`
`WEGOVY is contraindicated in patients with a personal or family history of MTC or in patients with MEN 2.
`
`
`Counsel patients regarding the potential risk for MTC with the use of WEGOVY and inform them of symptoms
`
`
`of thyroid tumors (e.g. a mass in the neck, dysphagia, dyspnea, persistent hoarseness).
`
`
`
`Routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for early detection of
`
`
`
`MTC in patients treated with WEGOVY. Such monitoring may increase the risk of unnecessary procedures, due
`to the low test specificity for serum calcitonin and a high background incidence of thyroid disease. Significantly
`
`elevated serum calcitonin value may indicate MTC and patients with MTC usually have calcitonin values
`
`
`greater than 50 ng/L. If serum calcitonin is measured and found to be elevated, the patient should be further
`
`
`evaluated. Patients with thyroid nodules noted on physical examination or neck imaging should also be further
`
`evaluated.
`
`
`5.2
`Acute Pancreatitis
`
`Acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, has been observed in
`
`
`patients treated with GLP-1 receptor agonists, including semaglutide. Acute pancreatitis was observed in
`
`
`
`patients treated with WEGOVY in clinical trials [see Adverse Reactions (6)]. After initiation of WEGOVY,
`
`
`
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`MPI EXHIBIT 1106 PAGE 5
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`

`

`
`
`
`
`
`
` observe patients carefully for signs and symptoms of acute pancreatitis (including persistent severe abdominal
`
` pain, sometimes radiating to the back, and which may or may not be accompanied by vomiting). If acute
`
` pancreatitis is suspected, WEGOVY should promptly be discontinued, and appropriate management should be
`
`
`
` initiated. If acute pancreatitis is confirmed, WEGOVY should not be restarted.
`
`
`
`
`
`
`
`
`
`There is limited experience from clinical trials with WEGOVY in patients with a history of pancreatitis. It is
`
`unknown if patients with a history of pancreatitis are at higher risk for development of pancreatitis on
`
`WEGOVY.
`
`
`
`5.3
`Acute Gallbladder Disease
`
`
`Treatment with WEGOVY is associated with an increased occurrence of cholelithiasis and cholecystitis. The
`
`
`
`incidence of cholelithiasis and cholecystitis was higher in WEGOVY-treated pediatric patients aged 12 years
`
`
`
`
`
`and older than in WEGOVY-treated adults. In randomized clinical trials in adult patients, cholelithiasis was
`
`
`
`reported by 1.6% of WEGOVY-treated patients and 0.7% of placebo-treated patients. Cholecystitis was
`
`
`
`
`
`
`
`
`
`reported by 0.6% of WEGOVY-treated adult patients and 0.2% of placebo-treated patients. In a clinical trial in
`
`pediatric patients aged 12 years and older, cholelithiasis was reported by 3.8% of WEGOVY-treated patients
`
`and 0% placebo-treated patients. Cholecystitis was reported by 0.8% of WEGOVY-treated pediatric patients
`
`and 0% placebo-treated patients [see Adverse Reactions (6.1)].
`
`
`
`
`Substantial or rapid weight loss can increase the risk of cholelithiasis; however, the incidence of acute
`
`
`
`gallbladder disease was greater in WEGOVY-treated patients than in placebo-treated patients, even after
`
`accounting for the degree of weight loss. If cholelithiasis is suspected, gallbladder studies and appropriate
`
`clinical follow-up are indicated.
`
`
`
`5.4 Hypoglycemia
`
`
`WEGOVY lowers blood glucose and can cause hypoglycemia.
`
`In a trial of adult patients with type 2 diabetes and body mass index (BMI) greater than or equal to 27 kg/m2,
`
`
`
`
`
`
`
`
`
`
`
`
`
`hypoglycemia (defined as a plasma glucose less than 54 mg/dL) was reported in 6.2% of WEGOVY-treated
`
`
`
`patients versus 2.5% of placebo-treated patients. One episode of severe hypoglycemia (requiring the assistance
`
`
`of another person) was reported in one WEGOVY-treated patient versus no placebo-treated patients.
`
`
`
`
`
`
`
`Patients with diabetes mellitus taking WEGOVY in combination with insulin or an insulin secretagogue (e.g.,
`
`
`
`
`
`sulfonylurea) may have an increased risk of hypoglycemia, including severe hypoglycemia. Hypoglycemia has
`
`
`been observed in patients treated with semaglutide at doses of 0.5 and 1 mg in combination with insulin. The
`
`
`
`
`
`use of WEGOVY (semaglutide 2.4 mg or 1.7 mg once weekly) in patients with type 1 diabetes mellitus or in
`
`combination with insulin has not been evaluated.
`
`
`
`
`Inform patients of the risk of hypoglycemia and educate them on the signs and symptoms of hypoglycemia. In
`
`
`patients with diabetes, monitor blood glucose prior to starting WEGOVY and during WEGOVY treatment.
`
`
`
`When initiating WEGOVY, consider reducing the dose of concomitantly administered insulin or insulin
`
`
`
`secretagogue (such as sulfonylureas) to reduce the risk of hypoglycemia [see Drug Interactions (7)].
`
`
`
`Acute Kidney Injury
`5.5
`
`There have been postmarketing reports of acute kidney injury and worsening of chronic renal failure, which
`
`
`
`have in some cases required hemodialysis, in patients treated with semaglutide. Patients with renal impairment
`
`
`
`may be at greater risk of acute kidney injury, but some of these events have been reported in patients without
`
`known underlying renal disease. A majority of the reported events occurred in patients who had experienced
`
`
`
`nausea, vomiting, or diarrhea, leading to volume depletion [see Adverse Reactions (6)].
`
`
`
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`Reference ID: 5342984
`
`MPI EXHIBIT 1106 PAGE 6
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`

`

`Monitor renal function when initiating or escalating doses of WEGOVY in patients reporting severe adverse
`
`
`
`
`
`gastrointestinal reactions. Monitor renal function in patients with renal impairment reporting any adverse
`
`reactions that could lead to volume depletion.
`
`
`5.6 Hypersensitivity
`
`
`Serious hypersensitivity reactions (e.g., anaphylaxis, angioedema) have been reported with WEGOVY. If
`
`hypersensitivity reactions occur, discontinue use of WEGOVY, treat promptly per standard of care, and monitor
`
`
`
`
`
`
`until signs and symptoms resolve. WEGOVY is contraindicated in patients with a prior serious hypersensitivity
`
`
`reaction to semaglutide or to any of the excipients in WEGOVY [see Adverse Reactions (6.2)].
`
`
`
`Anaphylaxis and angioedema have been reported with other GLP-1 receptor agonists. Use caution in a patient
`
`
`with a history of anaphylaxis or angioedema with another GLP-1 receptor agonist because it is unknown
`whether such patients will be predisposed to these reactions with WEGOVY.
`
`
`
`Diabetic Retinopathy Complications in Patients with Type 2 Diabetes
`5.7
`
`
`
`
`In a trial of adult patients with type 2 diabetes and BMI greater than or equal to 27 kg/m2, diabetic retinopathy
`
`
`
`
`
`
`
`
`
`was reported by 4.0% of WEGOVY-treated patients and 2.7% placebo-treated patients.
`
`
`
`
`
`In a 2-year trial with semaglutide 0.5 mg and 1 mg once-weekly injection in adult patients with type 2 diabetes
`
`and high cardiovascular risk, diabetic retinopathy complications (which was a 4-component adjudicated
`
`endpoint) occurred in patients treated with semaglutide injection (3.0%) compared to placebo (1.8%). The
`
`absolute risk increase for diabetic retinopathy complications was larger among patients with a history of
`
`
`diabetic retinopathy at baseline (semaglutide injection 8.2%, placebo 5.2%) than among patients without a
`
`known history of diabetic retinopathy (semaglutide injection 0.7%, placebo 0.4%).
`
`Rapid improvement in glucose control has been associated with a temporary worsening of diabetic retinopathy.
`
`The effect of long-term glycemic control with semaglutide on diabetic retinopathy complications has not been
`
`studied. Patients with a history of diabetic retinopathy should be monitored for progression of diabetic
`
`retinopathy.
`
`
`
`5.8 Heart Rate Increase
`
`Treatment with WEGOVY was associated with increases in resting heart rate. Mean increases in resting heart
`
`
`rate of 1 to 4 beats per minute (bpm) were observed in WEGOVY-treated adult patients compared to placebo in
`
`
`
`
`
`clinical trials. More adult patients treated with WEGOVY compared with placebo had maximum changes from
`
`baseline at any visit of 10 to 19 bpm (41% versus 34%, respectively) and 20 bpm or more (26% versus 16%,
`
`
`respectively). In a clinical trial in pediatric patients aged 12 years and older with normal baseline heart rate,
`
`
`more patients treated with WEGOVY compared to placebo had maximum changes in heart rate of 20 bpm or
`
`
`more (54% versus 39%) [see Adverse Reactions (6.1)].
`
`
`
`
`
`
`
`Monitor heart rate at regular intervals consistent with usual clinical practice. Instruct patients to inform their
`
`
`
`
`
`healthcare providers of palpitations or feelings of a racing heartbeat while at rest during WEGOVY treatment. If
`
`
`
`
`patients experience a sustained increase in resting heart rate, discontinue WEGOVY.
`
`
`
`
`Suicidal Behavior and Ideation
`5.9
`
`Suicidal behavior and ideation have been reported in clinical trials with other weight management products.
`
`
`
`
`
`Monitor patients treated with WEGOVY for the emergence or worsening of depression, suicidal thoughts or
`
`
`
`
`
`behavior, and/or any unusual changes in mood or behavior. Discontinue WEGOVY in patients who experience
`
`
`suicidal thoughts or behaviors. Avoid WEGOVY in patients with a history of suicidal attempts or active
`
`suicidal ideation.
`
`
`
`6
`ADVERSE REACTIONS
`
`
`
`The following serious adverse reactions are described below or elsewhere in the prescribing information:
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`Reference ID: 5342984
`
`MPI EXHIBIT 1106 PAGE 7
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`

`

` • Risk of Thyroid C-Cell Tumors [see Warnings and Precautions (5.1)]
`
`
` • Acute Pancreatitis [see Warnings and Precautions (5.2)]
`
`
`
`
` • Acute Gallbladder Disease [see Warnings and Precautions (5.3)]
`
`
` • Hypoglycemia [see Warnings and Precautions (5.4)]
`
`
`
`
`
` • Acute Kidney Injury [see Warnings and Precautions (5.5)]
`
`
` • Hypersensitivity Reactions [see Warnings and Precautions (5.6)]
`
`
`
`
` • Diabetic Retinopathy Complications in Patients with Type 2 Diabetes [see Warnings and Precautions
`
`
`
`
`(5.7)]
`
` • Heart Rate Increase [see Warnings and Precautions (5.8)]
`
`
` • Suicidal Behavior and Ideation [see Warnings and Precautions (5.9)]
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`6.1
`Clinical Trials Experience
`
`
`
`Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the
`
`clinical trials of a drug cannot be directly compared to rates in the clinical studies of another drug and may not
`
`reflect the rates observed in practice.
`
`
`Adverse Reactions in Clinical Trials in Adults with Obesity or Overweight
`
`
`WEGOVY 2.4 mg Subcutaneous Weekly Dosage
`
`
`
`WEGOVY was evaluated for safety in 3 randomized, double-blind, placebo-controlled trials that included 2,116
`
`
`
`
`
`adult patients with obesity or overweight treated with 2.4 mg WEGOVY for up to 68 weeks and a 7 week off-
`
`
`
`drug follow-up period [see Clinical Studies (14.2)]. Baseline characteristics included a mean age of 48 years,
`
`71% female, 72% White, 14% Asian, 9% Black or African American, and 5% reported as other or unknown;
`
`
`
`
`
`and 85% were not Hispanic or Latino ethnicity, 13% were Hispanic or Latino ethnicity, and 2% reported as
`
`
`
`unknown. The baseline characteristics were 42% with hypertension, 19% with type 2 diabetes, 43% with
`dyslipidemia, 28% with a BMI greater than 40 kg/m2, and 4% with cardiovascular disease.
`
`
`
`
`
`
`
`
`
`In these clinical trials, 6.8% of patients treated with 2.4 mg WEGOVY and 3.2% of patients treated with
`
`
`
`placebo permanently discontinued treatment as a result of adverse reactions. The most common adverse
`
`
`
`reactions leading to discontinuation were nausea (1.8% versus 0.2%), vomiting (1.2% versus 0%), and diarrhea
`
`
`
`
`(0.7% versus 0.1%) for WEGOVY and placebo, respectively.
`
`
`
`
`Adverse reactions reported in clinical trials in adults and greater than or equal to 2% of WEGOVY-treated
`
`patients and more frequently than in placebo-treated patients are shown in Table 3.
`
`
`
`
`
`
`Table 3. Adverse Reactions (> 2% and Greater Than Placebo) in WEGOVY-treated Adults with
`
`Obesity or Overweight
`
`
`
`
`
`
` Nausea
`
` Diarrhea
`
` Vomiting
`
` Constipation
`
` Abdominal Paina
`
` Headache
`
` Fatigueb
`
` Dyspepsia
`
` Dizziness
` Abdominal Distension
`
` Eructation
`Hypoglycemia in T2DMc
`
`
`
`
`
`Reference ID: 5342984
`
`
` Placebo
` N = 1,261
`
`
` %
`
` 16
`
` 16
`
` 6
`
` 11
`
` 10
`
` 10
`
` 5
`
` 3
`
` 4
`
` 5
`
` <1
`
` 2
`
`
`
`
` WEGOVY 2.4 mg
` N = 2,116
`
`
` %
`
` 44
`
` 30
`
` 24
`
` 24
`
` 20
`
` 14
`
` 11
`
` 9
`
` 8
`
` 7
`
` 7
`
` 6
`
`MPI EXHIBIT 1106 PAGE 8
`
`

`

`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` WEGOVY 2.4 mg
`
`
` Placebo
`
`
` N = 2,116
` N = 1,261
`
` %
`
`
` %
` Flatulence
`
`
` 6
`
` 4
` Gastroenteritis
`
`
` 6
`
` 4
` Gastroesophageal Reflux Disease
`
` 5
`
` 3
`
` Gastritisd
`
` 4
`
` 1
` Gastroenteritis Viral
`
` 4
`
` 3
`
` Hair Loss
`
` 3
`
` 1
` Dysesthesiae
`
`
` 2
`
` 1
` aIncludes abdominal pain, abdominal pain upper, abdominal pain lower, gastrointestinal pain, abdominal tenderness, abdominal
`
` discomfort and epigastric discomfort
`
`
`
`bIncludes fatigue and asthenia
`cDefined as blood glucose <54 mg/dL with or without symptoms of hypoglycemia or severe hypoglycemia (requiring the
`
`
`
`
`
`
`
`assistance of another person) in patients with type 2 diabetes not on concomitant insulin (Study 3, WEGOVY N=403, Placebo
`
`
`
`N=402). See text below for further information regarding hypoglycemia in patients with and without type 2 diabetes. T2DM =
`
`
`
`type 2 diabetes mellitus
`
`dIncludes chronic gastritis, gastritis, gastritis erosive, and reflux gastritis
`
`eIncludes paresthesia, hyperesthesia, burning sensation, allodynia, dysesthesia, skin burning sensation, pain of skin, and
`
`sensitive skin
`
`
` In a cardiovascular outcomes trial, 8,803 patients were exposed to WEGOVY for a median of 37.3 months and
`
`
`
`
`
`
`
`
`
`
`
`
`
` 8,801 patients were exposed to placebo for a median of 38.6 months [see Clinical Studies (14.1)]. Safety data
` collection was limited to serious adverse events (including death), adverse events leading to discontinuation,
`
`
`
`
`
` and adverse events of special interest. Sixteen percent (16%) of WEGOVY-treated patients and 8% of placebo-
` treated patients, respectively, discontinued study drug due to an adverse event. Additional information from this
`
`
`
`
`
`
` trial is included in subsequent sections below when relevant.
`
`Adverse Reactions in a Clinical Trial of Pediatric Patients Aged 12 Years and Older with Obesity
`
` WEGOVY was evaluated in a 68-week, double-blind, randomized, parallel group, placebo-controlled, multi-
`
` center trial in 201 pediatric patients aged 12 years and older with obesity [see Clinical Studies (14.3)]. Baseline
`
`
` characteristics included a mean age of 15.4 years; 38% of patients were male; 79% were White, 8% were Black
`
`
`
` or African American, 2% were Asian, and 11% were of other or unknown race; and 11% were of Hispanic or
`
`
`
`
`
` Latino ethnicity. The mean baseline body weight was 107.5 kg, and mean BMI was 37 kg/m2.
`
`
`Table 4 shows adverse reactions reported in greater than or equal to 3% of WEGOVY-treated pediatric patients
`
`
`
`and more frequently than in the placebo group from a study in pediatric patients aged 12 years and older.
`
`
`Table 4.
`
`
`Adverse Reactions (≥ 3% and Greater than