Baqsimi

1 INDICATIONS AND USAGE BAQSIMI™ is indicated for the treatment of severe hypoglycemia in adult and pediatric patients with diabetes ages 4 years and above. BAQSIMI™ is an antihypoglycemic agent indicated for the treatment of severe hypoglycemia in adult and pediatric patients with diabetes ages 4 years and above. ( 1 )

6 ADVERSE REACTIONS The following serious adverse reactions are described below and elsewhere in labeling: Hypersensitivity and Allergic Reactions [see Warnings and Precautions ( 5.3 )] . Most common (≥10%) adverse reactions associated with BAQSIMI are nausea, vomiting, headache, upper respiratory tract irritation (i.e., rhinorrhea, nasal discomfort, nasal congestion, cough, and epistaxis), watery eyes, redness of eyes, itchy nose, throat and eyes. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Eli Lilly and Company at 1-800-LillyRx (1-800-545-5979) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trial Data Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of BAQSIMI cannot be directly compared with rates in clinical trials of other drugs and may not reflect the rates observed in practice. Adverse Reactions in Adult Patients Two similarly designed comparator-controlled trials, Study 1 and Study 2, evaluated the safety of a single dose of BAQSIMI compared to a 1 mg dose of intra-muscular glucagon (IMG) in adult patients with diabetes [see Clinical Studies ( 14 )]. Table 1 presents adverse reactions that occurred with BAQSIMI at an incidence of ≥2% in a pool of Study 1 and Study 2. Table 1: Pooled Adverse Reactions (≥2%) in Adult Patients with Type 1 and Type 2 Diabetes in Study 1 and Study 2 a Upper Respiratory Tract Irritation: rhinorrhea, nasal discomfort, nasal congestion, cough, and epistaxis. Adverse Reaction BAQSIMI 3 mg (N=153) % Nausea 26.1 Headache 18.3 Vomiting 15.0 Upper Respiratory Tract Irritation a 12.4 Nasal and ocular symptoms with BAQSIMI were solicited through a patient questionnaire in Study 1 and 2 and these adverse reactions are presented in Table 2 . Table 2: Solicited Nasal and Non-Nasal Adverse Reactions in Adult Patients with Type 1 and Type 2 Diabetes Pooled from Study 1 and 2 a Subjects were asked to report whether they have the symptom, as well as severity (mild, moderate, severe) at baseline, and after glucagon administration. Adverse Reaction a BAQSIMI 3 mg (n=153) % Any increase in symptom severity a Watery eyes 58.8 Nasal congestion 42.5 Nasal itching 39.2 Runny nose 34.6 Redness of eyes 24.8 Itchy eyes 21.6 Sneezing 19.6 Itching of throat 12.4 Itching of ears 3.3 Adverse Reactions in Pediatric Patients Aged 4 Years and Above A single dose of BAQSIMI was compared to weight-based doses of 0.5 mg or 1 mg of IMG in pediatric patients with type 1 diabetes in Study 3 [see Clinical Studies ( 14 )]. Table 3 presents adverse reactions that occurred with BAQSIMI in pediatric patients at an incidence of ≥2% in Study 3. Table 3: Adverse Reactions (≥2%) Occurring in Pediatric Patients with Type 1 Diabetes in Study 3 a Upper Respiratory Tract Irritation: nasal discomfort, nasal congestion, sneezing. Adverse Reaction BAQSIMI 3 mg (n=36) % Vomiting 30.6 Headache 25.0 Nausea 16.7 Upper Respiratory Tract Irritation a 16.7 Nasal and ocular symptoms with BAQSIMI were solicited through a patient questionnaire in pediatric patients in Study 3 and these adverse reactions are presented in Table 4 . Table 4: Solicited Nasal and Non-Nasal Adverse Reactions in Pediatric Patients with Type 1 Diabetes in Study 3 a Subjects were asked to report whether they have the symptom, as well as severity (mild, moderate, severe) at baseline, and after glucagon administration. Adverse Reaction a BAQSIMI 3 mg (n=36) % Any increase in symptom severity a Watery eyes 47.2 Nasal congestion 41.7 Nasal itching 27.8 Runny nose 25.0 Sneezing 19.4 Itchy eyes 16.7 Redness of eyes 13.9 Itching of throat 2.8 Itching of ears 2.8 Other Adverse Reactions in Adult and Pediatric Patients Other observed adverse reactions with BAQSIMI-treated patients across clinical trials were, dysgeusia, pruritus, tachycardia, hypertension, and additional upper respiratory tract irritation events (nasal pruritus, throat irritation, and parosmia). 6.2 Immunogenicity As with all therapeutic peptides, there is the potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of incidence of antibodies to BAQSIMI with the incidences of antibodies to other products may be misleading. In 3 clinical trials, 3/124 (2%) of BAQSIMI-treated patients had treatment-emergent anti-drug antibodies as detected by an affinity capture elution (ACE) ligand-binding immunogenicity assay. No neutralizing antibodies were detected.

4 CONTRAINDICATIONS BAQSIMI is contraindicated in patients with: Pheochromocytoma because of the risk of substantial increase in blood pressure [see Warnings and Precautions ( 5.1 )] Insulinoma because of the risk of hypoglycemia [see Warnings and Precautions ( 5.2 )] Known hypersensitivity to glucagon or to any of the excipients in BAQSIMI. Allergic reactions have been reported with glucagon and include anaphylactic shock with breathing difficulties and hypotension [see Warnings and Precautions ( 5.3 )] Pheochromocytoma ( 4 ) Insulinoma ( 4 ) Known hypersensitivity to glucagon or to any of the excipients ( 4 )

11 DESCRIPTION BAQSIMI contains glucagon, an antihypoglycemic agent used to treat severe hypoglycemia. Glucagon is a single-chain polypeptide containing 29 amino acid residues and has a molecular weight of 3483, and is identical to human glucagon. Its molecular formula is C 153 H 225 N 43 O 49 S, with the following molecular structure: BAQSIMI is a preservative-free, white powder for intranasal administration in an intranasal device containing one dose of 3 mg glucagon. BAQSIMI contains glucagon as the active ingredient and betadex, and dodecylphosphocholine as the excipients. Molecular Structure

2 DOSAGE AND ADMINISTRATION BAQSIMI is for intranasal use only. ( 2.1 ) The recommended dose of BAQSIMI is 3 mg administered as one actuation of the intranasal device into one nostril. ( 2.2 ) Administer BAQSIMI according to the printed instructions on the shrink-wrapped tube label and the Instructions for Use. ( 2.1 ) Administer the dose by inserting the tip into one nostril and pressing the device plunger all the way in until the green line is no longer showing. The dose does not need to be inhaled. ( 2.1 ) Call for emergency assistance immediately after administering the dose. ( 2.1 ) When the patient responds to treatment, give oral carbohydrates. ( 2.1 ) Do not attempt to reuse BAQSIMI. Each BAQSIMI device contains one dose of glucagon and cannot be reused. ( 2.1 ) If there has been no response after 15 minutes, an additional 3 mg dose may be administered while waiting for emergency assistance. ( 2.2 ) 2.1 Important Administration Instructions BAQSIMI is for intranasal use only. Instruct patients and their caregivers on the signs and symptoms of severe hypoglycemia. Because severe hypoglycemia requires help of others to recover, instruct the patient to inform those around them about BAQSIMI and its Instructions for Use. Administer BAQSIMI as soon as possible when severe hypoglycemia is recognized. Instruct the patient or caregiver to read the Instructions for Use at the time they receive a prescription for BAQSIMI. Emphasize the following instructions to the patient or caregiver: Do not push the plunger or test the device prior to administration. Administer BAQSIMI according to the printed instructions on the shrink-wrapped tube label and the Instructions for Use. Administer the dose by inserting the tip into one nostril and pressing the device plunger all the way in until the green line is no longer showing. The dose does not need to be inhaled. Call for emergency assistance immediately after administering the dose. When the patient responds to treatment, give oral carbohydrates to restore the liver glycogen and prevent recurrence of hypoglycemia. Do not attempt to reuse BAQSIMI. Each BAQSIMI device contains one dose of glucagon and cannot be reused. 2.2 Dosage in Adults and Pediatric Patients Aged 4 Years and Above The recommended dose of BAQSIMI is 3 mg administered as one actuation of the intranasal device into one nostril. If there has been no response after 15 minutes, an additional 3 mg dose of BAQSIMI from a new device may be administered while waiting for emergency assistance.

10 OVERDOSAGE If overdosage occurs, the patient may experience nausea, vomiting, inhibition of GI tract motility, increase in blood pressure and pulse rate. In case of suspected overdosing, serum potassium levels may decrease and should be monitored and corrected if needed. If the patient develops a dramatic increase in blood pressure, phentolamine mesylate has been shown to be effective in lowering blood pressure for the short time that control would be needed.

7 DRUG INTERACTIONS Beta-blockers : Patients taking beta-blockers may have a transient increase in pulse and blood pressure. ( 7.1 ) Indomethacin : In patients taking indomethacin BAQSIMI may lose its ability to raise glucose or may produce hypoglycemia. ( 7.2 ) Warfarin : BAQSIMI may increase the anticoagulant effect of warfarin. ( 7.3 ) 7.1 Beta-blockers Patients taking beta-blockers may have a transient increase in pulse and blood pressure when given BAQSIMI. 7.2 Indomethacin In patients taking indomethacin, BAQSIMI may lose its ability to raise blood glucose or may even produce hypoglycemia. 7.3 Warfarin BAQSIMI may increase the anticoagulant effect of warfarin.

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Glucagon increases blood glucose concentration by activating hepatic glucagon receptors, thereby stimulating glycogen breakdown and release of glucose from the liver. Hepatic stores of glycogen are necessary for glucagon to produce an antihypoglycemic effect. 12.2 Pharmacodynamics After administration of BAQSIMI in adult patients with diabetes, the mean maximum glucose increase from baseline was 140 mg/dL ( Figure 1 ). In pediatric patients with type 1 diabetes (4 to <17 years), the mean maximum glucose increase from baseline was 138 mg/dL (4 to <8 years), 133 mg/dL (8 to <12 years), and 102 mg/dL (12 to <17 years) ( Figure 2 ). Sex and body weight had no clinically meaningful effects on the pharmacodynamics of BAQSIMI. Common cold with nasal congestion tested with or without use of decongestant did not impact pharmacodynamics of BAQSIMI. Figure 1 Mean glucose concentration over time after glucagon dose in adult Type 1 Diabetes patients with insulin-induced hypoglycemia. Figure 2 Mean glucose concentration over time in pediatric Type 1 Diabetes patients administered BAQSIMI Figure Figure 12.3 Pharmacokinetics Absorption Glucagon absorption via the intranasal route, achieved mean peak plasma levels of 6130 pg/mL at around 15 minutes. Distribution The apparent volume of distribution was approximately 885 L. Elimination The median half-life was approximately 35 minutes. Metabolism Glucagon is known to be degraded in the liver, kidneys, and plasma. Specific Populations Pediatrics In pediatric patients (4 to <17 years), glucagon via the intranasal route, achieved mean peak plasma levels between 15 and 20 minutes. The median half-life was 21 to 31 minutes. Patients with Colds Common cold with nasal congestion did not impact the pharmacokinetics of BAQSIMI. Drug Interaction Studies Common cold with use of decongestant did not impact the pharmacokinetics of BAQSIMI.

12.1 Mechanism of Action Glucagon increases blood glucose concentration by activating hepatic glucagon receptors, thereby stimulating glycogen breakdown and release of glucose from the liver. Hepatic stores of glycogen are necessary for glucagon to produce an antihypoglycemic effect.

12.2 Pharmacodynamics After administration of BAQSIMI in adult patients with diabetes, the mean maximum glucose increase from baseline was 140 mg/dL ( Figure 1 ). In pediatric patients with type 1 diabetes (4 to <17 years), the mean maximum glucose increase from baseline was 138 mg/dL (4 to <8 years), 133 mg/dL (8 to <12 years), and 102 mg/dL (12 to <17 years) ( Figure 2 ). Sex and body weight had no clinically meaningful effects on the pharmacodynamics of BAQSIMI. Common cold with nasal congestion tested with or without use of decongestant did not impact pharmacodynamics of BAQSIMI. Figure 1 Mean glucose concentration over time after glucagon dose in adult Type 1 Diabetes patients with insulin-induced hypoglycemia. Figure 2 Mean glucose concentration over time in pediatric Type 1 Diabetes patients administered BAQSIMI Figure Figure

12.3 Pharmacokinetics Absorption Glucagon absorption via the intranasal route, achieved mean peak plasma levels of 6130 pg/mL at around 15 minutes. Distribution The apparent volume of distribution was approximately 885 L. Elimination The median half-life was approximately 35 minutes. Metabolism Glucagon is known to be degraded in the liver, kidneys, and plasma. Specific Populations Pediatrics In pediatric patients (4 to <17 years), glucagon via the intranasal route, achieved mean peak plasma levels between 15 and 20 minutes. The median half-life was 21 to 31 minutes. Patients with Colds Common cold with nasal congestion did not impact the pharmacokinetics of BAQSIMI. Drug Interaction Studies Common cold with use of decongestant did not impact the pharmacokinetics of BAQSIMI.

20241113

7

3 DOSAGE FORMS AND STRENGTHS Nasal Powder: 3 mg glucagon: as a white powder in an intranasal device containing one dose of glucagon Nasal powder: intranasal device containing one dose of glucagon 3 mg ( 3 )

Baqsimi glucagon glucagon glucagon Betadex Dodecylphosphocholine Water Acetic Acid

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Long term studies in animals to evaluate carcinogenic potential have not been performed. Recombinant glucagon was positive in the bacterial Ames assay. It was determined that an increase in colony counts was related to technical difficulties in running this assay with peptides. Studies in rats have shown that glucagon does not cause impaired fertility.

13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Long term studies in animals to evaluate carcinogenic potential have not been performed. Recombinant glucagon was positive in the bacterial Ames assay. It was determined that an increase in colony counts was related to technical difficulties in running this assay with peptides. Studies in rats have shown that glucagon does not cause impaired fertility.

NDA210134

Baqsimi

glucagon

0002-6145

HUMAN PRESCRIPTION DRUG

NASAL

PACKAGE LABEL – Baqsimi 3 mg Nasal Powder Two Pack NDC 0002-6145-27 baqsimi TM (glucagon) nasal powder 3 mg For Treatment of Severe Low Blood Sugar For Nasal Use Only Contains 2 nasal devices. Keep tubes sealed until ready to use. Rx only BAQSIMI Two Pack TM www.baqsimi.com Lilly PACKAGE LABEL – Baqsimi 3 mg Nasal Powder Two Pack

17 PATIENT COUNSELING INFORMATION Advise the patient and family members or caregivers to read the FDA-approved patient labeling ( Patient Information and Instructions for Use ). Recognition of Severe Hypoglycemia: Inform patient and family members or caregivers on how to recognize the signs and symptoms of severe hypoglycemia and the risks of prolonged hypoglycemia. Administration: Review the Patient Information and Instructions for Use with the patient and family members or caregivers. Serious Hypersensitivity: Inform patients that allergic reactions can occur with BAQSIMI. Advise patients to seek immediate medical attention if they experience any symptoms of serious hypersensitivity reactions [see Warnings and Precautions ( 5.3 )] . Literature revised: October 2020 Marketed by: Lilly USA, LLC, Indianapolis, IN 46285, USA Copyright © 2019, 2020, Eli Lilly and Company. All rights reserved. BAQ-0002-USPI-20201027

INSTRUCTIONS FOR USE BAQSIMI™ (glucagon) nasal powder 3 mg Read the Instructions for Use for BAQSIMI before using it. BAQSIMI is used to treat very low blood sugar (severe hypoglycemia) that may cause you to need help from others. You should make sure you show your caregivers, family and friends where you keep BAQSIMI and explain how to use it by sharing these instructions. They need to know how to use BAQSIMI before an emergency happens. Tube and Device Parts Important Information to Know Do not remove the Shrink Wrap or open the Tube until you are ready to use it. If the Tube has been opened, BAQSIMI could be exposed to moisture. This could cause BAQSIMI not to work as expected. Do not push the plunger or test BAQSIMI before you are ready to use it. BAQSIMI contains 1 dose of glucagon nasal powder and cannot be reused. BAQSIMI is for nasal (nose) use only. BAQSIMI will work even if you have a cold or are taking cold medicine. Preparing the Dose Remove the Shrink Wrap by pulling on red stripe. Open the Lid and remove the Device from the Tube. Caution: Do not press the Plunger until ready to give the dose. Giving the Dose Hold Device between fingers and thumb. Do not push Plunger yet. Insert Tip gently into one nostril until finger(s) touch the outside of the nose. Push Plunger firmly all the way in. Dose is complete when the Green Line disappears. After giving BAQSIMI Call for emergency medical help right away. If the person is unconscious turn the person on their side. Throw away the used Device and Tube. Encourage the person to eat as soon as possible. When they are able to safely swallow, give the person a fast acting source of sugar, such as juice. Then encourage the person to eat a snack, such as crackers with cheese or peanut butter. If the person does not respond after 15 minutes, another dose may be given, if available. Storage and Handling Do not remove the Shrink Wrap or open the Tube until you are ready to use it. Store BAQSIMI in the shrink wrapped Tube at temperatures up to 86º F (30ºC ). Replace BAQSIMI before the expiration date printed on the Tube or carton. Other Information Caution: Replace the used BAQSIMI right away so you will have a new BAQSIMI in case you need it. Keep BAQSIMI and all medicines out of the reach of children. For Questions or More Information about BAQSIMI Call your healthcare provider Call Lilly at 1-800-Lilly-Rx (1-800-545-5979) Visit www.baqsimi.com BAQSIMI is a trademark of Eli Lilly and Company. Marketed by: Lilly USA, LLC Indianapolis, IN 46285, USA Copyright © 2019, Eli Lilly and Company. All rights reserved. BAQSIMI Device meets all applicable requirements defined in ISO 20072 This Instructions for Use has been approved by the U.S. Food and Drug Adminstration Issued: July 2019 BAQ-0001-IFU-20190724 Figure Figure Figure Figure Figure Figure Figure Figure

14 CLINICAL STUDIES 14.1 Adult Patients Study 1 (NCT03339453) was a randomized, multicenter, open-label, 2-period, crossover study in adult patients with type 1 diabetes. The efficacy of a single 3 mg dose of BAQSIMI was compared to a 1 mg dose of intra-muscular glucagon (IMG). Insulin was used to reduce blood glucose levels to <60 mg/dL. Seventy patients were enrolled, with a mean age of 41.7 years and a mean diabetes duration of 20.1 years. Twenty-seven (39%) were female. The primary efficacy outcome measure was the proportion of patients achieving treatment success, which was defined as either an increase in blood glucose to ≥70 mg/dL or an increase of ≥20 mg/dL from glucose nadir within 30 minutes after receiving study glucagon, without receiving additional actions to increase the blood glucose level. Glucose nadir was defined as the minimum glucose measurement at the time of, or within 10 minutes, following glucagon administration. The mean nadir blood glucose was 54.5 mg/dL for BAQSIMI and 55.8 mg/dL for IMG. BAQSIMI demonstrated non-inferiority to IMG in reversing insulin-induced hypoglycemia with 100% of BAQSIMI-treated patients and 100% of IMG-treated patients achieving treatment success. The mean time to treatment success was 11.6 and 9.9 minutes in the BAQSIMI and IMG 1 mg treatment groups, respectively. Table 5: Adult Patients with Type 1 Diabetes Meeting Treatment Success and Other Glucose Criteria in Study 1 a The Efficacy Analysis Population consisted of all patients who received both doses of the Study Drug with evaluable primary outcome. b Difference calculated as (percentage with success in BAQSIMI) – (percentage with success in IMG). c 2-sided 95% confidence interval (CI) of paired differences using a Wald-Min correction; non-inferiority margin = -10%. Type 1 Diabetes (N=66) a BAQSIMI 3 mg IMG 1 mg Treatment Success – n (%) 66 (100%) 66 (100%) Treatment Difference (2-sided 95% confidence limit) b, c 0% (-2.9%, 2.9%) Glucose criterion met – n (%) (i) ≥70 mg/dL (ii) Increase by ≥20 mg/dL from nadir Both (i) and (ii) 66 (100%) 66 (100%) 66 (100%) 66 (100%) 66 (100%) 66 (100%) Study 2 (NCT01994746) was a randomized, multicenter, open-label, 2-period, crossover study in adult patients with type 1 diabetes or type 2 diabetes. The efficacy of a single 3 mg dose of BAQSIMI was compared to a 1 mg dose of intra-muscular glucagon (IMG). Insulin was used to reduce blood glucose levels to the hypoglycemic range with a target blood glucose nadir of <50 mg/dL. Study 2 enrolled 83 patients 18 to <65 years of age. The mean age of patients with type 1 diabetes (N=77) was 32.9 years and a mean diabetes duration of 18.1 years, and 45 (58%) patients were female. The mean age of patients with type 2 diabetes (N=6) was 47.8 years, with a mean diabetes duration of 18.8 years, and 4 (67%) patients were female. The mean nadir blood glucose was 44.2 mg/dL for BAQSIMI and 47.2 mg/dL for IMG. BAQSIMI demonstrated non-inferiority to IMG in reversing insulin-induced hypoglycemia with 98.8% of BAQSIMI-treated patients and 100% of IMG-treated patients achieving treatment success within 30 minutes. The mean time to treatment success was 15.9 and 12.1 minutes in the BAQSIMI and IMG 1 mg treatment groups, respectively. Table 6: Adult Patients with Type 1 and Type 2 Diabetes Meeting Treatment Success and Other Glucose Criteria in Study 2 a The Efficacy Analysis Population consisted of all patients who received both doses of the Study Drug with evaluable primary outcome. b Difference calculated as (percentage with success in BAQSIMI) – (percentage with success in IMG). c 2-sided 95% confidence interval (CI) of paired differences using a Wald-Min correction; non-inferiority margin = -10%. d Percentage based on number of patients. Type 1 and Type 2 Diabetes (N=80) a BAQSIMI 3 mg IMG 1 mg Treatment Success – n (%) 79 (98.8%) 80 (100%) Treatment Difference (2-sided 95% confidence limit) b,c -1.3% (-4.6%, 2.2%) Glucose criterion met – n (%) d (i) ≥70 mg/dL 77 (96%) 79 (99%) (ii) Increase by ≥20 mg/dL from nadir 79 (99%) 80 (100%) Both (i) and (ii) 77 (96%) 79 (99%) 14.2 Pediatric Patients Study 3 (NCT01997411) was a randomized, multicenter, clinical study that assessed BAQSIMI compared to intra-muscular glucagon (IMG) in pediatric patients aged 4 years and older with type 1 diabetes. Insulin was used to reduce blood glucose levels, and glucagon was administered after glucose reached <80 mg/dL. Efficacy was assessed based on percentage of patients with a glucose increase of ≥20 mg/dL from glucose nadir within 30 minutes following BAQSIMI administration. Forty-eight patients were enrolled and received at least one dose of study drug. The mean age in the Young Children cohort (4 to <8 years) was 6.5 years. In the Children cohort (8 to <12 years), mean age was 11.1 years and in the Adolescents cohort (12 to <17 years) mean age was 14.6 years. In all age cohorts, the population was predominantly male and white. Across all age groups, all (100%) patients in both treatment arms achieved an increase in glucose ≥20 mg/dL from glucose nadir within 20 minutes of glucagon administration. The mean time to reach a glucose increase of ≥20 mg/dL for BAQSIMI and IMG for all age groups is shown in Table 7 . Table 7: Mean Time to Reach Glucose Increase of ≥20 mg/dL from Nadir in Pediatric Patients with Type 1 Diabetes in Study 3 Increase from Nadir Mean Time Post-Glucagon Administration (minutes) Young Children (4 to <8 years old) Children (8 to <12 years old) Adolescents (12 to <17 years old) IMG a N=6 BAQSIMI 3 mg N=12 IMG a N=6 BAQSIMI 3 mg N=12 IMG a N=12 BAQSIMI 3 mg N=12 a 0.5 mg or 1 mg of IMG (based upon body weight) ≥20 mg/dL 10.8 10.8 12.5 11.3 12.5 14.2

8.5 Geriatric Use Clinical studies of BAQSIMI did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Limited clinical trial experience has not identified differences in responses between the elderly and younger patients.

8.4 Pediatric Use The safety and effectiveness of BAQSIMI for the treatment of severe hypoglycemia in patients with diabetes have been established in pediatric patients ages 4 years and above. Use of BAQSIMI for this indication is supported by evidence from a study in 48 pediatric patients from 4 to <17 years of age with type 1 diabetes mellitus. [see Clinical Studies ( 14.2 )] . The safety and effectiveness of BAQSIMI have not been established in pediatric patients younger than 4 years of age.

8.1 Pregnancy Risk Summary Available data from case reports and a small number of observational studies with glucagon use in pregnant women over decades of use have not identified a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. Multiple small studies have demonstrated a lack of transfer of pancreatic glucagon across the human placental barrier during early gestation. In a rat reproduction study, no embryofetal toxicity was observed with glucagon administered by injection during the period of organogenesis at doses representing up to 40 times the human dose, based on body surface area (mg/m 2 ) (see Data). The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Data Animal Data In pregnant rats given animal sourced glucagon twice-daily by injection at doses up to 2 mg/kg (up to 40 times the human dose based on body surface area extrapolation, mg/m 2 ) during the period of organogenesis, there was no evidence of increased malformations or embryofetal lethality.

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Risk Summary Available data from case reports and a small number of observational studies with glucagon use in pregnant women over decades of use have not identified a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. Multiple small studies have demonstrated a lack of transfer of pancreatic glucagon across the human placental barrier during early gestation. In a rat reproduction study, no embryofetal toxicity was observed with glucagon administered by injection during the period of organogenesis at doses representing up to 40 times the human dose, based on body surface area (mg/m 2 ) (see Data). The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Data Animal Data In pregnant rats given animal sourced glucagon twice-daily by injection at doses up to 2 mg/kg (up to 40 times the human dose based on body surface area extrapolation, mg/m 2 ) during the period of organogenesis, there was no evidence of increased malformations or embryofetal lethality. 8.2 Lactation Risk Summary There is no information available on the presence of glucagon in human or animal milk, the effects of the drug on the breastfed infant, or the effects of the drug on milk production. However, glucagon is a peptide and would be expected to be broken down to its constituent amino acids in the infant's digestive tract and is therefore, unlikely to cause harm to an exposed infant. 8.4 Pediatric Use The safety and effectiveness of BAQSIMI for the treatment of severe hypoglycemia in patients with diabetes have been established in pediatric patients ages 4 years and above. Use of BAQSIMI for this indication is supported by evidence from a study in 48 pediatric patients from 4 to <17 years of age with type 1 diabetes mellitus. [see Clinical Studies ( 14.2 )] . The safety and effectiveness of BAQSIMI have not been established in pediatric patients younger than 4 years of age. 8.5 Geriatric Use Clinical studies of BAQSIMI did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Limited clinical trial experience has not identified differences in responses between the elderly and younger patients.

16 HOW SUPPLIED/STORAGE AND HANDLING BAQSIMI is supplied as an intranasal device containing one 3 mg dose of glucagon as a preservative free, white powder. BAQSIMI One Pack™ carton contains 1 intranasal device (NDC 0002-6145-11) BAQSIMI Two Pack™ carton contains 2 intranasal devices (NDC 0002-6145-27) Store at temperatures up to 86°F (30°C) in the shrink wrapped tube provided. Keep BAQSIMI in the shrink wrapped tube until ready to use. If the tube has been opened, BAQSIMI may have been exposed to moisture and may not work as expected. Discard BAQSIMI and tube after use.