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New Glucagon Products for Severe Hypoglycemia: Gvoke® and Baqsimi®

21 Jan 2021 6:04 PM | Anonymous

By: Abbey Jin, PharmD Candidate 2021, St. Louis College of Pharmacy at University of Health Sciences and Pharmacy in St. Louis

Mentor: Laura Challen, PharmD, MBA, BCPS, BCACP, Associate Professor, St. Louis College of Pharmacy at University of Health Sciences and Pharmacy in St. Louis; Clinical Pharmacist, JFK Clinic Mercy Hospital-St. Louis

Introduction

Severe hypoglycemia, a severe and potentially fatal event that requires intervention, has historically been treated with injectable glucagon that requires reconstitution prior to injection. Baqsimi® and Gvoke® are new United States Food and Drug Administration (FDA)-approved glucagon products for severe hypoglycemia that provide alternative preparations. Eli Lilly and Company’s Baqsimi® nasal powder is an intranasal glucagon delivery device, approved on July 24th, 2019.1 It is the first non-injectable glucagon therapy for emergency treatment in severe hypoglycemia.1 Xeris Pharmaceutical’s Gvoke® is a glucagon injection for treatment of severe hypoglycemia, approved on September 10th, 2019.2

Hypoglycemia Classifications

Hypoglycemia can be differentiated into three classifications: levels 1, 2, and 3. Level 1 (mild hypoglycemia) is defined as blood glucose levels greater than or equal to 54 mg/dL up to 69 mg/dL. Level 2 (moderate hypoglycemia) is defined as blood glucose levels less than 54 mg/dL. Level 3 (severe hypoglycemia) is defined as hypoglycemia that results in altered physical and/or mental state and needing intervention. It is recommended that any patients who experience level 2 or 3 hypoglycemia travel with a glucagon device3 for administration by a caregiver in case the patient becomes unresponsive.4 If the patient is conscious, glucose can be self-administered orally.4

Indication, Dosage, Administration, Storage and Cost

Baqsimi® is indicated for severe hypoglycemia treatment in patients with diabetes who are 4 years of age and older. It is designed to be absorbed via the nasal mucosa and does not need to be reconstituted prior to intranasal administration.3 The recommended dosage and route for all patients is 3 mg (one actuation) intranasally (in one nostril).5 A caretaker should insert the tip of the device into one nostril and press the plunger. After the dose is administered, the caregiver should call emergency medical services. If the patient does not respond to the first 3 mg dose, then another 3 mg dose from an un-used Baqsimi® device can be administered after 15 minutes.5 Baqsimi® is available as a carton containing one or two devices of a single 3 mg dose. It is recommended to store Baqsimi® devices at temperatures up to 86oF.3 Per Micromedex® Red Book, the wholesale acquisition cost (WAC) package price is $280.80 for the Baqsimi® One PackTM.6

Gvoke® is indicated for the treatment of severe hypoglycemia in patients with diabetes who are 2 years of age and older. Two Gvoke® products are available for use: Gvoke® pre-filled syringe (PFS) 0.5 mg/0.1 mL or 1 mg/0.2 mL and Gvoke® HypoPen 0.5 mg/0.1 mL or 1 mg/0.2 mL autoinjectors.7 Gvoke® products are dispensed as single doses and do not require reconstitution prior to administration.4 The recommended dose and route for patients 2 to under 12 years of age and who weigh less than 45 kg is 0.5 mg subcutaneously. The recommended dose and route for pediatric patients who weigh 45 kg and over or who are 12 years of age and older is 1 mg subcutaneously. Areas recommended for injection are the outer, upper arm, outer thigh, or lower abdomen. Similar to Baqsimi®, following a dose, emergency medical services should be called. If a patient is unresponsive after one dose, a second dose can be administered 15 minutes later.4 Gvoke® is to be stored at room temperatures ranging from 68oF to 77oF.7 Per Micromedex® Red Book, the WAC package price for the Gvoke® HypoPen and Gvoke® PFS 1 packs are both $280.80, the same price as Baqsimi®.8,9

Drug Interactions, Adverse Drug Events, Contraindications, Use in Pregnancy and Lactation

Gvoke® and Baqsimi® may interact with indomethacin, interfering with their ability to increase blood glucose. They also have potential drug interactions with beta-blockers, which can lead to increases in blood pressure and pulse. Gvoke® and Baqsimi® can increase warfarin’s anticoagulation effects.3,7

For Baqsimi®, the most common potential side effects include headache; vomiting and nausea; nasal discomfort and congestion; watery, itchy, or red eyes, and itchy throat.5 Gvoke®’s most common side effects for adults include headache, nausea, vomiting, and injection site edema. Gvoke®’s most common side effects for pediatric patients include headache, nausea, vomiting, pain in the abdomen, injection site reaction and discomfort, urticaria, and hypo- and hyperglycemia.10 Both are contraindicated in patients with a medical history of pheochromocytoma, insulinoma, and glucagon hypersensitivity.5,10

From case reports and observational studies, there has not been a reported link between administration of glucagon in pregnant women and risk of miscarriage, defects, or other negative outcomes for the fetus and mother.5,10 There is currently no data on glucagon being present in breast milk, but glucagon is hypothesized to be of no danger to infants since it can be broken down in their gastrointestinal tracts.3,7

Baqsimi® Clinical Trials Review

Intranasal glucagon has been studied in three clinical trials. In an open-label, randomized, crossover, and two-period trial, Suico et al. showed that all of the 66 type I diabetes mellitus (T1DM) patients who were administered intramuscular and nasal glucagon experienced a rise in the plasma glucose to at least 70 mg/dL or a rise of at least 20 mg/dL from baseline in 30 minutes of administration. The results showed that 3 mg nasal glucagon was non-inferior to 1 mg intramuscularly administered glucagon with a 0.0% treatment difference (-1.52%, 1.52%).11

Rickels et al. conducted a randomized, crossover, non-inferiority trial with 75 adult T1DM patients. The study showed that 98.7% of the 3 mg intranasal and 100% of the 1 mg intramuscular glucagon visits had a rise in plasma glucose to 70 mg/dL or greater or an increase by 20 mg/dL or greater from baseline within 30 minutes of administration (98.7% vs. 100%; CI 4.0%).12

Sherr et al. conducted a randomized, crossover trial studying the rise in blood glucose of T1DM patients (4 to less than 8 years of age and 8 to less than 12 years of age) who received either 2 or 3 mg intranasal glucagon at two different times vs. one weight-based dose of intramuscular glucagon. Children under 25 kg received a 0.5 mg dose. Children weighing at least 25 kg received a 1 mg dose. Sherr et al. also studied patients 12 to less than 17 years of age. They were administered a 1 mg intramuscular dose of glucagon during one time and a 3 mg intranasal glucagon at another time. The results showed that 58 out of 59 intranasal and all 24 intramuscular glucagon administrations resulted in a glucose rise greater than or equal to 25 mg/dL from baseline within 20 minutes of administration. The study supported use of 3 mg intranasal glucagon for pediatric patients ranging from 4 to less than 17 years. Intramuscular and intranasal glucagon administrations reported nausea at 67% and 42%, respectively (p=0.05).13

Gvoke® Clinical Trials Review

Gvoke® has been studied in 2 multicenter crossover studies of adult T1DM populations (18 to 74 years). One study was double-blinded with 80 participants. The other study was single blinded with 81 participants. A single-arm trial of 31 T1DM pediatric patients from 2 to under 18 years of age was also conducted. Nearly all (98.7%) of the adult patients that were administered Gvoke® and all (100% ) of the adult patients that were administered a Glucagon Emergency Kit® had a rise in blood glucose to more than 70 mg/dL or an increase of 20 mg/dL or more from baseline 30 minutes post administration. Gvoke®’s mean time to the aforementioned outcomes was 13.8 minutes while the Glucagon Emergency Kit® was 10 minutes. In the pediatric arm, 30 out of 30 (100%) of the evaluated patients experienced a rise of greater than or equal to 25 mg/dL in blood glucose.10

From the total of 154 adult patients who were administered Gvoke®, the most common adverse reactions were nausea, vomiting, edema at injection area, and headache. For the pediatric population (n=31), most common adverse reactions experienced by all age groups were nausea, hypoglycemia, and vomiting.10

Comparison with Previous Glucagon Products

Unlike previous glucagon injections, both Gvoke® and Baqsimi® do not require reconstitution prior to administration.3,4 This can result in saving precious minutes during the event of a severe hypoglycemic attack. This may also be easier for a caretaker to administer compared to GlucaGen® and Eli Lilly and Company’s glucagon due to lack of reconstitution. Preparation and administration of Gvoke® was also shorter by 60-70 seconds versus the Glucagon Emergency Kit®.4 Novo Nordisk’s GlucaGen® HypoKit®’s WAC package price is $293.05 each, slightly costlier than Baqsimi® and Gvoke®.14 Fresenius’s Glucagon Emergency Kit®’s WAC package price is $279.80 while Eli Lilly and Company’s Glucagon Emergency Kit®’s WAC package price is $280.80, comparable to Gvoke® and Baqsimi®.15

Conclusion

Gvoke® and Baqsimi® are new glucagon devices with shorter preparation time and comparable pricing to those currently available on the market.3-10,14,15 However, as with all new products, time will gauge their popularity and preference amongst patients with diabetes.

References:

  1. U.S. Food and Drug Administration. FDA approves first treatment for severe hypoglycemia that can be administered without an Injection. 2020. https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-severe-hypoglycemia-can-be-administered-without-injection. Accessed December 15, 2020.
  2. Drug Approval Package: GVOKE INJECTION. Accessdata.fda.gov. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212097Orig1s000TOC.cfm. Published 2020. Accessed December 15, 2020.
  3. Glucagon nasal powder (Baqsimi) for severe hypoglycemia. Med Lett Drugs Ther. 2019;61(1581):148-149.
  4. In brief: A new glucagon injection (Gvoke) for severe hypoglycemia. Med Lett Drugs Ther. 2019;61(1585):186.
  5. Baqsimi [Prescribing Information]. Indianapolis, IN: Eli Lilly and Company; 2019. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/210134s000lbl.pdf. Accessed December 15, 2020.
  6. Product Name: BAQSIMI. RED BOOK Online. IBM Micromedex [database online]. Truven Health Analytics/IBM Watson Health; 2020. Accessed December 15, 2020. https://www.micromedexsolutions.com
  7. National Institutes of Health/U.S. National Library of Science. DailyMed: GVOKE PFS 0.5 MG PRE-FILLED SYRINGE- Glucagon Injection, Solution Injection, Solution GVOKE PFS 1 MG PRE-FILLED SYRINGE- Glucagon Injection, Solution Injection, Solution GVOKE HYPOPEN 1 MG AUTO-INJECTOR- Glucagon Injection, Solution Injection, Solution GVOKE HYPOPEN 0.5 MG AUTO-INJECTOR- Glucagon Injection, Solution Injection, Solution. National Institutes of Health/U.S. National Library of Science; 2020.
  8. Product Name: GVOKE PFS 1 PACK. RED BOOK Online. IBM Micromedex [database online]. Truven Health Analytics/IBM Watson Health; 2020. Accessed December 15, 2020. https://www.micromedexsolutions.com
  9. Product Name: GVOKE HYPOPEN 1 PACK. RED BOOK Online. IBM Micromedex [database online]. Truven Health Analytics/IBM Watson Health; 2020. Accessed December 15, 2020. https://www.micromedexsolutions.com
  10. Gvoke [Prescribing Information]. Chicago, IL: Xeris Pharmaceuticals, Inc; 2019. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212097s000lbl.pdf. Accessed December 15, 2020.
  11. Suico JG, Hövelmann U, Zhang S, et al. Glucagon Administration by Nasal and Intramuscular Routes in Adults With Type 1 Diabetes During Insulin-Induced Hypoglycaemia: A Randomised, Open-Label, Crossover Study. Diabetes Ther. 2020;11(7):1591-1603. doi:10.1007/s13300-020-00845-7
  12. Rickels MR, Ruedy KJ, Foster NC, et al. Intranasal Glucagon for Treatment of Insulin-Induced Hypoglycemia in Adults With Type 1 Diabetes: A Randomized Crossover Noninferiority Study. Diabetes Care. 2016;39(2):264-270. doi:10.2337/dc15-1498
  13. Sherr JL, Ruedy KJ, Foster NC, et al. Glucagon Nasal Powder: A Promising Alternative to Intramuscular Glucagon in Youth With Type 1 Diabetes. Diabetes Care. 2016;39(4):555-562. doi:10.2337/dc15-1606
  14. Product Name: GLUCAGEN HYPOKIT. RED BOOK Online. IBM Micromedex [database online]. Truven Health Analytics/IBM Watson Health; 2020. Accessed December 15, 2020. https://www.micromedexsolutions.com
  15. Product Name: GLUCAGON EMERGENCY KIT. RED BOOK Online. IBM Micromedex [database online]. Truven Health Analytics/IBM Watson Health; 2020. Accessed December 15, 2020. https://www.micromedexsolutions.com


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