Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as G-Pen (glucagon injection), CSI-Glucagon (continuous subcutaneous glucagon infusion), G-Pen, G-Pump™ (glucagon infusion), Lilly Glucagon (glucagon injection [rDNA origin]), Glucagon RTU
glucagon · 10 trials · 8 indications
Number of subjects with an increase in plasma glucose concentration from below 54 mg/dL (3 mmol/L) to greater than 70 mg/dL (3.89 mmol/L) or an increase in plasma glucose concentration \> 20 mg/dL (\> 1.11 mmol/L) within 30 minutes after administration of glucagon
Increase in plasma glucose concentration from below 50.0 mg/dL to greater than 70.0 mg/dL within 30 minutes after receiving glucagon
The primary endpoint for this study is an evaluation of change in plasma glucose following treatment with G-Pen, with an emphasis on the increase from baseline to 30 minutes post-dosing.
Number of subjects with an increase in plasma glucose concentration from below 50 mg/dL to greater than 70 mg/dL within 30 minutes after administration of glucagon
Number of subjects with an increase in plasma glucose concentration from below 50 mg/dL to greater than 70 mg/dL within 30 minutes after administration of glucagon
Number of subjects with either an increase in plasma glucose concentration from below 50 mg/dL to greater than 70 mg/dL or an increase in from baseline in plasma glucose concentration of at least 20 mg/dL within 30 minutes after administration of glucagon
Mean incidence rate of hypoglycemia during and after sessions of moderate to high intensity aerobic exercise in 12-week Outpatient Phase. Incidence rate is defined as the number of hypoglycemic events divided by the total number of qualified exercise sessions, assessed at group level. Qualified exercise session is: (1) confirmed blood glucose of 100-180 mg/dL prior to start of exercise, (2) self-administered study drug no more than 10 min prior to exercise (5 min target), (3) conducted a protocol allowed exercise of moderate to high intensity for at least 30 min and no longer than 75 min, and (4) achieved a target heart rate of 80% of maximum calculated heart rate at least once during session. Exercise sessions were to occur at least 2-3 times per week. Only 1 qualified exercise session/subject/day was included in the analysis (the first if \>1). Hypoglycemic event defined as any hypoglycemic event occurring within 30 (+2) min after completion of a qualified exercise session.
Outpatient Phase: Mean number of hypoglycemic events associated with the qualified exercise sessions, assessed at group level. A qualified exercise session was defined as one were (1) a confirmed blood glucose value of 100-180 mg/dL prior to start of exercise, (2) self-administered the study drug no more than 10 minutes prior to exercise (5 minutes was the target), (3) conducted a protocol allowed exercise for moderate to high intensity for at least 30 minutes and no longer than 75 minutes, and (4) achieved a target heart rate of 80% of maximum calculated heart rate at least once during the session. A hypoglycemic event was defined as any hypoglycemic event occurring during or within 30 (+2) minutes after completion of a qualified exercise session. Exercise sessions were expected to occur at least 2 to 3 times per week. Only 1 qualified exercise session per subject per day was included in the analysis (the first if \>1).
Outpatient Phase: Mean number of qualified exercise sessions, assessed at group level. A qualified exercise session was defined as one were (1) a confirmed blood glucose value of 100-180 mg/dL prior to start of exercise, (2) self-administered the study drug no more than 10 minutes prior to exercise (5 minutes was the target), (3) conducted a protocol allowed exercise for moderate to high intensity for at least 30 minutes and no longer than 75 minutes, and (4) achieved a target heart rate of 80% of maximum calculated heart rate at least once during the session. Exercise sessions were expected to occur at least 2 to 3 times per week. Only 1 qualified exercise session per subject per day was included in the analysis (the first if \>1).
Number of subjects with blood glucose \> 70 mg/dL
Frequency of blood glucose \> 70 mg/dL
Change from baseline in glucose infusion rate (GIR) will be determined for each subject at 24 and 48 hours from the start of blinded treatment. Subjects with a decrease in GIR ≥ 20% at 24 hours, and ≥ 33% at 48 hours will be considered to have had a clinically meaningful treatment response.
For 90 minutes following treatment, plasma glucose was measured every 5 minutes, with an increase in plasma glucose to \>70 mg/dL within 30 minutes of treatment being considered a positive response.
Number of serious adverse events (SAEs) per treatment group
A primary endpoint for this study is the prevention of meal provoked hypoglycemia, defined as sensor glucose levels below \<65 mg/dl, comparing study drug to control.
A primary endpoint for this study is prevention of meal provoked hypoglycemia, defined as plasma glucose levels below \<65 mg/dl, comparing study drug to control
| Arm | Type | Description |
|---|---|---|
| G-Pen followed by Novo Glucagon | EXPERIMENTAL | 1 mg G-Pen at the first treatment visit followed by 1 mg Novo Glucagon at the second treatment visit |
| Novo Glucagon followed by G-Pen | ACTIVE_COMPARATOR | 1 mg Novo Glucagon at the first treatment visit followed by 1 mg G-Pen at the second treatment visit |
| G-Pen followed by Lilly Glucagon | OTHER | 1 mg G-Pen at the first treatment visit followed by 1 mg Lilly Glucagon at the second treatment visit |
| Lilly Glucagon followed by G-Pen | OTHER | 1 mg Lilly Glucagon at the first treatment visit followed by 1 mg G-Pen at the second treatment visit |
| G-Pen (glucagon injection) 0.5 mg | EXPERIMENTAL | A single 0.5 mg subcutaneous (SC) injection of G-Pen (glucagon injection) |
| G-Pen (glucagon injection) 1.0 mg | EXPERIMENTAL | A single 1.0 mg subcutaneous (SC) injection of G-Pen (glucagon injection) |
| G-Pen first, then Lilly Glucagon | OTHER | A single 1 mg subcutaneous (SC) injection of G-Pen (glucagon injection) with a 7-28 day wash-out, followed by a single 1 mg SC injection of Lilly Glucagon (glucagon injection \[rDNA origin\]) |
| Lilly Glucagon first, then G-Pen | OTHER | A single 1 mg SC injection of Lilly Glucagon (glucagon injection \[rDNA origin\]) with a 7-28 day wash-out, followed by a single 1 mg SC injection of G-Pen (glucagon injection) |
| CRC Phase: Glucagon RTU With Insulin Pump Reduction | EXPERIMENTAL | CRC Phase: 2-arm randomized double-blind crossover, Glucagon RTU Injection 30 microliters of 0.15 mg injection with 50% reduction in the insulin pump |
| CRC Phase: Vehicle for Glucagon RTU With Insulin Pump Reduction | PLACEBO_COMPARATOR | CRC Phase: 2-arm randomized double-blind crossover, Vehicle for Glucagon RTU Injection 30 microliters vehicle with 50% reduction in the insulin pump |
| Outpatient Phase: Glucagon RTU With Insulin Pump Reduction | EXPERIMENTAL | Outpatient Phase: 3-arm randomized comparison (2-arm double-blind, 1-arm open-label), Glucagon RTU Injection 30 microliters of 0.15 mg injection with 50% reduction in the insulin pump (double-blind arm) |
| Outpatient Phase: Vehicle for Glucagon RTU With Insulin Pump Reduction | PLACEBO_COMPARATOR | Outpatient Phase: 3-arm randomized comparison (2-arm double-blind, 1-arm open-label), Vehicle for Glucagon RTU Injection 30 microliters vehicle with 50% reduction in the insulin pump (double-blind arm) |
| Outpatient Phase: Glucagon RTU Without Insulin Pump Reduction | EXPERIMENTAL | Outpatient Phase: 3-arm randomized comparison (2-arm double-blind, 1-arm open-label), Glucagon RTU Injection 30 microliters of 0.15 mg injection without a reduction in the insulin pump (open-label arm) |
| Glucagon RTU (glucagon injection) | EXPERIMENTAL | Glucagon Ready-to-Use (RTU); 60 μL injection (0.3 mg glucagon) |
| Placebo | PLACEBO_COMPARATOR | Non-active vehicle for Glucagon RTU; 60 μL injection |
| CSI-Glucagon (Double-Blind Phase - 2 days) | EXPERIMENTAL | Glucagon solution delivered as a continuous subcutaneous infusion via a patch pump at a starting dosage of 5 mcg/kg/hr. |
| Placebo (Double-Blind Phase - 2 days) | PLACEBO_COMPARATOR | Vehicle solution delivered as a 24-hour continuous subcutaneous infusion via a patch pump. |
| CSI-Glucagon (Open-label Phase - Up to 28 days) | EXPERIMENTAL | Glucagon solution delivered as a continuous subcutaneous infusion via a patch pump at a starting dosage of 5 mcg/kg/hr. |
| Glucagon | EXPERIMENTAL | 1 mg G-Pen™ (glucagon injection) first, followed by 0.5 mg |
| G-Pen(TM) 1 mg | EXPERIMENTAL | G-Pen(TM) (glucagon injection), single 1 mg subcutaneous (SC) injection |
| G-Pen(TM) 0.5 mg | EXPERIMENTAL | G-Pen(TM) (glucagon injection), single 0.5 mg SC injection |
| Lilly Glucagon(TM) 1 mg | ACTIVE_COMPARATOR | Lilly Glucagon(TM) \[glucagon for injection (rDNA origin)\], single 1 mg SC injection |
| Study drug (glucagon) first, placebo second | OTHER | Each subject will have two mixed meal tolerance tests performed. Each will be randomized to receive either glucagon or matched placebo during the first testing session. A participant could receive 2 doses of the study drug or placebo at each study visit. The opposite treatment will be given during the second testing session after a 1-2 week washout period. Both participants and the study team will be blinded to the intervention being used during each session. |
| Placebo first, study drug (glucagon) second | OTHER | Each subject will have two mixed meal tolerance tests performed. Each will be randomized to receive either glucagon or matched placebo during the first testing session. A participant could receive 2 doses of the study drug or placebo at each study visit. The opposite treatment will be given during the second testing session after a 1-2 week washout period. Both participants and the study team will be blinded to the intervention being used during each session. |
| Name | Type | Description |
|---|---|---|
| G-Pen | DRUG | 1 mg subcutaneous injection of G-Pen (glucagon injection) administered via auto-injector |
| Novo Glucagon | DRUG | 1 mg subcutaneous injection of Novo Glucagon (glucagon injection) |
| Lilly Glucagon | DRUG | 1 mg subcutaneous injection of Lilly Glucagon (glucagon injection \[RNDA Origin\]) |
| Glucagon | DRUG | 0.5 or 1.0 mg of pre-mixed liquid Xeris glucagon delivered via auto-injector |
| G-Pen (glucagon injection) | DRUG | 1 mg of pre-mixed liquid Xeris glucagon delivered via auto-injector |
| Lilly Glucagon (glucagon injection [rDNA origin]) | DRUG | 1 mg of Lilly glucagon reconstituted from lyophilized powder |
| Glucagon RTU Injection With Insulin Pump Reduction | DRUG | 0.15 mg injection with 50% pump reduction |
| Vehicle for Glucagon RTU Injection With Insulin Pump Reduction | OTHER | vehicle injection with 50% pump reduction |
| Glugaon RTU Injection Without Insulin Pump Reduction | DRUG | 0.15 mg injection without pump reduction |
| Glucagon RTU | DRUG | Glucagon RTU is a sterile subcutaneous injectable non-aqueous solution formulation supplied in a vial and administered via syringe. |
| Placebo | OTHER | The placebo is a non-active version of Glucagon RTU formulation, containing the same solvent and excipients (i.e., vehicle). |
| G-Pen(TM) 1 mg | DRUG | - |
| Lilly Glucagon(TM) 1 mg | DRUG | - |
| G-Pen(TM) 0.5 mg | DRUG | - |
| Closed loop glucagon pump | DEVICE | a novel closed-loop glucagon system (CLG) incorporating a novel, stable non-aqueous glucagon formulation together with an infusion pump system (Omnipod) guided by real-time continuous glucose monitoring (Dexcom) that is triggered by a hypoglycemia alert algorithm. |
Inclusion Criteria: 1. Males and non-pregnant females diagnosed with type 1 diabetes (T1D) for at least 24 months. 2. Current usage of daily insulin treatment that includes having an assigned "correction factor" for managing hyperglycemia. 3. Age 18 to 75 years, inclusive. 4. Random serum C-peptide...
Glucagon is being developed for hypoglycemia and related endocrine conditions, including congenital hyperinsulinism, type 1 diabetes mellitus, hypoglycemia, and post-bariatric hypoglycemia. Xeris Biopharma Holdings, Inc. is developing the small molecule as a glucagon receptor agonist for these metabolic and glucose-control indications.
Glucagon targets GCGR, the glucagon receptor, and acts as an agonist. By activating this receptor, the drug is designed to raise blood glucose, which is the basis for its development in hypoglycemia, congenital hyperinsulinism, type 1 diabetes, and post-bariatric hypoglycemia.
Glucagon is being developed by Xeris Biopharma Holdings, Inc., which trades under the ticker XERS. The company is advancing the small molecule glucagon receptor agonist across several endocrine indications, including congenital hyperinsulinism, type 1 diabetes mellitus, hypoglycemia, and post-bariatric hypoglycemia.
Glucagon is in Phase 2 development. It is an investigational small molecule and is not described as approved. The clinical program includes completed trials across Phase 1, Phase 2, and Phase 3, with the Phase 2 work covering congenital hyperinsulinism and hypoglycemia rescue in type 1 diabetes.
Glucagon has been studied in completed trials including NCT03255629, a Phase 1 closed-loop glucagon pump study in post-bariatric hypoglycemia; NCT03091673, a Phase 3 glucose response study in pediatric type 1 diabetes; NCT02937558, a Phase 2 study in children with congenital hyperinsulinism; and NCT02423980, a Phase 2 hypoglycemia rescue study in type 1 diabetes.
G-Pen is a glucagon injection format studied in Xeris clinical trials, including NCT03091673 in pediatric type 1 diabetes patients and NCT02423980 for hypoglycemia rescue in type 1 diabetes. It refers to the same glucagon development program rather than a separate drug asset.