Regulatory Decision Summary for Baqsimi

This NDS was filed to obtain marketing authorization for Baqsimi, a ready-to-use nasal powder that delivers 3 mg of glucagon in a single-use intranasal dispenser to treat severe hypoglycemia in adults and children with diabetes. Notably, the product does not require reconstitution before injection or refrigeration, and patients do not need to inhale or breathe deeply after dosing, enabling drug delivery even in unconscious patients.

The safety and efficacy of Baqsimi was assessed in two randomized clinical studies (IGBC and IGBI) in adult patients with Type 1 (T1D) and type 2 diabetes (T2D) and in one clinical study in children and adolescents with T1D (IGBB). To supplement the clinical data generated in controlled clinical settings, 2 actual-use studies, one in adults, one in children, were conducted to evaluate the clinical response of patients in the event of hypoglycemia during real-world diabetes management.

The main pivotal study in adults, study IGBC was a randomized, multicenter, open-label, 2-period, crossover study, which compared the efficacy and safety of 3 mg NG to 1 mg of intramuscular glucagon (IMG) in reversing insulin-induced hypoglycemia in patients with T1D or T2D. This study enrolled 83 patients who were the majority of them were diagnosed with T1D. In this study, insulin was used to reduce blood glucose levels to the hypoglycemic range with a target blood glucose nadir of <2.8 mmol/L. The primary efficacy outcome was the proportion of patients achieving treatment success, which was defined as either an increase in blood glucose to ≥3.9 mmol/L or an increase of ≥1.1 mmol/L from glucose nadir within 30 minutes after receiving glucagon. The primary analysis population was patients with T1D. The proportions of T1D patients who achieved treatment success was 98.7% (n = 74) in the NG group and 100% in the IMG treatment group. Baqsimi demonstrated non-inferiority to IMG in reversing insulin-induced hypoglycemia and only one patient receiving NG failed treatment at 30 minutes but achieved both glucose threshold levels at 40 minutes post dosing. The mean time to treatment success, which did not include glucagon preparation time, was 16.2 and 12.2 minutes in the NG 3 mg and IMG 1 mg treatment groups, respectively. All patients with T2D achieved treatment success within 30 minutes of glucagon dosing.

Study IGBI was a randomized, multicenter, open-label, 2-period, crossover study in adult patients with T1D, conducted with the commercial drug product. Study IGBI mimicked the design of study IGBC and used the same injectable glucagon comparator, thus allowing an indirect comparison between the commercial and clinical trial drug products. Seventy patients with T1D were enrolled, with a mean age of 42 years and a mean diabetes duration of almost 20 years. All patients (100%) in each treatment group achieved treatment success. The results of Study IGBI demonstrated clinical comparability to Study IGBC, which allows reliance on data previously generated with the clinical trial drug product.

In the pivotal pediatric study (Study IGBB) in patients (4-<17 years of age, n = 48) with T1D, 100% of the patients achieved treatment success; an increase in glucose of ≥1.1 mmol/L from glucose nadir within 20 minutes after the administration of NG 3 mg or IMG (0.5 mg or 1 mg based on weight). In all age-subgroups, the glucose responses were comparable between the NG 3 mg and the IMG.

A similar benefit was observed in the actual-use studies, which evaluated the effectiveness of NG in response to moderate or severe hypoglycemic events in a real-world setting.

The safety profile of NG was assessed in 9 clinical studies in adult patients with and without diabetes (n = 461), and in 2 studies in pediatric patients (4 to <18 years of age) with diabetes mellitus (n = 60). The safety database for NG is considered sufficient and adequately characterized the safety profile of NG in adult and pediatric patients given the history of safe use with the currently approved injectable glucagon products. The most commonly reported treatment-emergent adverse events (TEAEs) following NG treatment, in both adult and pediatric populations, were local tolerability effects consistent with the nasal route of administration (headache or upper respiratory tract irritation) and other well known effects of glucagon treatment (nausea and vomiting). In general, these events were mild to moderate in severity, transient in nature and infrequently led to discontinuation. The rates of occurrence of nausea and vomiting were similar between treatments. There were no reports of deaths or serious adverse events. In the NG program, non-clinically significant changes in blood pressure and heart rate were observed.

Baqsimi provides a well-tolerated treatment with clinically and statistically significant glycemic benefits. The product reduces treatment complexity that in turn may improve the delivery of treatment for the serious condition of severe hypoglycemia in patients with diabetes. All safety concerns and uncertainties were adequately addressed in the Canadian Product Monograph (PM).

Based on the totality of the data, Baqsimi has a positive benefit-risk-uncertainty profile for the treatment of severe hypoglycemic reactions, which may occur in the management of insulin-treated adult and pediatric patients with diabetes mellitus, when impaired consciousness precludes oral carbohydrates.