Pharmacokinetics and Pharmacodynamics of Neffy (1 Mg) Compared to EpiPen (0.3 Mg) and Manual IM Injection (0.3 Mg) – an Integrated Analysis

ARS Pharmaceuticals Inc. (ARS) is investigating a 1 mg intranasal (IN) epinephrine spray (Neffy) for the treatment of anaphylaxis in pediatric patients as safer and more convenient alternative to epinephrine autoinjectors. An integrated analysis of Neffy (1 mg IN), EpiPen (0.3 mg), and manual IM injection (0.3 mg) was conducted using data from multiple randomized crossover Phase I clinical studies examining pharmacokinetics and pharmacodynamics in healthy adult subjects. Pharmacokinetics: One hundred and seventy-one subjects were included. Geometric mean maximum plasma concentration (Cmax) values were highest following EpiPen (483 pg/mL) and lower for both Neffy (222 pg/mL) and manual IM administration (272 pg/mL). Median time to maximum plasma concentration (tmax) values were shortest following EpiPen administration (12 minutes), followed by Neffy (20 minutes) and manual IM administration (45.0 minutes). Pharmacodynamics: Both Neffy and EpiPen improved pharmacodynamic responses (systolic blood pressure [SBP], diastolic blood pressure [DBP], and pulse rate [PR]) relative to IM injection. The mean maximum SBP response (Emax) was16.7 mmHg following Neffy and 17.0 mmHg following EpiPen. In contrast, the mean SPB Emax following manual IM injection was 10.0 mmHg. The mean DBP Emax was greatest for Neffy (8.5 mmHg), followed by EpiPen (5.9 mmHg) and manual IM injection (3.4 mmHg). Similarly, the mean HR Emax was 14.5 and 16.3 bpm following Neffy and EpiPen, respectively and 12.8 bpm following IM injection. Neffy 1mg demonstrated a PK profile lower than approved injection products but resulted in comparable PD responses, possibly translating into similar hemodynamic effects.