Phase 3 pharmacodynamics: blood pressure and heart rate versus intramuscular comparators

“AQST-109 demonstrated more rapid and larger increases in blood pressure and heart rate than the comparators.” (opens the source at this quote in a new tab)
“RD AQST-109 had greater than dose-proportional increases in PK and PD parameters, exceeding the comparators.” (opens the source at this quote in a new tab)

Integrated phase 1 pharmacodynamics: systolic and diastolic blood pressure and heart rate

“There was also an early, rapid, and consistent increase in systolic blood pressure, diastolic blood pressure, and heart rate after the administration of AQST-109.” (opens the source at this quote in a new tab)

Pivotal study: pharmacodynamic change at the first tracked time point

“Produced a meaningful change from baseline pharmacodynamic measures of blood pressure and heart rate at the first tracked time point of 2 minutes” (opens the source at this quote in a new tab)

Pharmacodynamic responses relative to auto-injectors and manual intramuscular epinephrine

“Importantly, Anaphylm has previously demonstrated a rapid onset together with robust increases in heart rate and blood pressure; these pharmacodynamic responses were comparable to or greater than those observed with auto-injectors and manual IM epinephrine in clinical studies.” (opens the source at this quote in a new tab)

Blood pressure direction compared with manual intramuscular injection

“Both SBP and DBP increased with the SL DESF and decreased after manual IM adrenaline.” (opens the source at this quote in a new tab)

Self-administration versus clinician administration: pharmacodynamic response

“Topline PD data from the study showed no difference in the median increase in systolic blood pressure, diastolic blood pressure, and heart rate whether Anaphylm was self-administered or HCP-administered.” (opens the source at this quote in a new tab)

Pharmacodynamics under oral allergen challenge

“Pharmacodynamics were not impacted by OAC after single- and repeat-dose administration of AQST-109 vs without OAC.” (opens the source at this quote in a new tab)
“Single- and repeat-dosing PD parameters were higher with AQST-109 after OAC vs intramuscular epinephrine injection without OAC, and were nonsignificantly higher for AQST-109 with vs without OAC.” (opens the source at this quote in a new tab)

Pharmacodynamics after deliberate top-of-tongue placement

“However, top-of-tongue placement resulted in a geometric mean Cmax above 100 pg/mL (baseline unadjusted), a median Tmax of 35 minutes, and clinically meaningful PD results that were comparable to or of greater magnitude than those observed with injectable epinephrine.” (opens the source at this quote in a new tab)

Pharmacodynamics after water of differing temperature and pH

“Topline PK and PD data from the study showed no statistically significant difference in PK and PD results between the different groups based on temperature and pH variability in the mouth.” (opens the source at this quote in a new tab)

Preclinical pharmacology: minipig exposure and prodrug half-life

“MiniPig data show similar exposure at lower doses” (opens the source at this quote in a new tab)

Preclinical pharmacology: adrenergic receptor potency of epinephrine and dipivefrin

Receptor and parameter	Epinephrine	Dipivefrin	Dipivefrin versus epinephrine ratio
Alpha-1 receptors, micromolar	“0.00018”	“0.41”	“2278”