Anaphylm (dibutepinephrine)

“Achieved a geometric mean Cmax of 470 pg/mL bracketed by epinephrine autoinjectors AUVI-Q at 521 pg/mL and EpiPen at 469 pg/mL” (opens the source at this quote in a new tab)CopyFlag

“Generated partial AUCs between (bracketed) autoinjectors and Adrenalin manual IM injection from 5 to 60 minutes” (opens the source at this quote in a new tab)CopyFlag

“Maintained a median Tmax of 12 minutes compared to 20 minutes for EpiPen, 30 minutes for AUVI-Q, and 50 minutes for Adrenalin” (opens the source at this quote in a new tab)CopyFlag

“After single dose AQST-109 administration, area under the curve and maximum serum concentration met the primary end point of PK bracketing of 60 minutes, exceeding that of manual intramuscular injection, equaling EpiPen, but lower than that of Auvi-Q.” (opens the source at this quote in a new tab)CopyFlag

“AQST-109 had a median time-to-maximum plasma concentration of 12 minutes, exceeding that of EpiPen (20 minutes), Auvi-Q (30 minutes), and intramuscular injection (50 minutes); there was also more consistency (narrower IQR) than the comparators.” (opens the source at this quote in a new tab)CopyFlag

“Single dose AQST-109 demonstrated PK exposures consistently bracketed within established levels for approved intramuscular epinephrine and autoinjectors, with a more rapid time-to-maximum plasma concentration and comparable PD responses.” (opens the source at this quote in a new tab)CopyFlag

“Maintains epinephrine plasma concentrations equal to or greater than existing injection products at all but 1 timepoint out to 2 hours” (opens the source at this quote in a new tab)CopyFlag

“Demonstrated a median Tmax of 10 minutes after administration of the second dose” (opens the source at this quote in a new tab)CopyFlag

“AQST-109 yielded comparable epinephrine PK and exposure to both manual intramuscular injections and epinephrine autoinjectors.” (opens the source at this quote in a new tab)CopyFlag

“The median time to maximum concentration (Tmax) for AQST-109 was 15 minutes, compared with EpiPen (10 minutes), generic EpiPen (15 minutes), Auvi-Q (30 minutes), and manual intramuscular injection (50 minutes).” (opens the source at this quote in a new tab)CopyFlag

“AQST-109 delivered epinephrine with PK and PD results within the bracketed range of approved intramuscular products.” (opens the source at this quote in a new tab)CopyFlag

“The twenty - four subjects returned to receive single ascending SL doses up to 24 mg in a sequential fashion .” (opens the source at this quote in a new tab)CopyFlag

“Formulation 2 met the predefined stopping criteria after the 12 mg dose . Formulation 1 met the stopping criteria after the 18 mg dose .” (opens the source at this quote in a new tab)CopyFlag

“AQST - 109 SL film demonstrated consistent Tmax values in a tighter range than reported for injectable epinephrine.” (opens the source at this quote in a new tab)CopyFlag

“In addition, using the revised packaging and revised instructions for use, the Company conducted a single PK study in healthy volunteers comparing self-administration to clinician-administered as well as manual intramuscular (IM) administration. No administration errors were observed in the self-administration arm of the PK study.” (opens the source at this quote in a new tab)CopyFlag

“The median time to maximum concentration (Tmax) was 15 minutes for both the Anaphylm self-administered and HCP-administered arms, while the median Tmax for the Adrenalin IM HCP administered arm was 50 minutes post administration.” (opens the source at this quote in a new tab)CopyFlag

“There was no statistical difference between the Anaphylm self- administered and HCP-administered arms of the study.” (opens the source at this quote in a new tab)CopyFlag

“The data showed that administering the film sublingually two minutes after consuming a peanut butter sandwich had no statistical impact on the resulting pharmacokinetics when compared to previous data from the initial Part 3 dataset. The medium time to maximum concentration (Tmax) and partial area under the curve (AUC) results were comparable and the time to reach Tmax remained 12 minutes when sublingually administered after consumption of a peanut butter sandwich. The geometric mean maximum concentration, or Cmax of 286 pg/mL was also comparable to previous data from Part 3.” (opens the source at this quote in a new tab)CopyFlag

“The data also showed that swallowing the film whole immediately with water unexpectedly resulted in significant absorption of epinephrine.” (opens the source at this quote in a new tab)CopyFlag

“The Cmax was 313 pg/mL and the Tmax, while slower than the sublingual administration was significantly faster than the epinephrine 0.3mg IM injection from Parts 1 and 2 of the EPIPHAST study.” (opens the source at this quote in a new tab)CopyFlag

“The single-dose, five-period, randomized crossover study was designed to compare the PK and PD of Anaphylm just after consuming normal water at different temperatures (hot, cold, and room temperature) as well as water of different pHs (acidic- lemon water, and basic- baking soda water).” (opens the source at this quote in a new tab)CopyFlag

“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)CopyFlag

“The analysis showed that 87.5% of subjects maintained consistent film placement during disintegration. In the 12.5% of subjects where movement was noted, there were no significant differences in Cmax and Tmax. These findings further demonstrate that initial placement or subsequent movement of the sublingual film had no impact on epinephrine PK or PD comparability to epinephrine autoinjectors.” (opens the source at this quote in a new tab)CopyFlag

“The FDA also requested that Aquestive include a PK arm studying purposely misplaced administration of Anaphylm on top of the tongue or on the roof of the mouth, intended to demonstrate the impact of incorrect placement on PK and PD measures and tolerability. As expected, compared with prior clinical studies where the film was administered as per the instructions, the geometric mean Cmax is significantly lower and the Tmax significantly longer than with correct placement of our sublingual film.” (opens the source at this quote in a new tab)CopyFlag

“Furthermore, the PK‐PD data were compared according to three different methods of administration in 24 healthy adult volunteers: keeping the film 4 min under the tongue before swallowing saliva, 2 min under the tongue before swallowing saliva and keeping the film under the tongue while swallowing saliva at the same time. The data were similar in the three situations without a benefit for keeping the film beyond 2 min [55].” (opens the source at this quote in a new tab)CopyFlag

“During screening with OAC, 94.4% of the 36 patients experienced moderate or severe oral symptoms.” (opens the source at this quote in a new tab)CopyFlag

“AQST-109 PK values were similar with or without OAC.” (opens the source at this quote in a new tab)CopyFlag

“AQST-109 PK and PD are not diminished with oral symptoms and changes, supporting reliable absorption in allergic reactions in such contexts.” (opens the source at this quote in a new tab)CopyFlag

“The two-part study demonstrated that Anaphylm's PK and PD profile during allergen-induced oral physiological changes was consistent with its profile without an allergen challenge.” (opens the source at this quote in a new tab)CopyFlag

“The PK profile remained consistent, with median Tmax maintained at 12 minutes and comparable Cmax values between allergen-exposed and non-exposed cohorts.” (opens the source at this quote in a new tab)CopyFlag

“These results demonstrate that Anaphylm maintains its consistent PK profile in pediatric patients between the ages of seven and seventeen and weighing greater than thirty kilograms.” (opens the source at this quote in a new tab)CopyFlag

“A total of thirty-two patients completed the study. The PK results were consistent with previous adult studies.” (opens the source at this quote in a new tab)CopyFlag

“Data from these studies indicate promising pharmacokinetic results comparable to those of the standard of outpatient emergency care (0.3-mg EAI) and syringe and needle IM epinephrine administration. Several products have shown maximum plasma concentration values higher than those of the 0.3-mg EAI and manual IM injection, although it remains unclear whether this has clinical relevancy in patient outcomes. Generally, these modalities show comparable time to maximum concentrations.” (opens the source at this quote in a new tab)CopyFlag