Aquestive Therapeutics, a pharmaceutical firm headquartered in Warren, NJ, launched optimistic topline outcomes from its pivotal part 3 medical research of Anaphylm™, a sublingual movie positioned below the tongue to deal with extreme, life-threatening allergic reactions, together with anaphylaxis.
Anaphylm met all predefined major and secondary pharmacokinetic (PK) endpoints, attaining a time to most focus (Tmax) persistently sooner than conventional auto-injectors. After half-hour of dosing, publicity ranges have been similar to auto-injectors with no critical antagonistic results, and was well-tolerated.
The corporate acquired optimistic suggestions from the FDA throughout a current assembly and is on monitor to submit its new drug utility (NDA) earlier than the top of the yr.
Mentioned Daniel Barber, President and Chief Govt Officer of Aquestive:
We’re extraordinarily happy with the pivotal research outcomes in addition to our current FDA interplay. In the case of treating extreme allergic reactions together with anaphylaxis, we frequently hear from clinicians that fast absorption of epinephrine on the first signal of signs is crucial. Our pivotal research signifies that Anaphylm is similar to the main autoinjectors instantly following administration and our time to most focus, or Tmax, is quicker than the main autoinjectors. We consider this efficiency is unprecedented among the many alternate supply choices below improvement and are excited on the potential of Anaphylm as the one oral medication for therapy of extreme allergic reactions.
As well as, our current discussions with the FDA remained per our earlier interactions. We consider we now have a transparent understanding of the remaining medical improvement steps obligatory for a pre-NDA assembly with the FDA within the second half of the yr. Our aim continues to be to file our NDA earlier than the top of 2024 following completion of a optimistic pre-NDA assembly.
Mentioned David Golden, MD, an allergy-immunology advisor at Sinai Hospital of Baltimore and Franklin Sq. Hospital in Baltimore and an authority on anaphylaxis:
The information from the Anaphylm pivotal research construct on the compelling information generated from the prior Anaphylm pilot research. These newest research outcomes present that the sublingual administration of epinephrine supplies fast and sustained ranges of epinephrine much like authorized therapies. Anaphylm is a promising needle-free various to the present commonplace of care, permitting sufferers to simply carry and administer this life-saving treatment.
Topline Knowledge from Pivotal Section 3 Examine in Adults
The 2-part, Section 3, single-center, open-label, randomized research was designed to check the PK and pharmacodynamics (PD) of single and repeat doses of Anaphylm versus single and repeat doses of the epinephrine intra-muscular (IM) injection and epinephrine autoinjectors (EpiPen® and Auvi-Q®) in wholesome grownup topics. The first endpoint was to check the PK of epinephrine following the only administration of Anaphylm to the only administration of Adrenalin (epinephrine IM injection) and autoinjectors in wholesome grownup topics. The secondary endpoints included evaluating PK sustainability following repeat administration and the security and tolerability following single and repeat administrations versus epinephrine IM injection and epinephrine autoinjectors.
The one dose a part of the Section 3 research was designed as a four-period, four-treatment, four-sequence, comparative PK research with 64 enrolled grownup topics. As outlined within the presentation posted to the Firm’s web site and filed with the SEC at present, key findings from the only dosing a part of the research included that Anaphylm:
- Achieved a geometrical imply Cmax of 470 pg/mL bracketed by epinephrine autoinjectors AUVI-Q at 521 pg/mL and EpiPen at 469 pg/mL,
- Generated partial AUCs between (bracketed) autoinjectors and Adrenalin guide IM injection from 5 to 60 minutes
- Maintained a median Tmax of 12 minutes in comparison with 20 minutes for EpiPen, half-hour for AUVI-Q, and 50 minutes for Adrenalin,
- Produced a significant change from baseline pharmacodynamic measures of blood stress and coronary heart price on the first tracked time level of two minutes, and
- Was persistently effectively tolerated with no SAEs.
The repeat dosing a part of the Section 3 research was designed as a three-period, three-treatment, six sequence, comparative PK research with 36 enrolled grownup topics. As outlined within the presentation posted to the web site and filed with the SEC, the important thing findings from the repeat dosing a part of the Examine included that Anaphylm:
- Maintains epinephrine plasma concentrations equal to or larger than present injection merchandise in any respect however 1 timepoint out to 2 hours,
- Demonstrated a median Tmax of 10 minutes after administration of the second dose,
- Exhibited constant pharmacodynamics, and
- Was persistently effectively tolerated with no SAEs.
FDA Sort C Assembly
The Firm additionally efficiently accomplished a Sort C assembly with the FDA that addressed open gadgets from the November 2022 Finish-of-Section 2 assembly together with addressing (1) the affect of any product maintain time, (2) the potential for emesis (vomiting), and (3) the affect of potential mouth circumstances reminiscent of angioedema (swelling).
In response to those questions, the FDA indicated that the Firm has “adequately addressed” the FDA’s earlier considerations by eradicating product maintain time from the administration directions and offered further data on the way to characterize emesis within the Firm’s NDA submission.
Concerning mouth circumstances, the FDA advisable administering Anaphylm after oral publicity to a recognized allergen and assessing PK efficiency thereunder. The Firm will execute this research within the second quarter of 2024. This research will exchange the Firm’s beforehand deliberate angioedema research.
The FDA famous that substantial progress had been made within the Anaphylm medical improvement program and didn’t define any new medical improvement necessities. As anticipated, the FDA reiterated that, as with different epinephrine packages below improvement, concentrations of epinephrine above recognized EpiPen ranges should be justified from a security perspective, and PK sustainability stays a spotlight. Moreover, the FDA advisable that Aquestive start its pediatric research after completion of the remaining grownup research. The Firm is aligned with this advice from the FDA. The FDA reserved judgement on the sufficiency of the Anaphylm medical improvement program till completion of ongoing and deliberate research, the outcomes of that are anticipated to be offered on the pre-NDA assembly.
Desk 1 supplies an up to date view on the anticipated medical research dates.
Desk 1: Anaphylm Scientific Examine Timeline Standing
| Anticipated Timing |
Pivotal PK Research | Supportive PK Research | FDA Conferences / Actions |
| Accomplished | Section 3 PK Examine Repeat Dose PK Examine |
Sort C Assembly | |
| Q1 2024 | Temperature PK Examine | ||
| Q2 2024 | Self-administration PK Examine Allergen PK Examine |
||
| Q3 2024 | Pediatric PK Examine | ||
| H2 2024 | Pre-NDA Assembly |
The subsequent anticipated assembly with the FDA is the pre-NDA assembly focused for the second half of 2024. Aquestive’s aim is to file the NDA with the FDA earlier than yr finish 2024.
A presentation containing further details about this topline information and the Firm’s current FDA Sort C assembly is out there on the Occasions and Shows web page inside the Investor web page of the Aquestive web site.
About Anaphylm™
Anaphylm is a polymer matrix-based epinephrine prodrug candidate product. The product is analogous in dimension to a postage stamp, weighs lower than an oz, and begins to dissolve on contact. No water or swallowing is required for administration. The packaging for Anaphylm is thinner and smaller than a mean bank card, might be carried in a pocket, and is designed to face up to climate excursions reminiscent of publicity to rain and/or daylight. The tradename for AQST-109, “Anaphylm” has been conditionally authorized by the US Meals and Drug Administration (FDA). Ultimate approval of the Anaphylm proprietary title is conditioned on FDA approval of the product candidate.
