Trudhesa Difference

Trudhesa™ is the only migraine treatment that uses advanced Precision Olfactory Delivery (POD®) technology to consistently deliver dihydroergotamine mesylate (DHE) to the vascular-rich upper nasal space.2,4

Limitations of some oral acute treatments


Slow onset of action

Autonomic dysfunction is thought to be the shared pathophysiology of migraine and gut comorbidities. GI disorders can limit what oral medications can achieve by impacting drug absorption.1,5,6

Trudhesa circumvents GI issues by rapidly and consistently delivering DHE to the vascular-rich upper nasal space and into systemic circulation.2,4,7

Limitations of some oral acute treatments


Limited dosing windows

Many treatments for migraine need to be taken within 60 minutes of migraine attack onset to be most effective. But research shows patients often delay taking treatment for migraine symptoms.8,9*

Trudhesa can provide relief even when taken late into a migraine attack.10-13†

*In a US study of 338 patients with migraine, common reasons for delaying taking medication early were waiting to see if it was a migraine attack, only want to take medication for a severe attack, and concerns about side effects.9
Based on a phase 3, open-label safety study evaluating exploratory efficacy outcomes and post hoc analyses.13

Lack of consistency and sustained response

Migraine-associated GI issues may impact complete and consistent absorption of oral treatments.14 Studies of some oral treatments reported the incidence of recurrence varied from 6% to 50%.15,16 In separate studies, sustained pain freedom 24 hours postdose was achieved by about 16% of patients.17

Trudhesa provides consistent delivery of proven long-lasting DHE, for sustained relief time after time4,12,18

DHE for the treatment of migraine has a 70+ year history of proven effectiveness10,18,19


The efficacy of intravenous (IV) DHE is well-regarded
by physicians because of its:

  • Rapid onset and sustained effects lasting up to 48 hours10,21
  • Efficacy irrespective of the time of treatment—from within 2 hours to beyond 4 hours, post migraine attack onset10,21
  • Efficacy against a full range of migraine symptoms, including pain, allodynia, photophobia, and phonophobia11,21

Additional characteristics of DHE:

  • May prevent progression from peripheral to central sensitization11
  • Can potentially revers established central sensitization in patients treated later in migraine attacks10

Trudhesa delivered IV-like DHE levels13


Trudhesa reached maximum plasma concentration (Cmax) within 30 minutes2

IV-like levels sustained from 30 minutes to 48 hours2

All without the initial Cmax spike of IV DHE2

IV administration of DHE is associated with nausea.

  • Delivery of DHE via the upper nasal space has helped minimize this issue.13

Overcoming the limits of traditional nasal spray delivery4,10


TITLE: HOW DOES POD® TECHNOLOGY WORK?

VOICEOVER: The upper nasal space is a unique and underutilized environment for drug delivery. The ciliated olfactory epithelium in this richly vascularized space makes it ideal for rapid absorption into the systemic circulation, potentially leading to a faster response than oral medications. Potential benefits of delivery to this space also include the reduction of drug-related adverse effects and the potential avoidance of delayed absorption in the GI tract and first-pass metabolism in the liver.

Traditionally, nasal drug administration has focused on delivery to the lower nasal space, which is associated with significant drug loss from the nose with existing delivery systems, which may lead to variability in absorption. In addition, deep inspiration associated with existing systems can collapse the nasal valve essentially blocking access to the vascular rich upper nasal space.

Impel NeuroPharma’s POD technology is a hand-held, manually actuated, gas-propelled administration device uniquely designed to gently deliver drug to the upper nasal space without requiring breath control by the patient. With POD technology, the proprietary nozzle design allows for a narrow targeted plume of drug to effectively pass through the nasal valve to reach the rich vasculature and expansive surface area of the upper nasal space. The two-step action of the propellant launches the drug and then pushes it far into the upper nasal space.

This chart shows the increased delivery of radiolabeled tracer into the upper nasal space with POD technology compared with traditional nasal pump devices.

The mucosal layer in the upper nasal space tends to be more permeable and stable than the lower nasal cavity, permitting consistent, faster and more extensive absorption of drug into the underlying vasculature with less mucociliary clearance.

POD technology has the potential to provide rapid and consistent absorption of drug with total plasma exposure approaching that of intravenous administration from 20 minutes. Importantly, these consistent drug levels may result in a more reliable, clinical response.

The POD technology is a versatile platform technology that can be applied to both liquid and dry powder formulations. It can also be administered by either the patient or caregiver. Impel believes these benefits of POD technology have the potential to overcome the limitations of traditional nasal delivery systems.

POD technology—far from just a nasal spray4,10

POD is manually actuated and propellent powered so coordinated inhaling is not needed2,4,13

  • Prevents DHE from spilling down the front of the lip or down the throat to enable consistent drug delivery and possibly reduce adverse taste13
  • Avoids GI tract degradation and first-pass metabolism of oral treatments22
  • Circumvents the impact of autonomic dysfunction associated with migraine4,23
  • Gently and consistently delivers DHE into the upper nasal space2,4,12
  • Increased bioavailability compared to a traditional DHE nasal spray product13

There’s nasal,
and then there’s upper nasal2

The upper nasal space is highly permeable and vascular-rich, providing increased bioavailability by:

  • Rapid absorption into the bloodstream12
  • Consistent and predictable medication delivery13

Traditional Nasal Spray


POD Technology

Intranasal delivery demonstration

Safety

References: 1. Aurora SK, Shrewsbury SB, Ray S, Hindiyeh N, Nguyen L. A link between gastrointestinal disorders and migraine: insights into the gut-brain connection. Headache. 2021;61(4):576-589. 2. Shrewsbury SB, Jeleva M, Satterly KH, Lickliter J, Hoekman J. STOP 101: a phase 1, randomized, open-label, comparative bioavailability study of INP104, dihydroergotamine mesylate (DHE) administered intranasally by a I123 Precision Olfactory Delivery (POD®) Device, in healthy adult subjects. Headache. 2019;59(3):394-409. 3. Smith TR, Aurora S, Hocevar-Trnka J, Shrewsbury S. Acute treatment of migraine with INP104: exploratory efficacy from the phase 3 STOP 301 study. Poster presented at: American Headache Society Virtual Annual Scientific Meeting, June 3-6, 2021. 4. Trudhesa. Prescribing information. Impel NeuroPharma; 2021. 5. Lipton RB, Munjal S, Buse DC, et al. Unmet acute treatment needs from the 2017 Migraine in America Symptoms and Treatment Study. Headache. 2019;59(8):1310-1323. 6. Axert. Prescribing information. Janssen Pharmaceuticals; 2017. 7. Aurora SK, Papapetropoulos, Kori S. Gastric stasis in migraineurs: etiology, characteristics, and clinical and therapeutic implication. Cephalalgia. 2013;33(6):408-415. 8. Lantéri-Minet M, Mick G, Allaf B. Early dosing and efficacy of triptans in acute migraine treatment: the TEMPO study. Cephalalgia. 2012;32(3):226-235. 9. Foley KA, Cady R, Martin V, et al. Treating early versus treating mild: timing of migraine prescription medications among patients with diagnosed migraine. Headache. 2005;45(5):538-545. 10. Silberstein SD, Shrewsbury SB, Hoekman J. Dihydroergotamine (DHE) – then and now: a narrative review. Headache. 2020;60(1):40-57. 11. Aurora SK, Ray S, Satterly K, Shrewsbury SB, Hoekman J. Does dihydroergotamine treat the “whole migraine”? Poster presented at: American Headache Society Virtual Annual Scientific Meeting, June 2020. 12. Data on File. Impel NeuroPharma. 2020. 13. Smith TR, Winner P, Aurora SK, Jeleva M, Hocevar-Trnka J, Shrewsbury SB. STOP 301: a phase 3, open-label study of safety, tolerability, and exploratory efficacy of INP104, Precision Olfactory Delivery (POD®) of dihydroergotamine mesylate, over 24/52 weeks in acute treatment of migraine attacks in adult patients [published online ahead of print, 2021 Aug 7]. Headache. 2021;10.1111/head.14184. doi:10.1111/head.14184. 14. Láinez MJ, García-Casado A, Gascón F. Optimal management of severe nausea and vomiting in migraine: improving patient outcomes. Patient Relat Outcome Meas. 2013;4:61-73. 15. Dodick DW, Lipton RB, Ailani J, et al. Ubrogepant for the treatment of migraine. N Engl J Med. 2019;381(23):2230-2241. 16. Croop R, Goadsby PJ, Stock DA, et al. Efficacy, safety, and tolerability of rimegepant orally disintegrating tablet for the acute treatment of migraine: a randomised, phase 3, double-blind, placebo-controlled trial. Lancet. 2019;394(10200):737-745. 17. Diener HC, Tassorelli C, Dodick DW, et al; International Headache Society Clinical Trials Standing Committee. Guidelines of the International Headache Society for controlled trials of acute treatment of migraine attacks in adults: Fourth edition. Cephalalgia. 2019;39(6):687-710. 18. Tepper SJ, Ailani J, Shrewsbury SB, Aurora SK. Recurrence rates for INP104 for the acute treatment of migraine: results from the phase 3 STOP 301 study. Poster presented at: American Headache Society Virtual Annual Scientific Meeting, June 3-6, 2021. 19. US Food and Drug Administration. [email protected]: FDA-Approved Drugs. https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm. Accessed August 24, 2021. 20. Saper JR, Silberstein S, Dodick D, Rapoport A. DHE in the pharmacotherapy of migraine: potential for a larger role. Headache. 2006;46(suppl 4):S212-S220. 21. Aurora SK, Ray S, Satterly K. DHE pharmacology revisited: does a broad receptor profile molecule treat the whole migraine? Poster presented at: American Headache Society Virtual Annual Scientific Meeting, June 2020. 22. Hoekman J, Ray S, Aurora SK, Shrewsbury SB. The upper nasal space—a novel delivery route ideal for central nervous system drugs. US Neurology. 2020;16(1):25-31. 23. Aurora SK, Papapetropoulos, Kori S. Gastric stasis in migraineurs: etiology, characteristics, and clinical and therapeutic implication. Cephalalgia. 2013;33(6):408-415.