Impel NeuroPharma Announces US FDA Approval of TRUDHESA Nasal Spray for the Acute Treatment of Migraine

Impel NeuroPharma, Inc. recently announced the US FDA approved TRUDHESA (dihydroergotamine mesylate) nasal spray (0.725 mg per spray) for the acute treatment of migraine with or without aura in adults. TRUDHESA was previously known as INP104.

Using Impel’s proprietary Precision Olfactory Delivery (POD) technology, TRUDHESA gently delivers dihydroergotamine mesylate (DHE)—a proven, well-established therapeutic—quickly to the bloodstream through the vascular-rich upper nasal space. TRUDHESA bypasses the gut and potential absorption issues, offering rapid, sustained, and consistent symptom relief without injection or infusion, even when administered hours after the onset of a migraine attack. The Commercial launch of TRUDHESA is planned for early October 2021.

“We are delighted with the approval of TRUDHESA and are proud to offer the millions of Americans with migraine a non-oral, acute treatment option that may provide rapid, sustained, and consistent relief, even when taken late into a migraine attack,” said Adrian Adams, Chairman and Chief Executive Officer of Impel NeuroPharma. “The approval of TRUDHESA marks the culmination of more than a decade of research and advanced engineering to pair the proven efficacy of DHE with our innovative POD technology. We are grateful for all the patients and investigators who participated in our clinical trials and who were instrumental in bringing this needed advancement to the migraine community.”

The New Drug Application for TRUDHESA included the results of the Phase 3, open-label, pivotal safety study, STOP 301, which is the largest longitudinal study ever conducted with DHE using nasal spray delivery. More than 5,650 migraine attacks were treated over 24 or 52 weeks during the study. The primary objective of the study was to assess the safety and tolerability of TRUDHESA. Exploratory objectives included efficacy assessments of migraine measures and a patient acceptability questionnaire. In the trial, TRUDHESA was generally well tolerated and exploratory efficacy findings showed it provided rapid, sustained, and consistent symptom relief. Unlike some oral acute treatments that need to be taken within one hour of attack onset to be most effective, STOP 301 reported TRUDHESA offered consistent efficacy even when taken late into a migraine attack.

“Many of my patients need more from their migraine treatment, and TRUDHESA offers a non-oral, fast-acting, reliable option that overcomes many current medication challenges,” said Stephanie J. Nahas-Geiger, MD, MSEd, Associate Professor in the Department of Neurology, and Program Director of the Headache Medicine Fellowship Program, Thomas Jefferson University. “Its upper nasal delivery circumvents the GI tract and common phenomena associated with migraine, such as nausea and gastroparesis, that can impact the effectiveness of oral treatments. And, importantly, it is a self-administered, single dose that can be taken anytime during a migraine attack, so patients don’t need to worry about missing the opportunity to benefit from using TRUDHESA within a certain timeframe. I think patients will be very receptive to this treatment, because it pairs the long-proven benefits of DHE with a patient-friendly delivery system.”

There were no serious TRUDHESA-related treatment-emergent adverse events (TEAEs) observed in the STOP 301 study and the majority of TEAEs were mild and transient in nature.⁴ Some of the most frequently reported TRUDHESA-related TEAEs (≥2%) during the entire 52-week study period were nasal congestion (17.8%), nausea (6.8%), nasal discomfort (6.8%), abnormal olfactory test (6.8%) and vomiting (2.7%).

In the STOP 301 study, patient-reported exploratory efficacy findings reported that more than a third of patients (38%) had pain freedom, two-thirds (66%) had pain relief, and more than half (52%) had freedom from their most bothersome migraine symptom at two hours after their first dose of TRUDHESA. For one in six patients (16%), pain relief started as early as 15 minutes. Of patients who were pain free at two hours, 93% were still pain free at 24 hours, and 86% were still pain free through two days. The great majority of patients (84%) reported that TRUDHESA was easy to use and preferred it over their current therapy.

“Migraine is a disease that impacts the whole body and is the second leading cause of disability,” said Kevin Lenaburg, Executive Director, Coalition for Headache and Migraine Patients (CHAMP), which represents 12 national headache and migraine patient advocacy groups. “Historically there have not been enough effective treatments for treating migraine attacks, especially treatments that are not oral medicines, which can be challenging due to nausea, vomiting and other GI symptoms that can occur during a migraine. We welcome an important new treatment that combines the long-established efficacy of DHE with a non-oral, innovative delivery system that allows patients to self-administer wherever they are and at any point within a migraine attack.”

TRUDHESA will be available through Trudhesa Direct, a hassle-free pharmacy partnership and copay program. The digital pharmacy fulfilment partners, Phil Inc. and Carepoint Pharmacy, will provide electronic prescribing and automatic enrollment in the patient savings program for eligible, commercially insured patients without the need for a paper copay card. The pharmacy partners will provide a customized and seamless patient experience. Once the pharmacy receives the e-prescription, patients will be notified via digital communications that their prescription has been processed and receive their medication via convenient, free, home delivery. For more information, please visit, www.TRUDHESA.com.

Approximately 31 million adults in the US are living with migraine, which is characterized by recurrent episodes of moderate to severe head pain and associated with nausea, vomiting and sensitivity to light and sound. Migraine is the second most common cause of disability in the world and the most common cause of disability among young women.

In a 2017 survey of nearly 4,000 US patients using oral acute prescription medication for migraine, 96% said they were dissatisfied with at least one aspect of their treatment—including lack of sustained relief, inconsistent relief, and lack of relief from a rapid-onset attack. Nearly half (48%) said they can still have pain two hours after taking medication and 38% say their headache returns within 24 hours of getting relief.

The high prevalence of related GI conditions among people with migraine may require alternative routes of medication delivery. Evide0ce suggests 80% of people with migraine experience gastroparesis, delayed emptying of the stomach, which may delay or reduce the absorption of oral medications. Additionally, more than 70% of people with migraine experience nausea and nearly 30% experience vomiting. The American Headache Society guidelines recommend a non-oral therapy for patients who have limited or no response to oral medicine.

TRUDHESA (dihydroergotamine mesylate) nasal spray (0.725 mg per spray) is approved by the US FDA for the acute treatment of migraine with or without aura in adults in the US. Using Impel’s proprietary Precision Olfactory Delivery (POD) Technology, TRUDHESA gently delivers dihydroergotamine mesylate (DHE)—a proven, well-established therapeutic—quickly to the bloodstream through the vascular-rich upper nasal space. TRUDHESA bypasses the gut and potential absorption issues, offering the potential for rapid, sustained, and consistent relief without injection or infusion, even when administered hours after the start of a migraine attack.

TRUDHESA is a single use, drug-device combination product containing a vial of DHE (4 mg DHE in a 1 mL solution that is clear and colorless to faintly yellow) and a POD device. Prior to initiation of TRUDHESA, a cardiovascular evaluation is recommended. For patients with risk factors predictive of coronary artery disease who are determined to have a satisfactory cardiovascular evaluation, it is strongly recommended that administration of the first dose of TRUDHESA take place in the setting of an appropriately equipped healthcare facility.

TRUDHESA is designed to be self-administered. Once assembled, TRUDHESA should be primed before initial use by releasing 4 sprays. A patient should use TRUDHESA immediately after priming. The recommended dose of TRUDHESA is 1.45 mg administered as two metered sprays into the nose (one spray of 0.725 mg into each nostril). The dose may be repeated, if needed, a minimum of 1 hour after the first dose. A patient should not use more than 2 doses of TRUDHESA within a 24-hour period or 3 doses within a 7-day period. A patient should use or discard TRUDHESA within 8 hours once the vial has been opened or the product has been assembled. A consumer assembly video is available on www.TRUDHESA.com.

The most common adverse reactions (incidence ≥2%) to TRUDHESA were nasal congestion, nasal discomfort, nausea, product taste abnormal, and product package associated injury. For more information about TRUDHESA and Full Prescribing Information, including BOXED WARNING, please visit, www.TRUDHESA.com.

Impel NeuroPharma, Inc. is a commercial-stage biopharmaceutical company developing transformative therapies for people suffering from diseases with high unmet medical needs, with an initial focus on diseases of the central nervous system. Impel offers and is developing treatments that pair its proprietary Precision Olfactory Delivery (POD) technology with well-established therapeutics. In addition to TRUDHESA (dihydroergotamine mesylate) nasal spray, which is approved in the United States for the acute treatment of migraine with or without aura in adults, impel is also developing INP105 for the acute treatment of agitation and aggression in patients with autism, and INP107 for OFF episodes in Parkinson’s disease.