Precision delivery device offers hope for menstrual migraine patients

The Office on Women’s Health—part of the US Department of Health and Human Service—reports that migraine pain and symptoms impact 29.5 million people. Of the female patients, nearly two-thirds suffer from migraine around the same time as their period—unfortunately, these migraines can be challenging to treat.

Impel Pharmaceuticals has received approval for Trudhesa (a prescription treatment indicated for acute treatment of migraine, with or without aura) in the US. Administered with the company's Precision Olfactory Device (POD), it can be used to treat menstrual migraine, targeting the upper nasal space to help enable faster absorption.

To learn more about the condition and the treatment-delivery combination, Outsourcing-Pharma connected with two experts:

• Lauren Natbony, medical director of Integrative Headache Medicine of New York; and assistant clinical professor of neurology, headache, and facial pain with the Icahn School of Medicine at Mount Sinai
• Sheena Aurora, vice president for medical affairs with Impel Pharmaceuticals

OSP: Dr. Natbony, please tell us a bit about yourself—your work at Icahn, how you came to focus on headache pain, and any accomplishments (yours and your team’s) you’re especially proud of.​

LN: I am the founder and medical director of Integrative Headache Medicine of New York, and assistant clinical professor of neurology in the division of Headache and Facial Pain at Mount Sinai’s Icahn School of Medicine. I previously served as the director of the Headache Medicine Fellowship at Mount Sinai and am actively involved in teaching headache fellows and neurology residents.

Headache medicine is both an art and a science. There is no one size fits all formula as each patient is unique. I am proud to have conceptualized and authored the book “Integrative Headache Medicine: An Evidence-Based Guide for Clinicians” as the foundational principles of my practice. A big part of my work focuses on educating and empowering patients by customizing treatment plans that address the physical, emotional, and social contributors to pain.

I am a frequent speaker at national headache conferences and enjoy educating healthcare professionals and the public on migraine and headache care. My work can be found in multiple textbooks and peer-reviewed journals, including Headache and Current Pain and Headache Reports. I can also be seen as a featured expert on the Today Show, Good Morning America, The Doctors TV, and more.

OSP: Could you please share some information about menstrual migraine—how is it similar to a general migraine attack, what makes it different, etc.?​

LN: Three times more women live with migraine than men and menstrual migraine (MM) affects a significant subset – about 20-25% – of females with the disease. MM is one of several types of migraine headaches. Other examples of migraine types include migraine with aura, migraine without aura, and chronic migraine.

MM can be divided even further into two types: attacks that occur only with menstruation and attacks that occur both during menstruation as well as during the rest of the cycle. While the most common symptoms of MM are similar to other forms – including a dull throbbing or severe pulsating headache, sensitivity to light, sound, nausea, and fatigue – MM is usually more severe, longer lasting, and tends to be more resistant to treatment due to the effects of hormones, particularly estrogen.

OSP: Then, what makes menstrual migraine challenging to treat?​

LN: Women with MM develop headaches anywhere from two days before to three days after the start of menstruation. It is believed that when estrogen levels rapidly drop before menstruation, there is an increased likelihood of developing a migraine attack. In fact, the fluctuating levels of estrogen, rather than the level itself, are believed to be the main trigger.

While estrogen plays a key role in MM pathogenesis, there are likely other contributing factors, including prostaglandin release and alterations in serum magnesium levels. Recent studies also show that estrogen seems to affect patients in different ways depending on their past medical history, age, and use of hormonal therapy.

OSP: Please share a bit about the journey that Trudhesa has taken from discovery to approval, and how it came to be recommended for treating menstrual migraines specifically.​

SA: Trudhesa (dihydroergotamine mesylate [DHE]) nasal spray (0.725 mg per spray) was approved in September of 2021 for the acute treatment of migraine with or without aura in adults. While not specifically approved to treat MM, the DHE molecule has been found to be helpful with difficult-to-treat migraine attacks such as rebound headaches, chronic daily headaches, and longer lasting migraine which is a typical symptom of MM. DHE has also been found to be effective in triptan non-responders.

Impel, founded in 2008, is the first company to investigate targeting delivery to the upper nasal space, initially by optimizing the pharmacokinetics of long-established therapeutic molecules, such as DHE. The company’s proprietary Precision Olfactory Delivery (POD) technology uses a unique approach to drug delivery that administers therapeutic molecules deep into the vascular-rich upper nasal space – a gateway for therapeutic administration of a versatile range of molecules and formulations. Trudhesa is Impel’s first commercially available product to use the POD technology.

OSP: What about the POD device makes it advantageous and beneficial for patients struggling with menstrual migraines?​

SA: The POD technology gives tough-to-deliver molecules, such as DHE, the “boost” they need to not only be more rapid and effective in providing symptomatic relief but also safe and easy to use outside of a hospital setting where it is traditionally administered by IV or intramuscular injection.

Relative to oral pill therapy competition, Trudhesa is also ideal for systemic drug delivery because it avoids first-pass metabolism by the liver and the gastrointestinal tract, thus avoiding a common phenomenon associated with migraine, which impacts the effectiveness of oral treatments, such as triptans.

OSP: Do you have anything to add?​

SA: There is a great deal of competition in this space, but we do believe Trudhesa has a unique value proposition that will help it emerge as a leader in the market: it is a proven drug with a new method of delivery that is less cumbersome on the physician and the patient. In the backdrop, Impel is also advancing its combination product candidate, INP105, an intranasal olanzapine product (a widely used atypical, second-generation antipsychotic) being developed as an acute treatment for agitation in persons with autism spectrum disorder via Impel’s POD technology.

The flexibility of Impel’s POD technology means that therapeutic possibilities are endless. The POD device can deliver both liquid and dry powder formulations of small and large therapeutic molecules, and the devices have components that can be altered based on the unique properties of the formulation and molecular structure to ensure accurate and consistent dosing. In studies of various compounds, the POD device has demonstrated the ability to deliver certain peptide and protein-based drugs that do not cross the blood-brain barrier on their own. This flexibility opens the door to a wide array of potential investigational programs across various disease states and scientific collaborations and partnerships.