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Migraine patients have regularly complained about treatments not providing enough pain relief and the recurrence of headaches. Pharmaceutical Executive spoke with Adrian Adams, chairman and chief executive officer of Impel Pharmaceuticals, about how his company developed a new medicine designed to meet patients’ needs.
Pharm Exec: What are the greatest issues in the development of new therapies for migraines today?
Adams: The migraine market is large and growing but, despite this, there remains significant unmet need with multifactorial patients. While treatment options have increased substantially in the past few years, many shortcomings remain—including efficacy, speed of onset to pain relief, tolerability, ease of use, and method of delivery.
In a 2017 US survey of nearly 4,000 people using oral acute prescription medications for migraine, 96% said they were dissatisfied with at least one aspect of their treatment, from lack of sustained relief to inconsistent relief, to lack of relief from a rapid-onset attack. Common areas of unmet need included inadequate two‐hour pain freedom (49%) and headache recurrence within 24 hours (38%).
The high prevalence of related gastrointestinal (GI) conditions among people with migraine suggests the need for alternative routes of medication delivery. Evidence reveals that 80% of people with migraines experience gastroparesis (delayed emptying of the stomach), 73% experience nausea, and 29% experience vomiting. Further, the American Headache Society guidelines recommend a non-oral therapy for the many patients who have limited or no response to oral medicine.
Pharm Exec: Why hasn’t there been much progress in the migraine space over the years?
Adams: The migraine treatment space had not seen a great deal of innovation in several decades until the arrival of the calcitonin gene-related peptide (CGRP) inhibitors, and certainly not in new delivery approaches for the treatment of acute migraine that can help patients quickly and safely achieve relief compared to their previous regimens. While anti-CGRPs have changed the migraine treatment landscape, many feel that they fall short of delivering complete relief, leaving a potential opening for Trudhesa, a nasal spray for migraine. It is of note that over 60% of patients who are placed on the newer gepants [first- and second-generation CGRP receptor antagonists] either drop off therapy or are switched to another therapy—predominantly due to efficacy concerns.
Clearly the migraine treatment landscape—both for acute and preventive treatment—has benefited from an increased understanding of disease pathophysiological factors such as the central and peripheral neural pathways, neuropeptides, and neurotransmitters.
But even with the emergence of therapeutics incorporating new mechanisms of action, such as 5-HT1F receptor agonists and CGRP antagonists, doctors are still challenged in many cases to find the right medications for their patients.
Pharm Exec: How important is patient engagement and patient centricity in creating migraine therapies?
Adams: Trials for migraine are more patient-centric than ever before. In 2018, the FDA updated the acute treatment guidelines to require pain freedom and freedom from the most bothersome symptoms (MBS), for which each patient self-identifies among light- and sound-discomfort, or nausea. By tracking MBS in clinical trials, Impel can determine which symptoms respond to which drug classes. This helps us to better equip physicians with more effective ways of treating migraine sufferers according to how migraine impacts them at an individual level, in addition to alleviating their migraine pain.
The migraine treatment landscape is as diverse and complex as the many ways the disease presents in people. The severity, frequency, and characteristics of migraine vary among patients, and often within individuals over time. There is still no means of identifying symptom profiles or biomarkers that could help doctors predict efficacy and side effects at the individual level. So along with MBS, the industry needs to conduct more qualitative research to learn about the patient’s perspective and satisfaction with treatment. Collectively, we need to involve patients and caregivers when developing treatment plans to help ensure adoption and set expectations.
Pharm Exec:Could you discuss your product strategy, which is founded on leveraging established therapeutics for new indications?
Adams: Since its 2008 inception, Impel Pharmaceuticals (formerly known as Impel NeuroPharma) was founded on the premise that the upper nasal space can provide an optimal treatment entry point for central nervous system (CNS) and many other diseases where rapid vascular absorption can result in superior clinical outcomes in terms of efficacy, consistency, and reliability. It was recognized that no device existed that deposited drugs consistently and predictably to the vascular-rich upper nasal space.
This observation led to the development and commercialization of the company’s proprietary Precision Olfactory Delivery (POD®) technology. This technology can deliver both liquid and dry powder formulations and is not limited to existing medications. Additionally, the technology enables for components that can be altered based on the unique properties of the formulation and molecular structure to ensure an accurate and consistent dosing.
Our product development strategy for Trudhesa has leveraged the therapeutic dihydroergotamine mesylate (DHE) administered via the POD. DHE is another example of existing drugs that are repurposed—either by finding new targets, delivery methods, or formulations—that will make a real impact on care.
DHE is unique among other available migraine therapeutics due to its ability to bind to multiple receptors implicated in migraine onset and duration. It is recognized as being a gold standard efficacy treatment, but its prior use had been limited because of the inability to deliver this in a predictable and patient-friendly way. These limitations were also related to the delivery of DHE via intravenous and intramuscular routes, which for many patients are not the preferred route for any medication. Unlike traditional nasal sprays, Trudhesa delivers DHE via the POD technology to the upper nasal space, bypassing the gut and with an improved tolerability and consistent efficacy profile.
The performance of Trudhesa to date affirms that our approach has been well-received among prescribers and patients—exceeding our expectations, with a strong trajectory of new and repeat prescriptions. Importantly, we have also secured broad and favorable Trudhesa contracts and payer coverage with several leading pharmacy benefit managers, which together cover approximately 80% of US commercial lives.
Pharm Exec: What has been your commercialization strategy with Trudhesa, given the competitive environment?
Adams: The company was incredibly pleased to complete a successful initial public offering (IPO) in April 2021. This, together with additional financing initiatives, has enabled Impel to raise over $250 million for commercialization and ongoing R&D efforts. Pursuant to the September 2021 FDA approval of Trudhesa, we began commercialization of the product utilizing a highly targeted strategy with a 60-person highly qualified salesforce targeted to 8,000 physicians made up predominantly of neurologists and high-prescribing primary care physicians. This together with our strong managed-care position and excellent medical affairs team have enabled a strong launch to date.
Pharm Exec: What other therapeutic areas could Impel’s nasal delivery platform be used for?
Adams: Impel continues to advance its pipeline with its next 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. Since filing the investigational new drug application in November 2021, Impel has been working with the FDA to finalize the Phase IIa proof-of-concept clinical protocol and anticipates the study will start in H1 2022 with a data readout anticipated in H1 2023.
Knowing that Trudhesa and our POD technology is benefitting the lives of many patients, in a remarkably busy marketplace with numerous competitors, indicates a great start for a promising therapeutic and delivery device, and our company.
As mentioned, when Impel was founded, it recognized that the POD technology and its unique delivery to the upper nasal space has broad utility across multiple disease states. This is also illustrated by the inbound levels of interest we have had from small and large pharma companies interested in partnering with Impel for our POD technology. This corporate and business development landscape represents an exciting and transformational opportunity for our company. This also played a part in the recent change of name from Impel NeuroPharma to Impel Pharmaceuticals. This is exciting for the company, its employees, our shareholders, and the healthcare providers and patients we serve.