Impel NeuroPharma presented positive results from the open-label, Phase III STOP 301 study of its novel intranasal migraine candidate, INP104 (dihydroergotamine [DHE ] mesylate), at the virtual 2021 American Academy of Neurology (AAN) conference held on 17-22 April.

The STOP 301 study evaluated safety and efficacy outcomes in 354 patients, who were asked to complete a daily diary over a period of 24 and 52 weeks of the self-administered intermittent use of INP104 in treating their migraine attacks. The study demonstrated that INP104 improved pain freedom at two hours in 38% of patients versus 26% of patients on their best usual care, which included many oral classes such as triptans and non-steroidal anti-inflammatory drugs. It also showed that pain relief occurred as early as 15 minutes after treatment in some patients. The drug was well tolerated in the majority of patients and only showed minor side effects. The predominant side effect was nasal congestion, which is not uncommon with this delivery route.

Following these results, the US Food and Drug Administration (FDA) is anticipated to make a decision on the drug’s filing by September. If approved, GlobalData believes that INP104 has the potential to fit into the crowded acute migraine treatment armamentarium due to the benefits of its novel delivery system. It will likely have a small share, however, due to heavy competition from other drug classes, including triptans and monoclonal antibodies. GlobalData forecasts the global migraine market to reach $8.7bn in sales by 2026.

INP104 belongs to the DHE class of drugs, a highly potent and long-established therapeutic class within the migraine space. This class is preferred for patients with cardiovascular problems, as it is not attributable to cerebral vasoconstriction compared to triptans. INP104 is delivered intranasally through a novel device called a precision olfactory delivery (POD). This device aims to deliver the drug to the upper nasal cavity, which is highly vascularised and absorptive, unlike existing nasal sprays, which only target the lower nasal cavity. In clinical trials, this technology improved the drug’s efficacy and the onset of action compared to oral and injectable alternatives.

There is a growing awareness that nasal drug delivery can provide better efficacy and faster relief compared to traditional oral therapies in the acute treatment of patients with migraine, particularly those who suffer from gastrointestinal comorbidities such as nausea, vomiting and gastroparesis. Nasal delivery is not a new approach to managing acute migraine attacks, however. The migraine market is crowded with various brands such as Bausch’s Migranal (DHE), GlaxoSmithKline’s Imitrex (sumatriptan) and AstraZeneca ’s Zomig (zolmitriptan). And in the last decade, the acute migraine market has become saturated with generics, as most branded drugs are off-patent.

Despite this, physicians have suggested that nasal products see low utilisation because patients complain about their taste and require some coaching on how to use the device for the first time, as opposed to traditional oral forms. This could be a missed opportunity for better acute control of migraine aspects in some patients. As such, INP104’s unique POD system is likely its most anticipated feature, and is expected to somewhat drive its initial uptake by capturing some new patients as well as those switching from old nasal products.