(PRNewsfoto/Impel NeuroPharma)

The analgesic dihydroergotamine (DHE) has perhaps the longest track record of any effective migraine medicine.

Seattle-based Impel NeuroPharma (NSDQ:IMPL) aims to reestablish DHE as a cornerstone of acute migraine treatment following the FDA approval of Trudhesa, a DHE nasal spray. Trudhesa uses the company’s Precision Olfactory Delivery (POD) that delivers the drug to the vasculature within the upper nasal cavity.

“I’ve been in this field for 30 years. I still have the privilege of seeing patients, and nothing in the realm of new treatments has quite met that need that DHE fulfills,” said Dr. Sheena K. Aurora, vice president of medical affairs, migraine at Impel NeuroPharma. DHE continues to offer compelling efficacy for, say, patients who wake up in the morning with a migraine and patients with menstrually-associated migraine.

Dr. Sheena K. Aurora

While DHE is currently available as a nasal spray, there are problems with the repeatability when delivering the drug to the lower nasal cavity, said Adrian Adams, chairman and CEO of Impel NeuroPharma. Conversely, delivery to the upper nasal cavity avoids the pitfalls of delivering “to the lower nasal space, where you can get dripping down the back of the throat,” Adams explained. “You can, in essence, swallow efficacy.”

Impel NeuroPharma said its proprietary intranasal delivery method of DHE offers pharmacokinetics similar to IV-based delivery. It does so, however, without the nausea and vomiting sometimes associated with that delivery route.

The migraine treatment landscape has matured in recent years, but many patients remain frustrated. “Most migraine patients pass through triptans,” Adams said, referring to the drug class that became a popular migraine treatment beginning in the 1990s. “But a very significant proportion of patients either do not tolerate it or just don’t get the efficacy. So, we refer to them as triptan failures.”

Adrian Adams

Similarly, gepants, small molecule calcitonin gene-related peptide (CGRP) receptor antagonists, have also grown in popularity. Notable treatments include Nurtec ODT (rimegepant) and Ubrelvy (ubrogepant). “Gepants represent most of the growth within the market at this particular point in time,” Adams said. “But despite this, almost half of the patients who are put on those treatments either switch away or drop off therapy. And the reason for that predominantly is related to disappointments in efficacy or issues related to the broader aspects of tolerance, particularly GI issues, etc.”

While it is challenging to compare the performance of migraine treatments, gepants don’t seem to match the efficacy of triptans, Aurora said. “Patients never know if they’re going to respond to [gepants], and they’re really haven’t been a lot of consistency studies.”

“So, even though there’s been a lot of development in the acute treatment of migraine, nothing really has filled the shoes of the efficacy of DHE,” Aurora said.

“While DHE has been around for many, many years, and is recognized as being a gold standard efficacy product, the challenge has been that it was tough to deliver that gold standard efficacy in a predictable, consistent way,” Adams said. “So by combining DHE with our [POD drug delivery] technology gave that precise delivery.”

In addition to Trudhesa nasal spray, 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.