Impel NeuroPharma has filed to raise $75 million in an IPO to bring a migraine drug to market. The candidate, Trudhesa, is delivered using a metered dose device intended to get the active ingredient into the upper nasal space.
Trudhesa, formerly known as NP104, is a nasal formulation of dihydroergotamine, a decades-old drug originally given intravenously. Multiple companies have tried to reformulate dihydroergotamine, perhaps most notably MAP Pharmaceuticals and Allergan, but have collectively been stymied by problems with efficacy, manufacturing and delivery. Impel is aiming to succeed where others stumbled when the FDA rules on whether to approve Trudhesa later this year.
Ahead of the September PDUFA date, Impel has filed to raise money to support the launch of Trudhesa and the initiation of a clinical proof-of-concept trial of another asset in autism spectrum disorder. The IPO paperwork offers a look at some of the difficulties Impel has faced in the past and could encounter in the future.
Some of the issues relate to the STOP301 trial of Trudhesa. Impel said increased levels of impurities were found in some drug vials of certain drug lots used in the study. The vials were removed from the study, no safety issues were linked to the impurity and an investigation identified long stoppages in the production of two lots as the likely root cause. Impel set out the explanation at a meeting with the FDA.
"At that time, the FDA did not concur that the investigation had adequately identified the root cause of the presence of impurities. While we have conducted additional investigations that have led us to believe we identified the root cause and we have worked with our CMO to avoid those conditions in future production runs, there is no guarantee that the FDA will agree that our subsequent investigations have adequately identified the root cause, or that our corrective and preventive actions have sufficiently remediated the issue," Impel wrote.
Impel said the FDA “may request more detailed safety analyses, additional product stability data and further investigations into the impurity issue.” The situation could result in the FDA issuing a complete response letter.
The design of the clinical trial means there are limitations to how Impel can use the data if it wins approval. As the efficacy endpoints are exploratory, Impel won’t be able to include any of the data from those analyses in its labeling or “make any broad efficacy claims based on the results of this study.” Impel said the FDA may restrict the use of Trudhesa, for example by ruling that upper nasal cavity drug delivery is inappropriate in chronic rhinitis patients.
Impel plans to bring Trudhesa to market via the 505(b)(2) pathway, enabling it to reference prior studies of dihydroergotamine in support of its application. However, the IPO paperwork warns potential investors the FDA may not agree Impel has provided "a scientific bridge" to show reliance on prior safety or efficacy findings is valid.