Liquidia v. FDA
Plus some position updates
There was quite a bit of Twitter action last week following the FDA’s decision to tentatively approve Yutrepia in both PAH and PH-ILD while simultaneously granting United Therapeutics an out-of-the-blue 3 year exclusivity period in both indications, further preventing Liquidia from selling Yutrepia until May of 2025.
The exclusivity was a surprise to everyone involved—including apparently both Liquidia’s and United Therapeutics’ management teams. United, for example, previously said in its 2021 Annual Report that it expected the Tyvaso exclusivity to terminate in March of 2024:
from United Therapeutics 2021 10-K
The basis for this new exclusivity originates in 21 C.F.R. § 314.108, which allows for additional 3-year exclusivity periods for NDAs containing New Clinical Investigations which are essential to the approval of the NDA.
from § 314.108
from 21 U.S.C. § 355(c)(3)(E)(iii)
These investigations must be new efficacy studies, and cannot be “bioavailability studies” (studies which merely demonstrate how much of the active ingredient is actually being absorbed by the patient). More specifically, under 314.108, “New Clinical Investigations” are defined as follows:
from § 314.108
The FDA, in its tentative approval, ruled that the United Therapeutics BREEZE Study, a relatively small and fast, 3 week, 51 patient 2022 study, whose primary objective “was to evaluate the safety and tolerability of treprostinil inhalation powder (TreT) in patients currently treated with treprostinil inhalation solution,” qualified as a new clinical investigation meriting a 3 year exclusivity ending in May of 2025. Importantly, the patients in the BREEZE study were already on stable doses of Tyvaso Inhaled Solution and switching to a corresponding dose of Tyvaso DPI. These were not treprostinil-naive patients.
On its face, this seems like the wrong decision, and more than a bit strange that the FDA raised this sua sponte years into the Yutrepia approval process.
UTHR filed an NDA for Tyvaso DPI for treatment of PAH and PH-ILD under section 501(b)(1) of the FDCA back in April of 2021. The NDA, which was approved in May of 2022, relied on (1) the UTHR TRIUMPH and INCREASE studies, (2) bioavailability data, and (3) the BREEZE study mentioned above. Notably, the TRIUMPH and INCREASE studies had already been submitted to the FDA in UTHR’s 2008 and 2020 Tyvaso Inhaled Solution and supplemental NDAs, respectively. In other words, the only new data which could be argued to be a new clinical investigation was the BREEZE study. Further still, because these were not treprostinil-naive patients in the BREEZE study, it seems that, if any exclusivity should be granted to UTHR at all, it should exclude any treprostinil-naive patients, thereby allowing Liquidia to immediately commercialize in a “new” PAH and PH-ILD patient population.