Treprostinil Inhalation Powder (Yutrepia) Receives Tentative Approval for PAH and PH-ILD

Credit: US Food and Drug Administration

The US Food and Drug Administration (FDA) has granted tentative approval to treprostinil inhalation powder for the treatment of pulmonary arterial hypertension (PAH) and pulmonary hypertension associated with interstitial lung disease (PH-ILD).

Announced by Liquidia Corporation on August 19, 2024, the company noted tentative approval indicates treprostinil inhalation powder has met all regulatory standards for quality, safety, and efficacy required for approval but must await the expiration of regulatory exclusivity of a competing product before final approval can be granted.¹

“We are pleased that the FDA agreed that our NDA amendment last July was proper, providing a clear path to full approval of YUTREPIA in both PAH and PH-ILD,” said Roger Jeffs, PhD, chief executive officer of Liquidia Corporation.¹ “However, we are disappointed and disagree with the FDA’s decision to simultaneously grant regulatory exclusivity to United Therapeutics for Tyvaso DPI that encompasses chronic use of essentially any dry-powder formulation of treprostinil in the approved indications for a 3-year period for its new dosage form approved on May 23, 2022.”

The rival product referred to by Liquidia Corporation is treprostinil product trademarked as Tyvaso by United Therapeutics. First developed as an inhalation solution, United Therapeutic’s product first received approval in 2009. The inhalation powder version, trademarked as Tyvaso DPI, received approval for treatment for PAH and PH-ILD to improve exercise ability.²

According to the announcement from Liquidia Corporation, the tentative approval of treprostinil inhalation powder is based on data from the phase INSPIRE trial. INSPIRE was an open‐label, multicenter trial and enrolled patients with PAH aged 18 years of age or older who transitioned to treprostinil inhalation powder from nebulized treprostinil or added treprostinil inhalation powder to prostacyclin naïve patients on ≤2 nonprostacyclin oral therapies. The trial’s primary outcomes of interest were safety measures.^1,3

A total of 121 patients were enrolled within the INSPIRE trial. Of these, 29 patients discontinued from the trial, with the most common reason being adverse events. Investigators pointed out 80% of the transition group and 96% of the prostacyclin naïve group titrated to a dose ≥79.5 mcg 4 times daily at day 360, respectively, with one patient achieving a dose of 212 mcg 4 times daily.³

The tentative approval announcement from Liquidia Corporation comes nearly 9 months after the FDA declined to provide a company with an action letter in time for the January 24, 2024 PDUFA date. Before this, the company had submitted a New Drug Application in January 2020 for treprostinil inhalation powder in the management of PAH. In November 2020, the company would announce the receipt of a Complete Response Letter for this NDA. In 2021, the company announced the resubmission of its NDA for the agent for the treatment of PAH to improve exercise ability in adult patients with New York Heart Association Functional Class II-III symptoms, which received tentative approval from the FDA in November 2021. In September 2023, Liquid Corporation announced the FDA’s acceptance of an amendment to the tentatively approved NDA to include the treatment of pulmonary hypertension associated with interstitial lung disease on the label. In September 2023, Liquidia Corporation announced the FDA’s acceptance of an amendment to the tentatively approved NDA to include the treatment of pulmonary hypertension associated with interstitial lung disease on the label.⁴

The August 2024 approval announcement from Liquidia Corporation also pointed out the company is examining treprostinil inhalation powder in the ASCENT trial, an open-label prospective multicenter study, to inform the agent’s dosing and tolerability profile in patients with PH-ILD. The company highlighted it would be seeking full approval for treprostinil inhalation powder as soon as possible.¹

“We plan to take quick action to challenge the FDA’s broad grant of regulatory exclusivity and defend the ability for patients to have access to YUTREPIA with the least delay possible,” Rogers added.¹

References:

1. Liquidia Corporation. U.S. FDA grants tentative approval of YutrepiaTM (treprostinil) inhalation powder for patients with pulmonary arterial hypertension (PAH) and pulmonary hypertension associated with interstitial lung disease (PH-ILD). Liquidia Press Releases. August 19, 2024. Accessed August 19, 2024. https://investors.liquidia.com/news-releases/news-release-details/us-fda-grants-tentative-approval-yutrepiatm-treprostinil.
2. United Therapeutics. United Therapeutics announces FDA approval of Tyvaso DPITM. United Therapeutics Investor Relations. May 24, 2022. Accessed August 19, 2024. https://ir.unither.com/press-releases/2022/05-24-2022.
3. Hill NS, Feldman JP, Sahay S, et al. INSPIRE: Safety and tolerability of inhaled Yutrepia (treprostinil) in pulmonary arterial hypertension (PAH). Pulm Circ. 2022;12(3):e12119. Published 2022 Jul 1. doi:10.1002/pul2.12119
4. Campbell P. Liquidia Corporation: FDA still reviewing NDA to add ph-ild indication for Treprostinil inhalation powder. HCP Live. January 25, 2024. Accessed August 19, 2024. https://www.hcplive.com/view/liquidia-corporation-fda-still-reviewing-nda-to-add-ph-ild-indication-for-treprostinil-inhalation-powder.