TRANSITIONING FROM TYVASO TO LIQ861 IN PULMONARY ARTERIAL HYPERTENSION: A CASE STUDY

Abstract

SESSION TITLE: Pulmonary Vascular Disease Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: October 18-21, 2020 PURPOSE: LIQ861 (Liquidia Technologies) is an investigational, dry-powder formulation of treprostinil designed using PRINT® technology to enhance deep-lung drug deposition and achieve higher dose levels over current nebulized prostacyclin therapies for pulmonary arterial hypertension (PAH) in 1-2 breaths per capsule. INSPIRE (Investigation of the Safety and Pharmacology of Dry Powder Inhalation of Treprostinil) is a Phase 3, open-label, multicenter study of the long-term safety and tolerability of LIQ861. This case evaluates the clinical impact of transitioning treprostinil administration from a Tyvaso® nebulized device to LIQ861 with a dry-powder inhaler. METHODS: A 42-year-old male with ALK1 mutation PAH (functional class [FC] II) and hereditary hemorrhagic telangiectasia was referred to a PAH comprehensive care center for evaluation. Diagnostic hemodynamics were consistent with precapillary PAH. The patient did not tolerate sildenafil or tadalafil due to worsening nosebleeds or macitentan due to fluid retention, and could only tolerate inhaled treprostinil using a Tyvaso® device. He initially titrated to 6 breaths QID but then decreased to 3 breaths QID due to worsening cough. He remained stable in FC II, with an N-terminal pro-brain natriuretic peptide (NT-proBNP) of 30 pg/ml and a 6-minute walk distance (6MWD) of 542 m with no desaturation. He was considered stable to enroll in the INSPIRE study. Assessments at baseline included pulmonary artery pressure of 71/34 mm Hg, mean pulmonary artery pressure of 46 mm Hg, wedge pressure of 13 mm Hg, and pulmonary vascular resistance of 4.6 Wood units. The ESC/ERS risk score was assessed as low with a 6MWD of 558 m, FC II, and NT-proBNP of 62 pg/ml. The total score of the Minnesota Living with Heart Failure Quality of Life (MLWHF) questionnaire was 70. RESULTS: The patient initiated LIQ861 at 26.5 mcg QID. The dose was increased to 53 mcg QID after 4 weeks but reduced to 26.5 mcg QID after 1 week due to worsening cough. An increase to 53 mcg QID was attempted again at Week 8 but immediately decreased to 26.5 mcg QID due to severe cough and desaturation while on oxygen. The dose remained stable at 26.5 mcg QID through Month 12 with no notable adverse events. Assessments at Month 12 showed a risk score maintained as low, including FC II, a 6MWD of 569 m, and NT-proBNP of 124 pg/ml. The MLWHF total score was stable at 69. The patient remained stable on the same dose throughout the duration of the study (2 months), continued to tolerate the same dose a year later, and maintained his low ESC/ERS risk status. CONCLUSIONS: Transition from monotherapy with Tyvaso® to LIQ861 in this patient was well-tolerated and the patient remained stable during the study. CLINICAL IMPLICATIONS: In low-risk PAH patients monotherapy with inhaled prostacyclin LIQ861 is well-tolerated and maintains clinical status. DISCLOSURES: Speaker relationship with Actelion Please note: $5001 - $20000 by Sandeep Sahay, source=Web Response, value=honoraria Speaker relationship with United Therapeutics Please note: $5001 - $20000 by Sandeep Sahay, source=Web Response, value=honoraria speaker relationship with Bayer Please note: $5001 - $20000 by Sandeep Sahay, source=Web Response, value=honoraria My spouse/partner as a Speaker relationship with BTG Please note: $5001 - $20000 by Sandeep Sahay, source=Web Response, value=honoraria brief interview relationship with Liquidia Technologies Please note: $1-$1000 Added 05/26/2020 by Sandeep Sahay, source=Web Response, value=Honoraria