OPEN-LABEL DOSE-ESCALATION DATA FROM THE RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY TO ASSESS THE SAFETY AND EFFICACY OF PULSED, INHALED NITRIC OXIDE (INO) IN SUBJECTS AT RISK OF PULMONARY HYPERTENSION ASSOCIATED WITH PULMONARY FIBROSIS (PH-PF) ON LONG TERM OXYGEN THERAPY

Abstract

SESSION TITLE: Late Breaking Abstracts SESSION TYPE: Original Investigations PRESENTED ON: 10/23/2019 10:45 AM ‐ 11:45 AM PURPOSE: Pulmonary fibrosis (PF) is made up of a variety of fibrotic lung diseases, the largest of which is IPF (Idiopathic Pulmonary Fibrosis). Pulmonary hypertension (PH) frequently complicates PF and is associated with impaired functional capability, lower physical activity, poor quality of life and significantly reduced life expectancy. Inhaled Nitric Oxide (iNO) at a dose of 30 mcg/kg IBW/hr (Cohort 1) has been demonstrated to improve moderate to vigorous physical activity (MVPA) by 34% (placebo‐corrected) in an 8‐week controlled trial. After completion of the 8‐week placebo‐controlled trial, subjects were transitioned from blinded treatment to open label treatment at 45 mcg/kg IBW/hr (iNO45) and 75 mcg/Kg IBW/hr (iNO75) in a stepwise manner. METHODS: Subjects in Cohort 1 were randomized to receive iNO 30 (n=23) or placebo (n=18) for 8 weeks of blinded treatment, after which subjects transitioned to iNO45 for at least 8‐weeks and then to iNO75. A wrist‐worn medical grade activity monitor was used to assess changes in daily activity during the open label period. Safety and efficacy parameters were also evaluated. RESULTS: During blinded treatment subjects on iNO30 remained stable while subjects on placebo experienced on average a 4% drop in MVPA (walking, stairs, yardwork, etc.) per week. During open label treatment with iNO45, subjects saw an average increase in MVPA of 1% per week (n=17), including subjects on placebo who transitioned from a decline in the placebo‐controlled part of the study to an increase in MVPA in the open label extension period. Subjects who continued into iNO75 (n=10) maintained an average increase of 1% per week in MVPA. The iNO45 and iNO75 doses were both safe and well tolerated. CONCLUSIONS: iNO 30 demonstrated clinically and statistically meaningful improvements in moderate and overall activity compared to placebo over an 8 week period. In the open label extension, higher doses of iNO were also safe and well tolerated while continuing to show continued improvement in activity parameters. CLINICAL IMPLICATIONS: There are currently no approved therapies to treat PH‐PF as systemic vasodilators used in Pulmonary Arterial Hypertension (PAH) have proven to be ineffective in PH‐PF. Although a relatively small sample size, the placebo‐controlled data with iNO30 has demonstrated the ability to improve activity capacity in patients with PH‐PF who are known to be limited in their ability to conduct activities of daily living. The placebo‐controlled data with iNO30 also demonstrated an improvement in oxygen saturations during the 6MWT. Now these data are supported by the findings from higher doses in the open label extension study. A large, pivotal (registrational) phase 3 study of iNO in patients with PF on long term oxygen therapy and at risk of PH will commence in 2020, using the change in MVPA as the primary endpoint. DISCLOSURES: no disclosure on file for Roger Alvarez; no disclosure on file for Neil Ettinger; no disclosure on file for Peter Fernandes; Consultant relationship with Veracyte Please note: $1001 ‐ $5000 Added 03/18/2019 by Kevin Flaherty, source=Web Response, value=Consulting fee Consultant relationship with Boehringer Ingelheim Please note: $20001 ‐ $100000 Added 03/18/2019 by Kevin Flaherty, source=Web Response, value=Consulting fee Consultant relationship with Roche/Genentech Please note: $5001 ‐ $20000 Added 03/18/2019 by Kevin Flaherty, source=Web Response, value=Consulting fee Consultant relationship with Bellapheron Please note: $1001 ‐ $5000 Added 03/18/2019 by Kevin Flaherty, source=Web Response, value=Consulting fee Consultant relationship with Bellerophon Please note: $20001 ‐ $100000 Added 06/20/2019 by Hunter Gillies, source=Web Response, value=Consulting fee Advisory Committee Member relationship with Genentech Please note: $1001 ‐ $5000 Added 06/10/2019 by Marilyn Glassberg, source=Web Response, value=Honoraria Advisory Committee Member relationship with Boehringer Ingelheim Please note: $1001 ‐ $5000 Added 06/10/2019 by Marilyn Glassberg, source=Web Response, value=Honoraria Consultant relationship with Genentech Please note: $1001 ‐ $5000 Added 06/10/2019 by Marilyn Glassberg, source=Web Response, value=Consulting fee Advisory Committee Member relationship with Bellerophon Please note: $1001 ‐ $5000 Added 06/10/2019 by Marilyn Glassberg, source=Web Response, value=Honoraria Research Award relationship with Genentech/Roche Please note: >$100000 Added 06/10/2019 by Marilyn Glassberg, source=Web Response, value=Grant/Research Consultant relationship with Bristol Myers Squibb Please note: $1‐$1000 Added 06/10/2019 by Marilyn Glassberg, source=Web Response, value=Consulting fee Advisory Committee Member relationship with RedX Pharma Please note: $1001 ‐ $5000 Added 06/10/2019 by Marilyn Glassberg, source=Web Response, value=Consulting fee Scientific Medical Advisor relationship with Boehringer Ingelheim Please note: $5001 ‐ $20000 Added 06/10/2019 by Marilyn Glassberg, source=Web Response, value=Consulting fee Speaker/Speaker's Bureau relationship with Genentech Please note: $20001 ‐ $100000 Added 07/03/2019 by Lisa Lancaster, source=Web Response, value=Honoraria Consultant relationship with Galapagos Please note: $1001 ‐ $5000 Added 07/03/2019 by Lisa Lancaster, source=Web Response, value=Consulting fee Speaker/Speaker's Bureau relationship with Boehringer ingelheim Please note: $1001 ‐ $5000 Added 07/03/2019 by Lisa Lancaster, source=Web Response, value=Honoraria Consultant relationship with Bellerophon Please note: $1001 ‐ $5000 Added 07/03/2019 by Lisa Lancaster, source=Web Response, value=Honoraria PI relationship with celgene Please note: $20001 ‐ $100000 Added 07/03/2019 by Lisa Lancaster, source=Web Response, value=Grant/Research PI relationship with Novartis Please note: $20001 ‐ $100000 Added 07/03/2019 by Lisa Lancaster, source=Web Response, value=Grant/Research Support PI relationship with Biogen Please note: $20001 ‐ $100000 Added 07/03/2019 by Lisa Lancaster, source=Web Response, value=Grant/Research Support PI relationship with Biogen Please note: $20001 ‐ $100000 Added 07/03/2019 by Lisa Lancaster, source=Web Response, value=Grant/Research Support Removed 07/03/2019 by Lisa Lancaster, source=Web Response PI relationship with Biogen Please note: $20001 ‐ $100000 Added 07/03/2019 by Lisa Lancaster, source=Web Response, value=Grant/Research Support Removed 07/03/2019 by Lisa Lancaster, source=Web Response PI relationship with Galapagos Please note: $1001 ‐ $5000 Added 07/03/2019 by Lisa Lancaster, source=Web Response, value=Grant/Research Support PI relationship with Bellerophon Please note: $20001 ‐ $100000 Added 07/03/2019 by Lisa Lancaster, source=Web Response, value=Grant/Research Support My spouse/partner as a Employee relationship with Medtronic Please note: >$100000 Added 07/03/2019 by Lisa Lancaster, source=Web Response, value=Salary No relevant relationships by James Loyd, source=Admin input Consultant relationship with Roche‐Genentech Please note: $20001 ‐ $100000 Added 03/15/2019 by Steven Nathan, source=Web Response, value=Consulting fee Speaker/Speaker's Bureau relationship with Boerhinger‐Ingelheim Please note: $20001 ‐ $100000 Added 03/15/2019 by Steven Nathan, source=Web Response, value=Honoraria Consultant relationship with Promedior Please note: $5001 ‐ $20000 Added 03/15/2019 by Steven Nathan, source=Web Response, value=Consulting fee Consultant relationship with Bellerophon Please note: $5001 ‐ $20000 Added 03/15/2019 by Steven Nathan, source=Web Response, value=Consulting fee Advisory Committee Member relationship with United Therapeutics Please note: $1001 ‐ $5000 Added 03/15/2019 by Steven Nathan, source=Web Response, value=Consulting fee no disclosure on file for Ganesh Raghu; Employee relationship with Bellerophon Therapeutics Please note: >$100000 Added 06/26/2019 by Parag Shah, source=Web Response, value=Salary Board Member relationship with Live Fully, Inc. Please note: $1‐$1000 Added 06/22/2019 by Jeffrey Swigris, source=Web Response, value=Intellectual property rights Scientific Medical Advisor relationship with Genentech Please note: $1001 ‐ $5000 Added 06/22/2019 by Jeffrey Swigris, source=Web Response, value=Honoraria Speaker/Speaker's Bureau relationship with Genentech Please note: $1001 ‐ $5000 Added 06/22/2019 by Jeffrey Swigris, source=Web Response, value=Honoraria Speaker/Speaker's Bureau relationship with Boehringer Ingelheim Please note: $1001 ‐ $5000 Added 06/22/2019 by Jeffrey Swigris, source=Web Response, value=Honoraria