nerandomilast (BI 1015550) / Boehringer Ingelheim - LARVOL DELTA

A Study to Test Whether Nerandomilast Helps People With Lungfibrosis Related to Rheumatic Diseases (clinicaltrials.gov) - P3 | N=400 | Not yet recruiting | Sponsor: Boehringer Ingelheim

New P3 trial • Immunology • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases • Rheumatology

Boehringer Ingelheim’s first-in-class pulmonary fibrosis therapy granted priority review [Google translation] (Sohu.com) - "On January 24, the Center for Drug Evaluation (CDE) of the National Medical Products Administration officially granted priority review and approval to Boehringer Ingelheim's nerandomilast tablets, whose proposed indication is for the treatment of idiopathic pulmonary fibrosis (IPF) in adults....The pivotal Phase III clinical study FIBRONEER-IPF is the largest Phase III clinical study in the field of IPF treatment to date."

China approval • Priority review • Idiopathic Pulmonary Fibrosis

FIBRONEER-IPF: A Study to Find Out Whether BI 1015550 Improves Lung Function in People With Idiopathic Pulmonary Fibrosis (IPF) (clinicaltrials.gov) - P3 | N=1177 | Completed | Sponsor: Boehringer Ingelheim | Active, not recruiting ➔ Completed

Trial completion • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

Rationale for phosphodiesterase-4 inhibition as a treatment strategy for interstitial lung diseases associated with rheumatic diseases. (PubMed, RMD Open) - "The potential clinical benefit of PDE4B inhibition is now being investigated in the phase III setting, with two trials evaluating nerandomilast in patients with IPF (FIBRONEER-IPF) or with progressive pulmonary fibrosis other than IPF (FIBRONEER-ILD). Here, we review the preclinical and clinical data that provide rationale for PDE4B inhibition as a treatment strategy in patients with SARD-ILD."

Journal • Review • Fibrosis • Gastrointestinal Disorder • Idiopathic Pulmonary Fibrosis • Immunology • Inflammation • Inflammatory Arthritis • Interstitial Lung Disease • Musculoskeletal Diseases • Pulmonary Disease • Respiratory Diseases • Rheumatoid Arthritis • Rheumatology • Scleroderma • Systemic Sclerosis

A Study in Healthy People to Compare 2 Different Formulations of Nerandomilast Tablets When Taken With or Without Food (clinicaltrials.gov) - P1 | N=15 | Completed | Sponsor: Boehringer Ingelheim | Active, not recruiting ➔ Completed

Trial completion

A Study in Healthy People to Compare 2 Different Formulations of Nerandomilast Tablets When Taken With or Without Food (clinicaltrials.gov) - P1 | N=15 | Active, not recruiting | Sponsor: Boehringer Ingelheim | Recruiting ➔ Active, not recruiting

Enrollment closed

Design of CONQUEST, a novel, randomized, placebo-controlled, Phase 2b platform clinical trial to investigate new treatments for patients with early active systemic sclerosis with interstitial lung disease. (PubMed, J Scleroderma Relat Disord) - P2 | "The first molecules to be studied, amlitelimab and nerandomilast, both have a strong scientific rationale to modify underlying disease processes in systemic sclerosis. Platform Clinical Study for Conquering Scleroderma (CONQUEST); NCT06195072; https://www.clinicaltrials.gov/study/NCT06195072."

Journal • P2b data • Immunology • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases • Rheumatology • Scleroderma • Systemic Sclerosis

Nerandomilast Improves Bleomycin-Induced Systemic Sclerosis-Associated Interstitial Lung Disease in Mice by Regulating the TGF-β1 Pathway. (PubMed, Inflammation) - "Besides nintedanib and tocilizumab, there are currently no clinically approved drugs for SSc-ILD, highlighting the urgent need for new treatment strategies. Our research demonstrates that nerandomilast effectively inhibits skin and lung fibrosis in a bleomycin-induced mouse model of SSc-ILD. For lung fibrosis, we found that nerandomilast could improve bleomycin-induced SSc-ILD through inhibiting PDE4B and the TGF-β1-Smads/non-Smads signaling pathways, which provides a theoretical basis for potential therapeutic drug development for SSc-ILD."

Journal • Preclinical • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases • Rheumatology • Scleroderma • Systemic Sclerosis • TGFB1

BAYESIAN APPROACH FOR ELEVATE IPF: RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL TO EVALUATE EFFICACY, SAFETY, AND DOSE RESPONSE OF DEUPIRFENIDONE (LYT-100) IN IPF (CHEST 2024) - "There is precedent for leveraging Bayesian methodology in IPF studies (i.e., phase 2 programs for BI 1015550 and BMS-986278) to minimize the number of patients exposed to placebo while still generating data sufficient for decision making in drug development...The study will evaluate approximately 240 treatment-naïve adult participants, or those with less than 6 months exposure to nintedanib, at least 40 years of age at approximately 120 study centers globally... The Bayesian dynamic borrowing approach leverages the plethora of placebo data available from prior IPF studies. This approach has the potential to significantly enhance the statistical power of this study while limiting the number of patients required to be treated with placebo. CLINICAL IMPLICATIONS: Bayesian dynamic borrowing allows for historic IPF controls to complement clinical trial data to maximize the number of patients exposed to active treatment arms and minimize the number exposed to placebo."

Clinical • Idiopathic Pulmonary Fibrosis • Immunology • Oncology • Rare Diseases

A Study in Healthy People to Compare 2 Different Formulations of Nerandomilast Tablets When Taken With or Without Food (clinicaltrials.gov) - P1 | N=15 | Recruiting | Sponsor: Boehringer Ingelheim | Not yet recruiting ➔ Recruiting

Enrollment open

A Study in Healthy People to Compare 2 Different Formulations of Nerandomilast Tablets When Taken With or Without Food (clinicaltrials.gov) - P1 | N=15 | Not yet recruiting | Sponsor: Boehringer Ingelheim

New P1 trial

Boehringer’s nerandomilast meets primary endpoint in pivotal phase-III FIBRONEER-IPF study (GlobeNewswire) - P3 | N=1,177 | FIBRONEER-IPF (NCT05321069) | Sponsor: Boehringer Ingelheim | "Full efficacy and safety data from the trial will be presented in the first half of 2025. Boehringer Ingelheim will submit a new drug application for nerandomilast for the treatment of IPF to the US FDA and other Health Authorities worldwide....Boehringer Ingelheim announced today that the FIBRONEER-IPF trial met its primary endpoint, which was the absolute change from baseline in Forced Vital Capacity [mL] (FVC) at week 52 versus placebo. FVC is a measure of lung function."

Filing • P3 data • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease

A Study in Healthy People to Compare How 2 Different Low Dose Formulations of BI 1015550 Are Taken up in the Body (clinicaltrials.gov) - P1 | N=64 | Completed | Sponsor: Boehringer Ingelheim | Active, not recruiting ➔ Completed

Trial completion

A Study in Healthy People to Compare How 2 Different High Dose Formulations of BI 1015550 Are Taken up in the Body (clinicaltrials.gov) - P1 | N=64 | Completed | Sponsor: Boehringer Ingelheim | Recruiting ➔ Completed

Trial completion

Wow! Boehringer-Ingelheim announces that Nerandomilast meets primary endpoint in pivotal phase-III FIBRONEER™-IPF study - a decade after the first positive phase III trials for IPF. Cannot wait to see the full results but this EXCITING !!! #CureIPF https://boehringer-ingelheim.com/us/topline-results-boehringers-phase-iii-ipf-study

P3 data • Idiopathic Pulmonary Fibrosis

Effects of nerandomilast, a preferential PDE4B inhibitor, on metabolism of midazolam, a sensitive CYP3A substrate (ERS 2024) - "Induction of CYP2C enzymes by nerandomilast is also not expected since both CYP3A and CYP2C enzymes are induced via activation of the same pathway, pregnane X receptor. Therefore, nerandomilast is not expected to affect the systemic exposure of drugs that are mainly metabolized by CYP3A and CYP2C enzymes."

Idiopathic Pulmonary Fibrosis • Immunology • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases • CYP2C19 • CYP3A4

Design of the FIBRONEER-ON open-label extension trial of nerandomilast (BI 1015550) (ERS 2024) - P3 | "This trial will also monitor long-term efficacy outcomes, including forced vital capacity change, and time to first exacerbation, disease progression, hospitalisation and death. Conclusions This trial will provide information on the long-term safety, tolerability and efficacy of nerandomilast in patients with IPF and PPF."

Clinical • Idiopathic Pulmonary Fibrosis • Immunology • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases

Baseline characteristics of patients enrolled in the FIBRONEER-ILD trial of nerandomilast (BI 1015550) (ERS 2024) - "Conclusions The trial will provide insights into the efficacy and safety of nerandomilast in patients with PPF. These interim data suggest the population may be similar to that of the INBUILD trial."

Clinical • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Infectious Disease • Interstitial Lung Disease • Pneumonia

Potential of phosphodiesterase 4B inhibitors in the treatment of interstitial lung disease associated with autoimmune diseases. (PubMed, Clin Exp Rheumatol) - "The phase III FIBRONEER-ILD trial is evaluating the efficacy and safety of nerandomilast, given alone or on top of nintedanib, in patients with PPF, including PPF associated with autoimmune diseases. In this article, we review the potential of PDE4B inhibition in the treatment of ILD associated with autoimmune diseases, including the pre-clinical and early clinical data available to date."

Journal • Review • Fibrosis • Gastrointestinal Disorder • Idiopathic Pulmonary Fibrosis • Immunology • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases

PDE4B inhibition by nerandomilast: Effects on lung fibrosis and transcriptome in fibrotic rats and on biomarkers in human lung epithelial cells. (PubMed, Br J Pharmacol) - "This study further supports the available knowledge about the anti-inflammatory/antifibrotic mechanisms of nerandomilast and provides novel insights into the mode of action and signalling pathways influenced by nerandomilast treatment of lung fibrosis."

Journal • Preclinical • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Inflammation • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases

Evidence from recent clinical trials in fibrotic interstitial lung diseases. (PubMed, Curr Opin Pulm Med) - "Despite recent frustrating negative results, there is a growing portfolio of candidate drugs developed in both IPF and PPF."

Journal • Review • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases • CTGF

A Study in Healthy People to Test Whether Different Doses of BI 1015550 Have Potential to Induce Heart Rhythm Abnormalities (clinicaltrials.gov) - P1 | N=46 | Completed | Sponsor: Boehringer Ingelheim | Active, not recruiting ➔ Completed

Trial completion

A Study in Healthy People to Compare How 2 Different Low Dose Formulations of BI 1015550 Are Taken up in the Body (clinicaltrials.gov) - P1 | N=64 | Active, not recruiting | Sponsor: Boehringer Ingelheim | Recruiting ➔ Active, not recruiting

Enrollment closed

FIBRONEER™-ON: A Follow-up Study to Test Long-term Treatment With BI 1015550 in People With Pulmonary Fibrosis Who Took Part in a Previous Study With BI 1015550 (clinicaltrials.gov) - P3 | N=1700 | Recruiting | Sponsor: Boehringer Ingelheim | Not yet recruiting ➔ Recruiting

Enrollment open • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

A Study in Healthy People to Test How BI 1015550 is Taken up in the Body When Given With or Without Food (clinicaltrials.gov) - P1 | N=18 | Completed | Sponsor: Boehringer Ingelheim | Active, not recruiting ➔ Completed

Trial completion