IPF Pipeline at Inflection: Nerandomilast and Treprostinil Test Combination-Era Payer Logic Without Survival Data

ERS 2026 Highlights New Pulmonary Fibrosis Research

A recent GlobalData Healthcare podcast discussed insights from the 2026 European Respiratory Society (ERS) Conference, held September 5–9 in Barcelona, Spain. The discussion highlighted emerging research in pulmonary fibrosis, a field gaining significant momentum. Key updates included findings on Boehringer Ingelheim’s Jascayd (nerandomilast), which are expected to influence treatment and payer decisions, and positive data from United Therapeutics for inhaled treprostinil in Idiopathic Pulmonary Fibrosis (IPF). The podcast also touched upon signals from clinical trials in chronic cough, an area that has seen previous challenges.

• The 2026 European Respiratory Society (ERS) Conference, which took place from September 5–9 in Barcelona, Spain, served as a crucial platform for showcasing emerging research in the pulmonary fibrosis space. The conference featured in-depth scientific discussions on treatments for both idiopathic pulmonary fibrosis (IPF) and progressive pulmonary fibrosis (PPF), indicating a renewed focus and increased activity in this therapeutic area.
• Boehringer Ingelheim’s drug Jascayd (nerandomilast) was a significant highlight at ERS 2026, with new research findings presented. These findings are anticipated to have a substantial impact on future treatment paradigms and payer decisions for patients with pulmonary fibrosis, potentially leading to shifts in clinical practice and market access strategies for the drug.
• Beyond Boehringer Ingelheim, United Therapeutics also presented positive clinical data for its inhaled treprostinil in Idiopathic Pulmonary Fibrosis (IPF). This progress in the pulmonary fibrosis field is compared to the significant advancements seen in 2014, when Boehringer Ingelheim’s Ofev (nintedanib) and Roche’s Esbriet (pirfenidone) received approvals, underscoring a period of accelerated development.

Navigating the Challenges in Pulmonary Fibrosis Treatment

Despite meaningful advances in antifibrotic therapy, IPF remains a disease with a poor prognosis and significant unmet need. Approved agents slow progression but do not halt or reverse fibrosis, and a range of clinical, pharmacological, and biological challenges continue to limit their real-world impact.

• Survival benefit remains limited. In a real-world Japanese cohort of 102 IPF patients receiving antifibrotic drugs, the median survival from therapy initiation was 38.0 months (95% CI: 25.9–50.1 months), underscoring that even with treatment, long-term outcomes remain poor.

• Adverse event burden threatens treatment continuity. Nintedanib is associated with a high rate of gastrointestinal adverse events — diarrhea was reported in 72.3% of patients in the INBUILD trial — leading to dose reductions and/or treatment interruptions in 48.2% of nintedanib-treated patients. In elderly IPF patients specifically, the incidence of adverse events such as diarrhea, nausea, and elevation of hepatic enzymes is significantly higher, though discontinuation rates were comparable to non-elderly patients when adverse events were actively managed.

• Dose reduction is common with pirfenidone, though its clinical impact is debated. In a South Korean post-marketing surveillance study of 143 IPF patients, 70.6% experienced at least one dose reduction during 48-week follow-up. While pulmonary function changes and rates of death, hospitalization, and acute exacerbation did not differ significantly across dose groups, the reliance on dose modification reflects the difficulty of maintaining standard therapeutic exposure.

• Heterogeneous treatment response is not yet addressable in clinical practice. Latent class analysis across two multicenter cohorts (discovery n = 875; validation n = 347) identified two distinct molecular endotypes of IPF with divergent outcomes. Significant heterogeneity in antifibrotic treatment effect was observed between endotypes (P = 0.030 for interaction), with a favorable response in class 2 (HR, 0.64; 95% CI, 0.45–0.93; P = 0.018) but not in class 1 (HR, 1.19; 95% CI, 0.77–1.84; P = 0.422). No precision medicine approach currently exists to stratify patients prospectively.

• Acute exacerbation remains a poorly controlled and high-mortality event. Corticosteroids remain the primary treatment for acute exacerbation of IPF (AE-IPF), yet dosing and tapering protocols remain controversial, and corticosteroids combined with intravenous cyclophosphamide have been shown to be detrimental to prognosis. While pirfenidone and nintedanib have been shown to reduce the incidence of AE, no intervention has demonstrated clear effectiveness and safety once an exacerbation occurs.

• The role of GERD management in IPF remains unresolved. GERD prevalence among IPF patients was 65.6% in one ILD clinic study, and GERD-associated microaspiration is hypothesized to accelerate fibrotic progression. Although the international IPF guideline recommends antacid therapy regardless of symptomatic GERD, several national guidelines do not support this recommendation due to conflicting data, leaving clinicians without consensus guidance.

ERS 2026: Jascayd and Inhaled Treprostinil Data

Recent clinical investigation in idiopathic pulmonary fibrosis (IPF) has evaluated a range of interventional strategies, from novel biologics to combination antifibrotic regimens. The studies below highlight key efficacy and safety findings across distinct therapeutic approaches.

• BG00011 (Anti-αvβ6 Monoclonal Antibody) — Phase IIb Randomized Trial (NCT03573505): 106 patients were randomized 1:1 to once-weekly subcutaneous BG00011 56 mg or placebo. The primary endpoint was FVC change from baseline at Week 52; due to early termination, endpoints were evaluated at Week 26 as an exploratory analysis. There was no significant difference in FVC change from baseline between BG00011 and placebo at Week 26 (least squares mean [SE] −0.097 L [0.0600] vs. −0.056 L [0.0593]; P = 0.268). After Week 26, patients in the BG00011 group showed a worsening trend; 8 (44.4%) of 18 BG00011 patients versus 4 (18.2%) of 22 placebo patients showed worsening of fibrosis on high-resolution computed tomography. IPF exacerbation/progression was reported in 13 patients, all in the BG00011 group. Serious adverse events occurred more frequently in BG00011 patients, including four deaths. The results do not support continued clinical development of BG00011.

• Vismodegib plus Pirfenidone — Phase 1b Open-Label Trial (NCT02648048): 21 patients with IPF received vismodegib 150 mg plus pirfenidone 2403 mg/day. All patients reported at least one treatment-emergent adverse event, most frequently muscle spasms (76.2%). Serious adverse events were reported in 14.3% of patients; one event of dehydration was considered related to vismodegib. One patient died due to IPF progression, unrelated to either treatment. More patients discontinued vismodegib than pirfenidone (42.9% vs. 33.3%, respectively). Changes from baseline to Week 24 in % predicted FVC and UCSD-SOBQ scores were within known endpoint variability. Vismodegib had no effect on circulating CXCL14 levels. The safety profile was consistent with the known profiles of both drugs, with no new safety signals observed.

• Nintedanib — Global Pharmacovigilance Analysis (2014–2018): Across an estimated cumulative exposure of 60,107 patient-years, diarrhea was the most frequent adverse event (301.6 events per 1,000 patient-years), with 97.0% of diarrhea events classified as non-serious; median time to first diarrhea event was 60 (25th, 75th percentile: 11, 182) days. Elevated liver enzyme or bilirubin levels were reported at 31.5 events per 1,000 patient-years. Bleeding occurred at 36.8 events per 1,000 patient-years (81.0% non-serious). Major cardiovascular adverse events were reported at 13.4 events per 1,000 patient-years, myocardial infarction at 4.3 events per 1,000 patient-years, and gastrointestinal perforation at 1.0 event per 1,000 patient-years. The safety profile was consistent with clinical trial data and the product label, with no new safety concerns identified.

Assessing Jascayd and Treprostinil in the IPF Landscape

Bexotegrast (PLN-74809), an investigational oral integrin inhibitor, has been evaluated alongside standard-of-care IPF therapies — pirfenidone and nintedanib — in the INTEGRIS-IPF Phase 2a trial, offering a direct comparative context. Both approved agents and the investigational compound have been assessed on FVC decline, tolerability, and survival-relevant endpoints across multiple published studies.

ERS Insights: Reshaping Treatment for Fibrotic Lung Diseases and Chronic Cough

The recent European Respiratory Society (ERS) Conference has illuminated critical advancements and ongoing challenges across the landscape of severe lung diseases, offering a glimpse into future therapeutic strategies. For patients battling progressive pulmonary fibrosis (PPF) and idiopathic pulmonary fibrosis (IPF), the data surrounding Boehringer Ingelheim's nerandomilast (Jascayd) is particularly compelling. Studies indicate that nerandomilast not only reduces the decline in forced vital capacity but also significantly lowers the risk of adverse clinical outcomes, including death, in PPF patients. This is a substantial development, especially for those not currently on existing antifibrotic treatments, suggesting a potential new standard of care. However, the literature also points to a nuanced efficacy profile when nerandomilast is co-administered with nintedanib, implying that its optimal positioning within the treatment algorithm—either as monotherapy or in specific combination regimens—will be crucial for market adoption.

In parallel, United Therapeutics' inhaled treprostinil, particularly its dry powder inhaler (DPI) formulation, is gaining traction. While primarily established for pulmonary arterial hypertension (PAH), its utility in pulmonary hypertension associated with interstitial lung disease (PH-ILD), a common comorbidity in IPF, is increasingly recognized. The convenience and improved patient satisfaction associated with the DPI formulation could significantly enhance adherence and broaden its use, offering a more accessible option for managing this complex condition. This represents a strategic advantage in a market where patient quality of life and ease of administration are paramount.

Finally, the chronic cough space, long plagued by limited effective and tolerable treatments, is seeing renewed interest. While earlier P2X3 receptor antagonists like gefapixant faced hurdles, particularly with taste disturbances and mixed efficacy in specific populations like IPF-related cough, the ongoing development of more selective agents in this class offers hope. The challenge remains to deliver robust antitussive effects without the significant taste-related adverse events that have historically impacted patient adherence. Future success in this area will hinge on balancing efficacy with a superior tolerability profile, potentially unlocking a much-needed therapeutic option for millions.