IPF Pipeline 2025-2026: Approvals, Failures & Outlook
IPF pipeline 2025-2026: nerandomilast approval, United Therapeutics Phase 3, Pliant discontinuation, BMS-986278 ALOFT progress in pulmonary fibrosis.
Introduction
IPF (Idiopathic Pulmonary Fibrosis) is a rare disease with a poor prognosis, with a median survival of 3-5 years from diagnosis1. Following the 2014 NEJM publications of pirfenidone (ASCEND)2 and nintedanib (INPULSIS-1/-2)3, no new drug class reached the market for over a decade. The year 2025 was one of contrasts: the long silence was broken by a new approval, while a leading candidate was discontinued for safety reasons.
This article analyzes the 2025 IPF development race from the perspectives of approvals and discontinuations, grounded in primary peer-reviewed literature, FDA actions, and corporate IR releases.
[!TIP] Cross-disease market view To place IPF developments such as the first new approval in a decade (Nerandomilast) and the TETON-2 success within the broader fibrosis drug market — including MASH and CKD market sizes, deals, and pipeline opportunities — see Fibrosis Drug Market 2026: IPF, MASH, CKD Forecasts.
Historical Context: A Decade of Stagnation (2014-2024)
The era of antifibrotic therapy in IPF began in 2014 with two pivotal Phase 3 trials published in the same NEJM issue:
- Pirfenidone (ASCEND): 555 patients; 52-week FVC decline significantly reduced versus placebo2
- Nintedanib (INPULSIS-1/-2): 1,066 patients across twin trials; annual FVC decline reduced by ~50%3
However, both antifibrotic agents only slow disease progression — they do not restore lung function or dramatically extend survival. The 2022 ATS/ERS/JRS/ALAT joint clinical practice guideline formally introduced the concept of "Progressive Pulmonary Fibrosis (PPF)"14, broadening the antifibrotic target population beyond IPF to include other progressive fibrotic ILDs.
Throughout this decade, multiple novel mechanisms (αvβ6 integrin, LPA1, PDE4B, autotaxin) advanced into clinical trials, but none reached Phase 3 approval — until 2025.
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IPF in 2025: Approvals and Discontinuations
Approvals
Boehringer Ingelheim - Nerandomilast (JASCAYD®)
- → Deep dive: Nerandomilast (PDE4B Inhibitor): Mechanism, Clinical Data & Preclinical Evidence
- Oral preferential PDE4B inhibitor with combined antifibrotic and immunomodulatory activity5
- FIBRONEER-IPF (NCT05321069): 1,177 patients randomized 1:1:1 to nerandomilast 9 mg BID, 18 mg BID, or placebo. Adjusted mean change in FVC at week 52 was −183.5 mL (placebo) vs −114.7 mL (18 mg group), an adjusted difference of 68.8 mL (p<0.001)5
- FDA approval (October 7, 2025) for IPF — the first new IPF treatment in over a decade6
- FIBRONEER-ILD (NCT05321082): PPF cohort showed similarly significant FVC preservation7; PPF indication added on December 22, 20258
- Most common adverse event: diarrhea (41.3% in 18 mg group vs 16.0% in placebo)5
- Boehringer Ingelheim also markets nintedanib (Ofev), strengthening IPF/PPF franchise leadership
Phase 3 Ongoing
United Therapeutics - Tyvaso (inhaled treprostinil)
- TETON-2 trial: 597 patients; primary endpoint met (announced September 2025)9
- Tyvaso showed a 95.6 mL improvement in absolute FVC versus placebo at week 52, consistent across background therapy subgroups (nintedanib / pirfenidone / no background)9
- Already approved in 2021 for PH-ILD via the INCREASE trial (NEJM)10; IPF expansion will be supported by combined TETON-2 and TETON-1 (H1 2026 readout) sNDA9
Bristol Myers Squibb - BMS-986278 (Admilparant)
- Oral small-molecule LPA1 (lysophosphatidic acid receptor 1) antagonist. The LPA1 pathway was implicated in pulmonary fibrosis by Tager et al.'s seminal 2008 Nature Medicine preclinical study11
- Phase 2 trial (IPF and PPF cohorts): 60 mg BID significantly slowed FVC decline (IPF 26 weeks; also positive in PPF cohort)12. Asymptomatic hypotension observed in 31.0% (13/42) of patients12
- ALOFT-IPF (NCT06003426): enrolling across 400+ sites in 30+ countries; estimated completion October 202613
- ALOFT-PPF (NCT06025578): parallel trial in PPF14
- Holds FDA Breakthrough Therapy, Fast-Track, and Orphan Drug Designations15
Discontinuations
Pliant Therapeutics - Bexotegrast (PLN-74809)
- Oral αvβ6/αvβ1 integrin antagonist that blocks TGF-β activation16
- INTEGRIS-IPF Phase 2a previously demonstrated favorable tolerability and an exploratory antifibrotic signal at the 320 mg dose16
- March 3, 2025: BEACON-IPF Phase 2b/3 trial halted following Independent Data Safety Monitoring Board (DSMB) review citing imbalance in IPF-related adverse events17
- June 27, 2025: full IPF program discontinued after analysis of complete data confirmed increased disease progression, respiratory hospitalization, and mortality risk in the treatment arm18
- CEO Bernard Coulie, M.D., Ph.D., described the decision as "the right decision to protect patient safety"18
Industry Map: Visualizing IPF Development
The following Mermaid diagram visualizes the major approvals and development status in the IPF space in 2025.
Legend:
- 🟢 Green: Approved/Successful companies
- 🔴 Red: Discontinued companies
Analysis: Contrasts in IPF and Future Outlook
In the IPF space, while Boehringer Ingelheim's Nerandomilast achieved the first new approval in over a decade, Pliant's Bexotegrast was discontinued due to safety issues — underscoring the high safety risks inherent in fibrotic disease drug development. The Bexotegrast failure has been attributed in part to αvβ6 integrin inhibition broadly suppressing TGF-β activation, potentially impacting alveolar epithelial repair mechanisms18.
The successful Nerandomilast (oral PDE4B inhibitor) and Tyvaso (inhaled prostacyclin analog) offer mechanistically distinct options. Three storylines now define the field: (1) Nerandomilast market uptake versus existing antifibrotics, (2) BMS-986278 (Admilparant) ALOFT readouts from 2026, and (3) Tyvaso IPF label expansion via the TETON-1 H1 2026 readout.
Conclusion
The year 2025 was a monumental one for the IPF field, breaking a long silence with the arrival of Nerandomilast (JASCAYD). On the other hand, the discontinuation of Bexotegrast illustrates the difficulties of drug discovery. Moving forward, the market penetration of Nerandomilast, the progress of follow-on drugs like Tyvaso and Admilparant (BMS-986278), and the expansion of treatment options into the newly defined PPF population will be closely watched.
Looking Ahead to 2026
Key storylines to watch as the IPF landscape evolves:
- Nerandomilast (Jascayd) market uptake — Following its October 2025 approval and December 2025 PPF expansion, real-world adoption rates and payer coverage will define whether it can coexist with Ofev rather than cannibalize it within the Boehringer portfolio.
- Tyvaso IPF label expansion — After the TETON-2 pivotal readout in 2025, United Therapeutics' formal FDA interaction and potential IPF-indication filing will be a central 2026 milestone.
- BMS-986278 (Admilparant) Phase 3 ALOFT progress — As the most advanced LPA1-receptor antagonist in development, interim readouts from the ALOFT-IPF and ALOFT-PPF programs will signal whether a third mechanism class can enter the IPF standard of care. See our dedicated BMS-986278 deep dive for the underlying biology and trial design.
- Post-Bexotegrast αvβ6 / integrin strategies — Whether any competitor revives the integrin-targeting approach under revised dosing or patient selection is an open question for the broader anti-fibrotic community.
This section will be updated as new 2026 trial readouts, regulatory actions, and business events occur.
References
1. Raghu G, Remy-Jardin M, Richeldi L, et al. Idiopathic Pulmonary Fibrosis (an Update) and Progressive Pulmonary Fibrosis in Adults: An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline. Am J Respir Crit Care Med. 2022;205(9):e18-e47. PubMed: 35486072
2. King TE Jr, Bradford WZ, Castro-Bernardini S, et al. A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis (ASCEND). N Engl J Med. 2014;370(22):2083-2092. PubMed: 24836312
3. Richeldi L, du Bois RM, Raghu G, et al. Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis (INPULSIS-1 and INPULSIS-2). N Engl J Med. 2014;370(22):2071-2082. PubMed: 24836310
4. Rajan SK, Cottin V, Dhar R, et al. Progressive pulmonary fibrosis: an expert group consensus statement. Eur Respir J. 2023;61(3):2103187. PubMed: 36517177
5. Richeldi L, Azuma A, Cottin V, et al. Nerandomilast in Patients with Idiopathic Pulmonary Fibrosis (FIBRONEER-IPF). N Engl J Med. 2025. PubMed: 40387033
7. Maher TM, Assassi S, Azuma A, et al. Nerandomilast in Patients with Progressive Pulmonary Fibrosis (FIBRONEER-ILD). N Engl J Med. 2025. PubMed: 40388329
10. Waxman A, Restrepo-Jaramillo R, Thenappan T, et al. Inhaled Treprostinil in Pulmonary Hypertension Due to Interstitial Lung Disease (INCREASE). N Engl J Med. 2021;384(4):325-334. PubMed: 33440084
11. Tager AM, LaCamera P, Shea BS, et al. The lysophosphatidic acid receptor LPA1 links pulmonary fibrosis to lung injury by mediating fibroblast recruitment and vascular leak. Nat Med. 2008;14(1):45-54. PubMed: 18066075
12. Corte TJ, Lancaster L, Swigris JJ, et al. Efficacy and Safety of Admilparant, an LPA1 Antagonist, in Pulmonary Fibrosis: A Phase 2 Randomized Clinical Trial. Am J Respir Crit Care Med. 2025;211:230-238. PubMed: 39393084
13. ALOFT-IPF Trial — ClinicalTrials.gov NCT06003426
14. ALOFT-PPF Trial — ClinicalTrials.gov NCT06025578
15. Pulmonary Fibrosis Research — Bristol Myers Squibb (Company Page)
16. Lancaster L, Cottin V, Ramaswamy M, et al. Bexotegrast in Patients with Idiopathic Pulmonary Fibrosis: The INTEGRIS-IPF Clinical Trial. Am J Respir Crit Care Med. 2024. PubMed: 38843105