The IPF Pipeline is Set to Deliver: The 3 Top Contenders

Idiopathic pulmonary fibrosis (IPF) remains a progressive and fatal lung disease with few effective therapies and a poor prognosis. At the time of diagnosis, most individuals have a median survival rate of 3 to 4 years. The 5-year survival rate ranges from 20% to 40%.1

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For the approximately 50,000 new cases diagnosed annually in the US,1 currently approved treatments, nintedanib (Ofev; Boehringer Ingelheim) and pirfenidone (Esbriet; Genentech), only modestly slow disease progression and both pose significant tolerability issues, underscoring the urgent need for new approaches. In 2025, multiple investigational drugs are advancing through late-stage trials, offering potential breakthroughs for patients in the near future.

Nerandomilast: Boehringer Ingelheim

Boehringer Ingelheim’s nerandomilast, an oral phosphodiesterase-4B (PDE4B) inhibitor, has emerged as the leading candidate for IPF management after completing the phase 3 FIBRONEER-ILD trial.2 The drug significantly slowed lung function decline in participants with IPF compared with placebo and showed a favorable safety profile and convenient dosing. The FDA recently granted priority review to the New Drug Application for nerandomilast and currently there is a Prescription Drug User Fee Act (PDUFA) decision expected in Q4 2025.3

If approved, nerandomilast would be the first novel therapy for IPF more than a decade.

Admilparant: Bristol Myers Squibb

Admilparant, a lysophosphatidic acid receptor 1 (LPA1) antagonist, significantly delayed time to disease progression over 26 weeks vs placebo in a phase 2 randomized controlled trial.4 LPA1 activation, a distinct mechanism of action, is associated with fibroblast recruitment, activation/proliferation, and survival, as well as epithelial cell apoptosis, all drivers of progressive lung fibrosis.

Based on the phase 2 trial success, Bristol Myers Squibb is advancing admilparant through phase 3 clinical trials (ALOFT-IPF) set to complete in October 2026.4

Inhaled treprostinil: United Therapeutics

United Therapeutics’ treprostinil (Tyvaso), already approved for pulmonary arterial hypertension (PAH) and pulmonary hypertension associated with interstitial lung disease (PH-ILD), is under review for broader IPF use. Results from the phase 3 TETON-2 trial demonstrated a placebo-adjusted absolute forced vital capacity (FVC) improvement of 95.6 mL at week 52 in IPF patients without pulmonary hypertension.5 Eligible participants who complete TETON-2 can enroll in the TETON-OLE open label extension study evaluating the long-term safety and tolerability of nebulized treprostinil in fibrotic lung disease.5

Additional TETON-2 study results will be presented at the European Respiratory Society Congress in Amsterdam on September 28, 2025. The data, along with results from the ongoing TETON-1 study, will support a supplemental New Drug Application to the FDA.5

Success Among Setbacks

The IPF pipeline has seen challenges, including FibroGen’s pamrevlumab and Pliant Therapeutics’ bexotegrast, which failed to meet primary endpoints in phase 3 and phase 2b/3 trials, respectively.

With near-term regulatory decisions on deck for nerandomilast and inhaled treprostinil and admilparant progressing to phase 3 investigation, 2025 has the potential to shift the tides toward more effective and patient-acceptable care for people with IPF.

References

1. Raghu G, Weycker D, Edelsberg J, Bradford WZ, Oster G. Incidence and prevalence of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2006;174(7):810-816. doi:10.1164/rccm.200602-163OC

2. Halsey G. Nerandomilast meets primary endpoint in phase III FIBRONEER-ILD trial in progressive pulmonary fibrosis. Patient Care. February 11, 2025. https://www.patientcareonline.com/view/nerandomilast-meets-primary-endpoint-in-phase-iii-fibroneer-ild-trial-in-progression-pulmonary-fibrosis

3. Global phase III trials demonstrate that nerandomilast slowed lung function decline in IPF and PPF, with similar discontinuation rates to placebo. News release. Boehringer Ingelheim. May 19, 2025. Accessed September 10, 2025. https://www.boehringer-ingelheim.com/human-health/lung-diseases/pulmonary-fibrosis/phase-3-trials-nerandomilast-slowed-lung-function-decline-ipf-and-ppf

4. Maher TM, Wijsenbeek M, Kreuter M, et al. Design and rationale for a phase 3 trial of admilparant (BMS-986278), an oral lysophosphatidic acid receptor 1 antagonist, in patients with idiopathic pulmonary fibrosis: ALOFT-IPF [abstract]. Am J Respir Crit Care Med. 2025;211:A3538. doi:10.1164/ajrccm.2025.211.Abstracts.A3538

5. United Therapeutics Corporation announces TETON-2 pivotal study of Tyvaso meets primary endpoint for the treatment of idiopathic pulmonary fibrosis. News release. United Therapeutics Corporation. September 2, 2025. Accessed September 9, 2025. https://ir.unither.com/~/media/Files/U/United-Therapeutics-IR/documents/press-releases/2025/teton-2-press-release.pdf