FAQs on IPF Therapies: Current, Emerging, and Combination Strategies

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with limited treatment options, but several therapies—both approved and emerging—are helping slow disease progression and improve patient outcomes. Understanding their mechanisms, effectiveness, and potential role in combination therapy is critical for clinicians, patients, and payers.

Here are common FAQs about IPF therapies.

What therapies are currently available to treat IPF, and how do they impact disease progression?

There are currently 3 FDA-approved therapies to treat IPF: nerandomalist (JASCAYD; Boehringer Ingelheim), nintedanib (OFEV; Boehringer Ingelheim), and pirfenidone (Esbriet; Genentech).¹ Nerandomilast, an oral phosphodiesterase-4B inhibitor, was approved in 2025 and is the first new IPF therapy approved in more than 10 years. Nintedanib, approved in 2014 along with pirfenidone, is a tyrosine kinase inhibitor that targets multiple growth factor receptors. Pirfenidone is an oral antifibrotic and anti-inflammatory therapy. All 3 drugs have been shown to slow the rate of forced vital capacity decline in patients with IPF.

More recently, the FDA and the European Commission granted orphan drug designation to support the late-stage development of the drug deupirfenidone, an antifibrotic and deuterated form of pirfenidone.²

How effective are antifibrotic therapies in slowing disease progression?

Although there is no absolute cure for IPF, many of the approved therapies, alone and in combination, have been shown to slow the rate of disease progression. Antifibrotics, like nintedanib and pirfenidone specifically, have proven the ability to extend survival in patients with progressive fibrosing interstitial lung disease (PF-ILD); the same benefits are not generalizable to all patients with progressive PF (PPF).³

Moreover, an overwhelming number of patients with IPF experience adverse events that frequently impact their quality of life, despite treatment with antifibrotics. Although the majority of 106 patients surveyed said that the treatment “gave them hope” and helped slow the progression of their disease, approximately 90% said they experienced at least 1 adverse event as a result of treatment. ⁴

What evidence supports the cost-effectiveness of antifibrotic treatments for IPF?

A systematic review, including 9 studies that evaluated and compared the cost-effectiveness of pirfenidone with nintedanib, found that nintedanib was more cost-effective. The incremental cost-effectiveness ratios ranged from $66,434 to $1,668,320 per quality-adjusted life year in the US.⁵

What emerging therapies or mechanisms are in the pipeline for pulmonary fibrosis?

Several therapies targeting idiopathic pulmonary fibrosis (IPF) are in late-stage clinical development, with a focus on antifibrotic and anti-inflammatory pathways. Among the most advanced is inhaled treprostinil, which has shown positive results in phase 3 trials, including the TETON2 clinical trial (NCT05255991). Although already FDA-approved for pulmonary hypertension associated with interstitial lung disease, its potential role in IPF may bring it closer to clinical use in this population.⁶

Other investigational therapies in phase 3 trials are exploring novel mechanisms, including modulation of fibrotic signaling pathways and inflammation. As the pipeline evolves, these late-stage studies will be critical in determining which therapies may expand treatment options beyond currently approved antifibrotic agents.

What role does combination therapy play in IPF management?

Combination therapy in IPF is an area of ongoing investigation, particularly for patients who continue to progress despite treatment with approved antifibrotic agents such as nintedanib or pirfenidone. Emerging therapies, including agents like nerandomilast, have shown efficacy when added to background antifibrotic therapy, suggesting a potential role for combination approaches in slowing disease progression.

However, the role of immunomodulation in IPF remains unclear. Prior studies, including the PANTHER-IPF trial, demonstrated harm with certain immunosuppressive therapies, highlighting the need for caution. While immunomodulatory strategies may have relevance in other progressive fibrosing interstitial lung diseases, their benefit in IPF has not been established. Ongoing studies are evaluating whether combination approaches targeting complementary pathways can improve outcomes without increasing risk.⁷

References

1. Hannemann K. What are the latest treatments for IPF? Drugs.com. December 29, 2025. Accessed March 13, 2026. https://www.drugs.com/medical-answers/what-latest-treatments-idiopathic-pulmonary-fibros-3581204/

2. McCrear S. FDA and European Commission grant orphan drug status to deupirfenidone for IPF. AJMC^®. March 13, 2026. Accessed March 13, 2026. https://www.ajmc.com/view/fda-and-european-commission-grant-orphan-drug-status-to-deupirfenidone-for-ipf

3. Kaltwasser J. Antifibrotic therapy effective for certain patients with PPF. AJMC. September 22, 2025. Accessed March 13, 2026. https://www.ajmc.com/view/antifibrotic-therapy-effective-for-certain-patients-with-ppf

4. AJMC Contributor. Patients with IPF face QOL challenges with antifibrotic treatment. AJMC. May 27, 2025. Accessed March 13, 2026. https://www.ajmc.com/view/patients-with-ipf-face-qol-challenges-with-antifibrotic-treatment

5. Rezapour Z, Veysi-Sheikhrobat M, Souresrafil A, et al. Cost-effectiveness of nintedanib versus pirfenidone in the treatment of idiopathic pulmonary fibrosis: a systematic review. Expert Rev pharmacoecon Outcomes Res. 2024;25(5):661-669. doi: 10.1080/14737167.2025.2480718

6. Nathan SD, Smith P, Deng C, et al. Inhaled treprostinil for idiopathic pulmonary fibrosis. N Engl J Med. Published online March 11, 2026. Accessed March 17, 2026. doi:10.1056/NEJMoa2512911

7. Haumschild R, Glassberg MK, Adegunsoye A, Pope J. The synergistic approach: exploring potential for combination therapies in fibrosis control. AJMC. July 2, 2025. Accessed March 13, 2026. https://www.ajmc.com/view/the-synergistic-approach-exploring-potential-for-combination-therapies-in-fibrosis-control