Anti-Fibrotic DMT Pipeline 2026: Pan-Fibrosis Strategy

Introduction: The Paradigm Shift to Disease-Modifying Therapies (DMTs)

For many years, treatments for fibrotic diseases have primarily focused on symptomatic relief. However, with recent advances in therapeutic modalities and a clearer understanding of pathological mechanisms, the development of "anti-fibrotic drugs" as Disease-Modifying Therapies (DMTs)—aimed at delaying progression or even reversing fibrosis—is blossoming.

This article delves into the latest Phase 2 and Phase 3 pipelines, prioritizing the massive markets and high unmet needs of IPF (Idiopathic Pulmonary Fibrosis) and MASH (Metabolic Dysfunction-Associated Steatohepatitis). Additionally, we will explore the potential for expanding these indications to other organs, such as kidneys (CKD) and skin/systemic manifestations (SSc), utilizing a "Pan-fibrosis" approach.

Latest Pipeline: Anti-fibrotic Market Driven by IPF and MASH

The development race for anti-fibrotic drugs is largely driven by two mega-indications: IPF and MASH.

MASH: Dual Approach Targeting Metabolism and Fibrosis

The therapeutic development for MASH predominantly targets normalizing metabolism while actively reversing fibrosis. For more details, refer to our MASH Drug Development Landscape.

• THR-β Agonists (e.g., Resmetirom): Following FDA accelerated approval in March 2024, resmetirom stands as the first and only FDA-approved DMT for non-cirrhotic MASH with moderate-to-advanced fibrosis (F2-F3), improving liver-specific lipid metabolism and indirectly reversing fibrosis.
• FGF21 Analogues: These powerfully alleviate metabolic stress in hepatocytes, showing high promise for direct anti-fibrotic effects, with multiple pipelines advancing to Phase 3.
• GLP-1 Receptor Agonists and Combinations: Based on robust weight loss, combination therapies with existing DMTs (such as THR-β agonists) remain an active area of clinical investigation and emerging hypothesis rather than an established standard.

IPF: The Rise of Novel Mechanisms

The IPF sector has entered a new phase of development, buoyed by the first novel drug approval in over a decade. See our IPF Drug Development Landscape for more info.

• PDE4 Inhibitors (e.g., Nerandomilast): FDA-approved in October 2025 for IPF and in December 2025 for PPF (brand name Jascayd®). It represents a new DMT addressing both inflammation and fibrosis, drawing significant market expectations.
• LPA1 Receptor Antagonists (e.g., BMS-986278 / Admilparant): Featuring a profile that potently inhibits fibroblast activation and migration, currently in ongoing Phase 3 trials for IPF (ALOFT-IPF, NCT06003426) and PPF.
• Inhaled Anti-fibrotic Agents: A new class delivering anti-fibrotic action directly to the lungs while minimizing systemic exposure. Nebulized treprostinil (Tyvaso) met its primary endpoint (FVC change) in both TETON-1 and TETON-2 Phase 3 trials in 2026, and an sNDA for IPF expansion is planned — note that this is a new IPF indication for an existing inhaled prostacyclin, not a reformulation of an existing anti-fibrotic drug.

High-Potential Areas for Indication Expansion: CKD and SSc

A growing strategy among pharmaceutical companies is to leverage the Proof of Concept (PoC) gained in IPF or MASH to expand into other fibrotic diseases.

1. CKD (Chronic Kidney Disease): Renal fibrosis, the end-stage of declining kidney function, is closely linked with heart failure and diabetic nephropathy. Anti-inflammatory/anti-fibrotic mechanisms successfully navigated in MASH (e.g., combination DMTs with SGLT2 inhibitors) are being repurposed for CKD.
2. SSc (Systemic Sclerosis): A severe disease where fibrosis progresses not only in the skin but across multiple organs, including the lungs (SSc-ILD). LPA1 receptor antagonists such as BMS-986278 are advancing primarily in IPF/PPF (Phase 3), while cross-indication exploration for SSc-ILD is underway in platform trials such as CONQUEST (Phase 2b) rather than dedicated late-stage SSc programs.

For pipeline trends in CKD, please see our CKD and Renal Fibrosis Landscape.

Overcoming Disease Barriers: The Pan-Fibrosis Approach

Regardless of the organ afflicted, the fundamental mechanisms of fibrosis share many common traits. Shifting target profiles from being organ-dependent to mechanism-dependent — the "Pan-fibrosis" approach — is being explored as a strategy by a growing number of companies.

• TGF-β Signaling Pathway: The "master regulator" of fibrosis. Because direct TGF-β inhibition (e.g., fresolimumab) has accumulated clinical failures, the latest DMT efforts focus on indirect modulation via integrin (αvβ6 etc.)-mediated local activation blockade and downstream-pathway control rather than systemic direct inhibition.
• Extracellular Matrix (ECM) Regulation: An approach directly targeting the enzymes responsible for producing the final fibrotic products, such as collagen.
• Macrophage Polarization Control: An immune system-based strategy aiming to normalize tissue repair processes by managing the balance between M1/M2 macrophages.

Conclusion: The Translational Imperative in the Pan-Fibrosis Era

For anti-fibrotic drugs to succeed clinically as DMTs — whether measured by surrogate marker endpoints or by demonstrable fibrosis-stage regression — appropriate preclinical model selection and a rigorous biomarker strategy designed for human trials are essential.

Pursuing a pan-fibrosis strategy in particular demands more than single-organ models: it requires a coordinated panel spanning liver (MASH), lung (IPF), kidney (CKD), and skin (SSc), together with shared readouts such as ECM-turnover markers (PRO-C3, ELF). See our Preclinical Fibrosis Model Selection Guide for a comparison of models and readouts across indications.

References & Key Sources

1. U.S. Food and Drug Administration. "FDA Approves First Treatment for Patients with Liver Scarring Due to Fatty Liver Disease." March 14, 2024. FDA News Release

2. Harrison SA, et al. A Phase 3, Randomized, Controlled Trial of Resmetirom in NASH with Liver Fibrosis. N Engl J Med. 2024;390(6):497-509. PubMed

3. Boehringer Ingelheim. "U.S. FDA approves JASCAYD® (nerandomilast) tablets for the treatment of progressive pulmonary fibrosis in adults." December 2025. BI Press Release

4. United Therapeutics Corporation. "Full Results of TETON-2 Phase 3 Clinical Trial Published in The New England Journal of Medicine." March 11, 2026. UT Investor Relations

5. Corte TJ, et al. Efficacy and Safety of Admilparant, an LPA1 Antagonist, in Idiopathic Pulmonary Fibrosis (Phase 2). Am J Respir Crit Care Med. 2025;211(2):230-238. PubMed

6. ClinicalTrials.gov. "ALOFT-IPF: A Phase 3 Study of BMS-986278 in Participants with Idiopathic Pulmonary Fibrosis." NCT06003426. ClinicalTrials.gov

7. Khanna D, et al. Design of CONQUEST, a novel Phase 2b platform clinical trial to investigate new treatments for early active systemic sclerosis with interstitial lung disease. PMC