SSc Drug Landscape 2026: Pipeline & New Frontiers

Introduction

Systemic sclerosis (SSc) is an autoimmune disease characterized by progressive fibrosis of the skin and internal organs, accompanied by vasculopathy. Among connective tissue diseases, SSc carries the highest mortality rate, with particularly poor prognosis when complicated by interstitial lung disease (ILD) or pulmonary arterial hypertension (PAH).

For decades, SSc was regarded as a condition with "no effective treatment." However, the approval of nintedanib for SSc-ILD in 2019 marked a turning point, and treatment options have expanded rapidly throughout the 2020s. Following tocilizumab's approval targeting the immune-inflammatory pathway, a mix of SSc-specific programs (CABA-201 CD19 CAR-T, Romilkimab) and adjacent immune/fibrosis assets advancing in IBD/DM/IPF/PPF has made the field strategically active, transforming SSc drug development from a "barren landscape" into one of the most active areas in fibrosis research.

This article examines the current state and emerging business opportunities in SSc therapeutics through three lenses: the approved drug market, the competitive pipeline landscape, and preclinical model selection strategies.

1. Epidemiology and Market Size

1.1 Patient Population and Disease Burden

SSc prevalence varies by region, with estimates of approximately 25–30 per 100,000 in the United States and 10–20 per 100,000 in Europe. The global patient population is estimated at approximately 2.5 million, with roughly 30–40% developing ILD.

Key epidemiological features of SSc include:

• Sex ratio: Women are affected approximately 4–5 times more frequently than men
• Age of onset: Peak incidence in the 30s–50s
• Subtypes: Broadly classified into diffuse cutaneous SSc (dcSSc) and limited cutaneous SSc (lcSSc)
• Causes of death: ILD and PAH account for approximately 60% of all-cause mortality

1.2 Market Size Projections

The global SSc therapeutics market sits within the rare disease category (approximately 2.5 million patients worldwide) and, when PAH therapies (bosentan, riociguat, etc.) and ILD therapies (nintedanib) indicated for SSc are included, is on a multi-billion-dollar scale. Specific dollar estimates vary significantly across market research firms depending on whether PAH agents and which geographies are included, so we avoid a specific dollar figure here. Future growth is expected to be driven by three key factors:

1. Expansion of SSc-ILD therapies: New drug approvals following nintedanib will broaden the addressable patient population
2. Emergence of disease-modifying therapies (DMTs): Growing expectations for agents that correct the underlying immune dysregulation, not merely slow fibrosis progression
3. Advances in biomarker development: Earlier diagnosis and improved patient stratification are shifting the window for therapeutic intervention forward

2. Approved Therapies: The Current Treatment Landscape

2.1 Overview of Approved Agents

The number of regulatory-approved drugs for SSc remains limited, but significant progress has been made since 2019.

Brand Name	Generic Name	Company	Approval / Indication	Mechanism of Action
Ofev	Nintedanib	Boehringer Ingelheim	2019 FDA approval (SSc-ILD)	Multi-kinase inhibitor (VEGFR/FGFR/PDGFR)
Actemra	Tocilizumab	Roche / Chugai	2021 FDA approval (SSc-ILD)	Anti-IL-6 receptor antibody
Off-label use	Mycophenolate mofetil (MMF)	—	Not approved (guideline-recommended)	Immunosuppressant (IMPDH inhibitor)
Off-label use	Methotrexate (MTX)	—	Not approved (guideline-recommended)	Immunosuppressant (folate antagonist)
PAH indication	Bosentan / Riociguat	Actelion / Bayer	Used for SSc-PAH	ERA / sGC stimulator

2.2 Nintedanib: Standard of Care for SSc-ILD

Boehringer Ingelheim's nintedanib demonstrated a 44% reduction in the annual rate of FVC (forced vital capacity) decline compared to placebo in the SENSCIS trial (Phase 3, n=576) in SSc-ILD patients (−52.4 mL/year vs. −93.3 mL/year). This represented a successful translation of evidence established in IPF to the SSc-ILD setting, and nintedanib is a widely used approved therapeutic option for SSc-ILD (actual selection depends on ILD progression, inflammatory activity, concomitant immunosuppression, and tolerability).

However, nintedanib has clear limitations:

• Limited efficacy on skin fibrosis: No improvement in mRSS (modified Rodnan Skin Score) has been demonstrated
• Gastrointestinal adverse effects: Diarrhea occurs in approximately 75% of patients, sometimes necessitating dose adjustment or discontinuation
• Slows progression rather than reverses it: The drug decelerates fibrosis progression but has not demonstrated reversibility

2.3 Tocilizumab: An Approved Therapy Targeting the Immune Pathway

Roche's tocilizumab received FDA approval for SSc-ILD in 2021, based on the focuSSced trial (Phase 3, n=212). Although the primary endpoint (change in mRSS at 48 weeks) did not reach statistical significance, the significant preservation of FVC as a secondary endpoint was pivotal in securing approval.

IL-6 is implicated in virtually every aspect of SSc pathogenesis—inflammation, fibroblast activation, and vascular endothelial damage. Tocilizumab is therefore a landmark therapy, providing clinical proof-of-concept for an immune-targeted approach in SSc.

3. Development Pipeline: SSc-Specific Trials & Adjacent / Reference Assets

3.1 Pipeline Overview

The SSc pipeline in the late 2020s features a mix of SSc-specific programs (CABA-201, Romilkimab) alongside adjacent-indication candidates (in IBD/DM/IPF/PPF) and mechanism-of-interest reference assets (TYK2-selective, anti-FcRn, etc.). The table below mixes SSc-dedicated trials, adjacent-indication expansion candidates, and pathway-reference entries — distinguished in the "Primary Target Indication" column.

Candidate	Company	Mechanism of Action	Phase	Primary Target Indication	NCT Number
Duvakitug (TEV-48574)	Teva / Sanofi co-development	Anti-TL1A antibody	Phase 3 (UC/CD ongoing, Sanofi 2026-02-17)	IBD (UC/CD; Phase 3 ongoing per Sanofi 2026-02-17). No SSc program disclosed.	NCT05499130
CABA-201 (rese-cel)	Cabaletta Bio	CD19 CAR-T (4-1BB co-stim, FDA RMAT)	Phase 1/2 (RESET-SSc; complete data anticipated H1 2026)	dcSSc / myositis	NCT06328777 / RESET-SSc program
Brepocitinib	Priovant / Roivant	TYK2 / JAK1 dual inhibitor	DM Phase 3 completed (VALOR positive)	DM (VALOR Phase 3 positive, PDUFA Q3 2026). SSc not disclosed on Priovant pipeline; pathway reference only	NCT05437263 (VALOR-DM)
Itepekimab	Sanofi / Regeneron	Anti-IL-33 antibody	Phase 2 (COPD / asthma)	No SSc-ILD trial registered on ClinicalTrials.gov (IL-33 pathway reference entry)	—
BMS-986278 (Admilparant)	Bristol-Myers Squibb	LPAR1 antagonist	Phase 2 (IPF/PPF) / Phase 3 ALOFT-IPF & ALOFT-PPF	IPF / PPF lead; PPF cohort may include SSc-ILD as underlying condition (potential future expansion; no BMS-disclosed SSc-ILD-dedicated trial)	NCT06003426 (ALOFT-IPF) / NCT06025578 (ALOFT-PPF)
Deucravacitinib	Bristol-Myers Squibb	TYK2 inhibitor	Mechanism reference only	Approved for psoriasis (Sotyktu). No SSc trial registered on ClinicalTrials.gov; included as TYK2-selective inhibition reference entry	—
Nipocalimab	Johnson & Johnson	Anti-FcRn antibody	Phase 2/3 (gMG leads)	No SSc trial registered on ClinicalTrials.gov; internal exploratory / FcRn-blockade reference entry	—
Romilkimab	Sanofi	Anti-IL-4/IL-13 bispecific antibody	Phase 2 completed (Allanore 2020, Ann Rheum Dis 79(12):1600-1607)	dcSSc	NCT02921971 / PMID 32963047

3.2 Detailed Analysis of Key Candidates

Anti-TL1A Antibody: Duvakitug (Teva / Sanofi)

TL1A (TNF-like ligand 1A) is expressed on T cells, ILCs, and macrophages, and signals through DR3 to drive mucosal inflammation and fibrotic remodeling. Duvakitug (TEV-48574) is a Teva-owned anti-TL1A antibody that entered a global co-development and commercialization agreement with Sanofi in October 2024 (~$500M upfront; Sanofi leads ex-US, Teva/Sanofi co-commercialize in US). Its lead indications are inflammatory bowel disease (ulcerative colitis and Crohn's disease); no dedicated SSc-ILD program has been publicly disclosed.

Because TL1A signaling engages both immune-cell activation and fibroblast activation, adjacent pan-fibrotic expansion is under discussion, though SSc-ILD clinical evidence remains limited. It is listed here as a reference asset relevant to pan-fibrosis strategy. A related anti-TL1A antibody, Tulisokibart (PRA023), which Merck acquired through its 2023 purchase of Prometheus Biosciences, is separately in IBD development.

CD19 CAR-T: CABA-201 / rese-cel (Cabaletta Bio)

The most attention-grabbing development in 2024-2026 has been CAR-T therapy for autoimmune disease. Cabaletta Bio's CABA-201 (rese-cel) is a CD19-directed, 4-1BB co-stimulated fully human CAR-T (single-target, BCMA is not part of the construct; see Cabaletta pipeline). Initial data from the RESET-SSc Phase 1/2 trial (NCT06328777) in dcSSc have now been disclosed. At ACR Convergence 2025 (October 27, 2025), Cabaletta presented interim data on an SSc cohort of n=6 (3 SSc-Skin + 3 SSc-Organ), with all 4 patients with ≥3 months of follow-up achieving an rCRISS-25 response off all immunomodulators and steroids. Safety was manageable: low-grade CRS (Grade 1-2) in 3/6 and one Grade 3 ICANS event (previously reported in March 2025). FDA has granted Regenerative Medicine Advanced Therapy (RMAT) designation to rese-cel for SSc, with registrational cohort design alignment anticipated in H1 2026. Complete RESET-SSc Phase 1/2 cohort data are scheduled for presentation at EULAR 2026 on June 4, 2026 (Cabaletta-sponsored satellite symposium, 5:30 PM BST), advancing the disease-modifying therapy (DMT) via deep B-cell depletion paradigm toward clinical substantiation.

TYK2/JAK1 Dual Inhibitor: Brepocitinib (Priovant / Roivant)

Brepocitinib is an oral small molecule that inhibits both TYK2 and JAK1 simultaneously, developed by Priovant Therapeutics (a Pfizer/Roivant joint venture). VALOR Phase 3 (NCT05437263) is a dermatomyositis (DM) trial, not an SSc trial. Priovant announced positive DM topline (TIS 46.5 vs 31.2, p=0.0006, n=241) in September 2025, and the NDA is filed with a PDUFA target in Q3 2026. For SSc (dcSSc), Brepocitinib is not disclosed on Priovant's public pipeline (which lists DM, NIU, LPP, and CS), and no SSc Phase 2/3 is registered at this time. It is included here as a reference case for considering how TYK2/JAK1 inhibition might extend into autoimmune fibrotic conditions, based on its DM success.

Anti-IL-33 Antibody: Itepekimab (Sanofi / Regeneron)

IL-33 is an alarmin released in response to tissue damage that triggers type 2 immune responses. Elevated IL-33 levels have been reported in the early stages of skin and lung fibrosis in SSc, raising expectations that targeting this upstream alarmin could provide more fundamental disease control.

Sanofi has built extensive expertise in the type 2 inflammation space through Dupilumab (anti-IL-4Rα antibody), and Itepekimab represents a natural extension of that knowledge base. However, Sanofi/Regeneron is developing Itepekimab in COPD (AERIFY-1/2) and asthma; no SSc-ILD trial is registered on ClinicalTrials.gov. This entry is included as a pathway-level reference, not an active SSc program.

LPAR1 Antagonist: BMS-986278 / Admilparant (Bristol-Myers Squibb)

Lysophosphatidic acid receptor type 1 (LPAR1) mediates signaling that promotes fibroblast activation and differentiation into myofibroblasts. BMS-986278 (INN: Admilparant) was studied in a Phase 2 trial covering IPF and PPF cohorts (NCT04308681; Corte TJ et al., Am J Respir Crit Care Med 2025;211:230-238, PMID 39393084). The IPF 60 mg arm showed a 26-week FVC change of −1.2% vs −2.7% for placebo (between-group difference non-significant); the PPF cohort reached a 3.2 percentage-point absolute difference (95% CI 0.7–5.7). Phase 3 ALOFT-IPF (NCT06003426, primary completion Oct 2026) and ALOFT-PPF (NCT06025578) are underway. Because the ALOFT-PPF PPF cohort may include SSc-ILD as an underlying condition, BMS-986278 is a potential future expansion candidate (no BMS-disclosed SSc-ILD-dedicated trial at this time).

Because LPAR1 antagonists operate through a mechanism distinct from existing antifibrotic agents (nintedanib, pirfenidone), they are attracting considerable interest as potential combination therapy partners.

TYK2 Inhibitor: Deucravacitinib (BMS)

Deucravacitinib is an oral agent that selectively inhibits TYK2 within the JAK family and is already approved for psoriasis (as Sotyktu). TYK2 is involved in IFN-I/IL-12/IL-23 signaling, broadly covering pathways implicated in SSc immune dysregulation. Compared to conventional JAK1/2 inhibitors, it offers a different immunosuppressive profile, with expectations of a reduced infection risk. However, no SSc clinical trial is registered on ClinicalTrials.gov; this entry is included as a TYK2-selective inhibition reference for SSc-pathway discussion only.

Anti-FcRn Antibody: Nipocalimab (Johnson & Johnson)

Nipocalimab inhibits the neonatal Fc receptor (FcRn), accelerating the degradation of IgG autoantibodies—a novel mechanism of action. Given that autoantibodies such as anti-topoisomerase I (anti-Scl-70) and anti-centromere antibodies play a role in SSc pathogenesis, directly reducing autoantibody levels represents a scientifically rational approach. However, J&J's disclosed pipeline does not register a Nipocalimab SSc-ILD trial on ClinicalTrials.gov; the program remains at internal exploratory stage. Progress in lead indications (generalized myasthenia gravis Phase 3 Vivacity-MG3, hemolytic disease of fetus and newborn) will likely inform the SSc expansion decision.

3.3 Discontinued or Setback Candidates

Not every candidate has progressed smoothly. Several notable programs have been discontinued or encountered setbacks:

• Lenabasum (Corbus Pharmaceuticals): A cannabinoid receptor CB2 agonist. The Phase 3 RESOLVE-1 trial failed to demonstrate a statistically significant improvement in ACR CRISS / mRSS over placebo (Spiera R, Arthritis Rheumatol 2023;75(9):1608-1618, PMID 37098795). This outcome underscored the inherent difficulty of conducting clinical trials in SSc.
• Abituzumab (EMD Serono / Merck KGaA): An anti-αv integrin antibody. A Phase 2 trial in SSc-ILD (NCT02745145, Terminated) failed to demonstrate meaningful changes in secondary endpoints, and development was deprioritized.
• Rilonacept (Kiniksa / Regeneron): An IL-1α/β inhibitor. A Phase 1/2 trial (NCT01538719, Completed) targeting SSc-related calcinosis failed to meet expectations.

These setbacks highlight the persistent challenges in SSc clinical trial design—patient heterogeneity, high placebo response rates, and limitations of current outcome measures.

4. Preclinical Model Selection: Animal Models Supporting SSc Drug Discovery

Preclinical evaluation of SSc therapeutics requires selecting animal models that appropriately reflect the multifaceted disease pathology—immune dysregulation, fibrosis, and vasculopathy. The following table compares the major models.

4.1 Comparison of Major Models

Model	Induction Method	Pathology Reproduced	Study Duration	Key Endpoints	Strengths	Limitations
Bleomycin dermal fibrosis	Repeated subcutaneous bleomycin injections (3–4 weeks)	Skin fibrosis, inflammation	4–6 weeks	Dermal thickness, collagen content, hydroxyproline	High reproducibility, short duration, low cost	Poor reproduction of vasculopathy, spontaneous resolution
HOCl-induced model	Repeated subcutaneous HOCl injections	Skin fibrosis, vasculopathy, autoantibody production	6–8 weeks	Dermal thickness, collagen, anti-topoisomerase I antibodies	Reproduces multifaceted SSc pathology	Technically challenging, variable results
Tsk1 mouse	Genetic modification (Fbn1 gene duplication)	Skin thickening (hypodermal), pulmonary emphysema	Spontaneous onset	Dermal thickness, hydroxyproline	Genetically stable model	Lacks inflammatory component, pathology differs from true SSc
Tsk2 mouse	Spontaneous mutation	Skin fibrosis, inflammation	Spontaneous onset	Dermal thickness, collagen	More inflammation than Tsk1	Difficult to breed, limited availability
Fra-2 transgenic	Fra-2 overexpression	Skin/lung fibrosis, vasculopathy	Spontaneous onset	Dermal thickness, lung fibrosis score, vascular remodeling	Reproduces skin, lung, and vascular components	Requires specialized colony management

4.2 Key Considerations for Model Selection

Model selection should be guided by the candidate drug's mechanism of action and the pathological components being evaluated.

• Drugs targeting immune/inflammatory pathways (anti-IL-33, anti-IL-4/IL-13, TYK2 inhibitors, etc.): The HOCl model or the early phase of the bleomycin model is well-suited. These models reproduce the inflammation-to-fibrosis cascade, making it easier to detect the effects of immunomodulatory agents.

• Direct antifibrotic agents (LPAR1 antagonists, anti-integrin antibodies, etc.): The late-phase bleomycin model or Tsk1 mouse are suitable candidates for evaluating efficacy against established fibrosis.

• Evaluating effects on vasculopathy: The HOCl model or Fra-2 transgenic mouse is optimal, enabling assessment of capillary loss and vascular remodeling.

• Assessing lung fibrosis (SSc-ILD): The bleomycin intratracheal instillation model is the most widely used, though the Fra-2 mouse also develops spontaneous pulmonary fibrosis.

4.3 Trends in Evaluation Endpoints

Several emerging endpoints are gaining traction in SSc preclinical evaluation:

• Single-cell RNA-seq: High-resolution assessment of fibroblast subpopulation shifts (myofibroblasts, lipofibroblasts, etc.)
• Micro-CT: Non-invasive longitudinal evaluation of dermal thickness and pulmonary architecture
• Digital pathology: AI-assisted standardization and improved reproducibility of fibrosis scoring
• Serum biomarker panels: Pharmacodynamic monitoring through quantification of COMP, CCL2, IL-6, and other markers

5. The CRO Business Perspective: Outsourcing Demand in the SSc Space

5.1 Demand Drivers

Demand for preclinical study outsourcing in SSc is expanding due to several structural factors:

High technical expertise barrier: SSc animal models are operationally more demanding than IPF or NASH models. The HOCl model and Fra-2 transgenic mouse, in particular, require specialized know-how. As a result, pharmaceutical companies are increasingly opting to outsource these studies to CROs rather than conducting them in-house.

Pipeline growth driving demand: As discussed above, multiple candidates have advanced to Phase 2 and beyond in SSc, with each development program generating demand for additional preclinical studies (mechanism validation, biomarker exploration).

Increasing complexity of combination studies: Growing demand for evaluation in combination with nintedanib or MMF is adding trial design complexity, further incentivizing CRO outsourcing.

5.2 Competitive Landscape

A brief overview of the CRO competitive landscape for SSc preclinical models reveals the following segmentation:

• Large CROs (Charles River, Covance/Labcorp, etc.): Capable of running standard bleomycin models at scale, but may lack deep SSc-specific expertise
• Fibrosis-specialized CROs: Differentiated by in-depth knowledge of skin and lung fibrosis models with proprietary endpoint assessment capabilities
• Academic-CRO partnerships: Provide access to genetically modified mice and humanized models through collaborations with university SSc research laboratories

5.3 Differentiation Strategies

Key differentiators for CROs seeking to establish a competitive position in the SSc space include:

1. Multi-model parallel execution: The ability to run bleomycin, HOCl, and genetically modified models at a single facility for comparative evaluation
2. Advanced endpoint assessment: Standard integration of digital pathology, single-cell RNA-seq, Micro-CT, and other cutting-edge technologies
3. Translational bridging: Expertise in correlating preclinical data with clinical biomarkers
4. Integrated skin-lung-vascular evaluation: Protocols enabling comprehensive assessment of SSc's multifaceted pathology within a single study

6. Key Developments to Watch (2026–2028)

6.1 Critical Clinical Milestones

1. CABA-201 RESET-SSc Phase 1/2 complete readout (EULAR 2026, June 4, 2026): Interim SSc cohort data (n=6; 4/4 with ≥3 months of follow-up achieved rCRISS-25 off all immunomodulators) were presented at ACR Convergence 2025. Cabaletta's Q1 2026 update confirmed that complete Phase 1/2 cohort data will be presented at a Cabaletta-sponsored satellite symposium at EULAR 2026 (5:30 PM BST, June 4, 2026). The complete readout will test whether the disease-modifying effect of a CD19 CAR-T in dcSSc (deep B-cell depletion → autoantibody clearance → skin/organ fibrosis improvement) persists — the most consequential data point that could reshape the SSc treatment paradigm. FDA RMAT designation is in place, with registrational cohort design alignment also targeted for H1 2026.
2. Brepocitinib VALOR (DM) approval and potential SSc expansion: VALOR Phase 3 is in dermatomyositis (positive topline Sep 2025, PDUFA Q3 2026). If Priovant subsequently initiates SSc (dcSSc) Phase 2/3, TYK2/JAK1 dual inhibition could become the first oral DMT candidate in SSc.
3. Duvakitug (anti-TL1A) pan-fibrosis expansion: Whether TL1A inhibition — currently in IBD Phase 2b (RELIEVE UCCD) — ultimately extends into SSc-ILD will be a bellwether for the pan-fibrosis thesis.
4. Admilparant / BMS-986278 ALOFT-IPF / ALOFT-PPF readouts: Success of Phase 3 in IPF/PPF would set up a dedicated SSc-ILD trial launch (not yet disclosed by BMS). Phase 2 showed a 3.2 pp absolute FVC difference in the PPF cohort but a non-significant result in IPF.
5. SSc-expansion potential for TYK2-selective inhibition: How TYK2-selective inhibitors (such as Deucravacitinib, approved for psoriasis but with no SSc trial registered) might expand into SSc will be a key test of the selective JAK-inhibition strategy.

6.2 Market-Shaping Trends

• Clinical implementation of biomarker stratification: Incorporating skin gene expression profiles (inflammatory-dominant vs. fibrotic-dominant) into clinical trial design for patient selection could significantly improve success rates. The lessons learned from the Lenabasum failure—that drug efficacy is diluted in heterogeneous patient populations—are being put into practice.
• Focus beyond ILD and PAH: Therapeutic development is beginning to address organ complications that have long been categorized as "unmet needs," including SSc-related digital ulcers, gastrointestinal involvement, and myocardial fibrosis.
• Pan-fibrosis approach: The strategy of expanding antifibrotic agents developed for IPF or NASH into SSc-ILD is accelerating. Following the precedent set by nintedanib's successful transition from IPF to SSc-ILD, LPAR1 antagonists and αvβ6 integrin inhibitors are pursuing similar cross-indication strategies.

7. Summary and Outlook

The SSc treatment landscape underwent a major inflection around 2025 and has moved into an "execution phase" in 2026, with the CD19 CAR-T CABA-201 disclosing interim SSc data, TYK2/JAK1 inhibition (brepocitinib) advancing through PDUFA in the adjacent dermatomyositis indication, and anti-TL1A antibody (duvakitug) testing the pan-fibrosis expansion thesis. Nintedanib and tocilizumab—the two approved therapies—have expanded recognition of SSc as a "treatable disease," and with multiple candidates spanning diverse mechanisms now in Phase 1-3, this period truly represents a "renaissance" in SSc drug discovery.

At the same time, the failure of lenabasum has demonstrated that the challenges of SSc clinical trials remain formidable. Overcoming patient heterogeneity, long trial durations, and placebo effects will require robust biomarker-based patient stratification and rigorous preclinical model validation.

When selecting preclinical models, matching the model to the candidate drug's mechanism of action is often the difference between success and failure. The versatility of the bleomycin dermal fibrosis model, the multifaceted pathology reproduced by the HOCl model, and the stability of genetically modified mice—understanding and appropriately combining the strengths of each model is essential.

If you are navigating disease model selection or preclinical study design, we are happy to help. We can support you in selecting the optimal model based on the latest insights in the SSc field.

References and Clinical Trial Information

Approved Drug Clinical Trials

1. Distler O, et al. Nintedanib for Systemic Sclerosis-Associated Interstitial Lung Disease. N Engl J Med. 2019;380(26):2518-2528. PMID 31112379 (SENSCIS: NCT02597933)

2. Khanna D, et al. Tocilizumab in systemic sclerosis: a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Respir Med. 2020;8(10):963-974. PMID 32866440 (focuSSced: NCT02453256)

Development Pipeline (Phase 1-3)

3. Duvakitug / TEV-48574 (anti-TL1A antibody, Teva/Sanofi) IBD (UC/CD) RELIEVE UCCD induction Phase 2b: NCT05499130 / LTE maintenance Phase 2b: NCT05668013 (source of the 44-week durable efficacy data). Sanofi 2026-02-17 press release reports 44-week Phase 2b LTE durable efficacy and confirms Phase 3 ongoing in UC and CD (https://www.sanofi.com/en/media-room/press-releases/2026/2026-02-17-11-00-00-3239014/). Teva-Sanofi co-development agreement (Oct 2024; ~$500M upfront + up to $1B in milestones) / Teva-Blackstone Life Sciences strategic growth capital agreement (2026, $400M) to accelerate Phase 3 (Teva IR 2026).

4. CABA-201 / rese-cel (CD19 CAR-T, 4-1BB co-stim, Cabaletta Bio) RESET-SSc Phase 1/2: NCT06328777. At ACR Convergence 2025 (Oct 27, 2025), Cabaletta presented interim SSc cohort data (n=6); 4/4 patients with ≥3 months of follow-up achieved an rCRISS-25 response off all immunomodulators and steroids (Cabaletta PR 2025-10-27). FDA RMAT designation granted for SSc. Complete Phase 1/2 cohort data scheduled for presentation at EULAR 2026 (Cabaletta-sponsored satellite symposium, June 4, 2026, 5:30 PM BST). Cabaletta Pipeline

5. Brepocitinib (TYK2/JAK1 inhibitor, Priovant/Roivant) VALOR Phase 3 is a dermatomyositis (DM) trial (NCT05437263, positive topline Sep 2025, TIS 46.5 vs 31.2, p=0.0006, n=241; NDA filed, PDUFA Q3 2026). SSc is not disclosed on Priovant's public pipeline (which lists DM/NIU/LPP/CS).

6. Admilparant / BMS-986278 (LPAR1 antagonist, BMS) Phase 2 IPF/PPF: Corte TJ, et al. Am J Respir Crit Care Med 2025;211:230-238. PMID 39393084 / ALOFT-IPF Phase 3: NCT06003426 / ALOFT-PPF Phase 3: NCT06025578

7. Deucravacitinib (TYK2 inhibitor, BMS) approved for psoriasis (Sotyktu). No SSc clinical trial registered; included as a TYK2-selective inhibition mechanism reference.

8. Nipocalimab (anti-FcRn, J&J) leads in gMG (Phase 3 Vivacity-MG3) and HDFN. No SSc clinical trial registered; included as an FcRn-blockade mechanism reference.

Discontinued / Failed Candidates

9. Spiera R, et al. Efficacy and Safety of Lenabasum, a Cannabinoid Type 2 Receptor Agonist, in a Phase 3 Randomized Trial in Diffuse Cutaneous Systemic Sclerosis. Arthritis Rheumatol. 2023;75(9):1608-1618. PMID 37098795 (RESOLVE-1: NCT03398837)

Preclinical Model Reviews

10. Marangoni RG, et al. Animal models of scleroderma: recent progress. Curr Opin Rheumatol. 2016;28(6):561-70. PMID 27533324 (DOI 10.1097/BOR.0000000000000331)

11. Avouac J, et al. Mouse model of experimental dermal fibrosis: the bleomycin-induced dermal fibrosis. Methods Mol Biol. 2014;1142:91-8. PMID 24706279 (DOI 10.1007/978-1-4939-0404-4_11)

12. Servettaz A, et al. Selective oxidation of DNA topoisomerase 1 induces systemic sclerosis in the mouse. J Immunol. 2009;182(9):5855-64. PMID 19380834 (DOI 10.4049/jimmunol.0803705)

Market Analysis

13. GlobalData. Systemic Sclerosis: Global Drug Forecast and Market Analysis. 2024.

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