pamrevlumab (FG-3019) / Kyntra Bio - LARVOL DELTA

Late Breaking Abstract - Discovery of an MMP7‑driven CTGF proteolytic switch as a new therapeutic intervention in IPF (ERS 2026) - "Although CTGF has long been implicated, therapeutic modulation has failed, as illustrated by the phase 3 failure of pamrevlumab. BI3810477 neutralized NTF-driven signaling, reduced fibrotic responses, and restored alveolar epithelial cell fate in patient-derived cultures, consistently outperforming earlier CTGF targeting agents. Our work explains past therapeutic failures and establishes BI3810477 as a next-generation strategy targeting a pathogenic CTGF species, providing strong rationale for phase 2 advancement."

Late-breaking abstract • Fibrosis • Idiopathic Pulmonary Fibrosis • CTGF • MMP7

Pamrevlumab plus nab-paclitaxel/gemcitabine (Pam + GA) as first- and second-line therapy in metastatic pancreatic cancer (mPDAC): Results from Precision Promise (PrP) Bayesian platform trial. (ASCO-GI 2025) - P3 | " Randomization is 70% (adaptive amongst experimental arms in stage 1) and 15%:15% amongst two control arms (GA, mFOLFIRINOX). PrP, the first Bayesian platform trial in mPDAC, performed as designed; Pam + GA did not improve OS versus GA in Line 1 and Line 2 mPDAC. The novel Bayesian design warrants further study in mPDAC to enhance efficiency of drug development. Future designs should explore different strategies to allocate patients to control arm(s) vs experimental arms and accommodate novel agents intended to benefit subsets of mPDAC."

Clinical • Metastases • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor • CTGF

Gemcitabine/nab-paclitaxel with pamrevlumab: a novel drug combination and trial design for the treatment of locally advanced pancreatic cancer. (PubMed, ESMO Open) - "Neoadjuvant chemotherapy with pamrevlumab holds promise for enhancing resection rates in patients with LAPC without added toxicity. This combination merits evaluation in a larger patient cohort."

Journal • Fibrosis • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

LAPIS: Randomized phase 3 trial of chemotherapy (CTX) with and without pamrevlumab (PAM) for locally advanced pancreatic cancer (LAPC). (ASCO-GI 2025) - P1, P1/2, P3 | "Patients received (randomized 1:1) PAM (35 mg/kg Q2W) or placebo (PBO) plus CTX (gemcitabine + nab-paclitaxel [GnP] or FOLFIRINOX [FFX] per standard protocol) for up to six 28-day cycles... LAPIS contained important LAPC trial innovations: pre/post-CTX FDG-PET imaging, objective criteria for surgical intervention, external surgical review panel, and composite EFS measurement. Addition of PAM to CTX was not associated with additional toxicity but did not improve survival outcomes for unresectable LAPC. LAPIS endpoints.CI, confidence interval; HR, hazard ratio; OR, odds ratio."

Clinical • Metastases • P3 data • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor

AI-powered therapeutic aptamer drug discovery: Targeting the CT-domain of CTGF for duchenne muscular dystrophy. (PubMed, Acta Pharm Sin B) - "While CTGF represents a therapeutic target for DMD, its VWC-domain-targeting antibody (FG-3019) failed in clinical trials...Furthermore, Apc003OA demonstrated a favorable safety profile in mdx mice. Within 10 months, we progressed from target domain discovery, aptamer drug discovery, and then obtained both Orphan Drug Designation and Pediatric Rare Disease Designation by US Food and Drug Administration."

Journal • Duchenne Muscular Dystrophy • Fibrosis • Genetic Disorders • Immunology • Muscular Dystrophy • Pediatrics • Rare Diseases • CTGF • TGFB1

Beyond attenuation: a translational review of curative-intent pharmacological targets in idiopathic pulmonary fibrosis. (PubMed, Front Med (Lausanne)) - "The current standard-of-care agents, pirfenidone and nintedanib, merely slow disease progression and are burdened by significant toxicity...Analysis reveals that targeting broad-spectrum enzymes (e.g., autotaxin via ziritaxestat) or downstream effectors (e.g., Connective Tissue Growth Factor (CTGF) via pamrevlumab) has failed, likely due to mechanistic redundancy or insufficient target engagement. In contrast, highly specific, next-generation inhibitors targeting upstream signal initiation points such as the lysophosphatidic acid receptor 1 (LPAR1) (admilparant) and local αvβ6 integrin-mediated activation of transforming growth factor-beta (TGF-β) (bexotegrast) have yielded promising Phase 2 data, demonstrating a sophisticated translational learning loop. Furthermore, the geroscience approach targeting cellular senescence (dasatinib/quercetin) has introduced a controversial new paradigm, while the recent approval of nerandomilast (a phosphodiesterase 4B (PDE4B)..."

Journal • Review • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases • CTGF • TGFB1

Comparative efficacy and safety of monotherapy and combination pharmacotherapies for idiopathic pulmonary fibrosis: a network meta-analysis of randomized controlled trials. (PubMed, BMC Pulm Med) - "RHP, rentosertib, and nintedanib showed consistent signals for preserving FVC versus placebo. However, comparative effects on progression, mortality, and safety remain uncertain due to sparse data and limited head-to-head evidence. Large, well-designed trials with harmonized endpoints and longer follow-up are needed to validate these exploratory rankings and define optimal treatment sequencing and combinations."

Journal • Monotherapy • Retrospective data • Review • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

Disrupting the CTGF–MMP7 Axis in Pulmonary Fibrosis: A Novel High-Affinity Antibody Outperforms Pamrevlumab in Patient-Derived Models (ERS LSC 2026) - "BI3810477 showed different mode of action, superior binding affinity and efficacy compared to pamrevlumab in patient-derived models, reducing myofibroblast activation and restoring alveolar cell fate. These findings establish the CTGF-MMP7 axis as a critical driver of fibrotic remodeling with implications for lung function and patient outcomes and provides a mechanistic rationale for advancing BI3810477 as a promising next-generation anti-CTGF candidate for IPF treatment."

Clinical • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases • CTGF • MMP7

Network meta-analysis of pharmacological treatments for idiopathic pulmonary fibrosis: evaluating effects on lung function. (PubMed, Front Pharmacol) - "N-acetylcysteine (NAC) combined with Roxithromycin (RXM) was the most effective intervention for improving Vital Capacity (VC) (SUCRA: 88.8%) and Forced Expiratory Volume in 1 s/Forced Vital Capacity (FEV1/FVC) (SUCRA: 97.45%). Ambroxol was the most effective intervention for improving Total Lung Capacity (TLC) (SUCRA: 82.52%), while Thalidomide was the most effective intervention for improving Diffusing Capacity of the Lung for Carbon Monoxide (DLCO) (SUCRA: 90.93%)...Additionally, future research should examine the long-term effectiveness of new drugs like Nerandomilast and Pamrevlumab, while also improving comprehensive assessments of synergistic changes across various pulmonary function indicators. https://www.crd.york.ac.uk/PROSPERO/view/CRD420251148658."

Journal • Retrospective data • Review • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases

Disrupting the CTGF-MMP7 Axis in Pulmonary Fibrosis: A Novel High-affinity Antibody Outperforms Pamrevlumab in Patient-derived Models (ATS 2026) - No abstract available

Clinical • Immunology • Pulmonary Disease • Respiratory Diseases • CTGF • MMP7

THE EFFICACY AND SAFETY OF PAMREVLUMAB IN THE MANAGEMENT OF IDIOPATHIC PULMONARY FIBROSIS: A SYSTEMATIC REVIEW (CHEST 2025) - "To date, only two drugs (Pirfenidone and Nintedanib) have been approved for management. This systematic review highlights pamrevlumab as a potential therapeutic option for IPF, with evidence demonstrating a reduction in FVC decline and disease progression, alongside a tolerable safety profile. CLINICAL IMPLICATIONS: Given the limited options, pamrevlumab presents a promising and tolerable therapeutic option for IPF management. However, more clinical trials must be conducted to evaluate its efficacy and safety relative to placebo and other approved drugs."

Clinical • Review • Cough • Fatigue • Idiopathic Pulmonary Fibrosis • Immunology • Infectious Disease • Pneumonia • Pulmonary Disease • Respiratory Diseases • CTGF

Breaking new ground in heart failure management: novel therapies and future frontiers. (PubMed, Front Cardiovasc Med) - "Emerging pharmacological therapies in heart failure management include SGLT-2 inhibitors, ARNI, Vericiguat, and Omecamtiv. Other novel therapies that are changing the scope of HF management include IV Iron therapy and new antifibrotic agents, such as pirfenidone and pamrevlumab...Additionally, the limitations and challenges associated with the emerging therapies will be discussed. Overall, this literature review aims to provide a comprehensive understanding of how these therapies are transforming the management of HF and related cardiomyopathies."

Journal • Review • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Gene Therapies • Heart Failure

Mesenchymal stem cells improve ovarian function by suppressing fibrosis through CTGF/FAK signalling in systemic lupus erythematosus. (PubMed, Lupus Sci Med) - "This study demonstrated that UC-MSC treatment ameliorated ovarian dysfunction and attenuated ovarian fibrosis in lupus mice by modulating the CTGF/FAK-Tyr576/577 phosphorylation pathway."

Journal • Fibrosis • Immunology • Inflammation • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus • Transplantation • CD4 • CTGF • ER • IL1B • TNFA

New Challenging Systemic Therapies for Juvenile Scleroderma: A Comprehensive Review. (PubMed, Pharmaceuticals (Basel)) - " Biologic agents such as tocilizumab, rituximab, and abatacept, along with small molecules including Janus kinase (JAK) inhibitors and imatinib, have demonstrated potential in managing refractory cases by reducing skin fibrosis and pulmonary involvement. Novel approaches-such as pamrevlumab, nintedanib, and chimeric antigen receptor (CAR-T) cell therapy-target fibrotic and autoimmune pathways but remain investigational in children... While innovative systemic therapies show promise for juvenile scleroderma, their widespread clinical application remains limited by insufficient pediatric-specific evidence. Large, multicenter, long-term trials are urgently needed to establish safety, efficacy, and optimal treatment algorithms that are tailored to the pediatric population."

Journal • Review • Fibrosis • Immunology • Pediatrics • Scleroderma • Systemic Sclerosis • Transplantation

AI-powered therapeutic aptamer drug discovery:Targeting CTGF CT-domain for Duchenne muscular dystrophy (ASGCT 2025) - "Importantly, this aptamer demonstrated better fibrosis inhibitory activity in vitro and in mdx mice when compared to the FG-3019, with no detected lesions in the major organs. Within 10 months, we went from target domain discovery, aptamer drug discovery, and then obtained the orphan drug (DRU-2024-10138) and pediatric rare disease designation (RPD-2024-838) by US FDA."

Duchenne Muscular Dystrophy • Fibrosis • Genetic Disorders • Immunology • Muscular Dystrophy • Pediatrics • Rare Diseases • CTGF

Minimum clinically important difference in Quantitative Lung Fibrosis score associated with all-cause mortality in idiopathic pulmonary fibrosis: subanalysis from two phase II trials of pamrevlumab. (PubMed, BMJ Open) - P2 | "A conservative metric of 2% can be used as the MCID of QLF for predicting all-cause mortality. This may be considered in IPF trials in which the degree of structural fibrosis assessed via HRCT is an endpoint. The MCID of SGRQ and FVC corresponds with a greater amount of QLF and may reflect that a greater amount of change in fibrosis is required before there is functional change."

Journal • P2 data • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases • CTGF

"Regression to the truth": lessons learned from negative IPF trials. (PubMed, Breathe (Sheff)) - "Despite the approval of pirfenidone and nintedanib that slow disease progression, IPF remains a disease with poor survival...We examine three pivotal trials of novel IPF therapies, zinpentraxin alfa, ziritaxestat and pamrevlumab, that failed in late-stage clinical development...Negative trials are not failures but opportunities for learning. By recognising and addressing these challenges, while also embracing novel trial methodologies, we can enhance drug development and improve IPF outcomes."

Journal • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

Precision Promise: A Multi-center Trial to Evaluate Multiple Regimens in Metastatic Pancreatic Cancer (clinicaltrials.gov) - P3 | N=502 | Completed | Sponsor: Pancreatic Cancer Action Network | Active, not recruiting ➔ Completed | N=825 ➔ 502 | Trial completion date: Jun 2027 ➔ Feb 2025 | Trial primary completion date: Jun 2027 ➔ Feb 2025

Enrollment change • Trial completion • Trial completion date • Trial primary completion date • Hepatology • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

The latest developments in synthetic approaches to duchenne muscular dystrophy. (PubMed, Expert Rev Neurother) - "Although corticosteroids remain the standard treatment, newly approved drugs such as exon-skipping therapies, vamorolone, delandistrogene moxeparvovec, and givinostat provide new treatment options...The accelerated FDA review process has enabled faster approval of new medications; however many have provided minimal clinical benefit to patients. Despite these challenges, continued drug development and innovative research offer hope to patients."

Journal • Review • Cardiomyopathy • Cardiovascular • Duchenne Muscular Dystrophy • Fibrosis • Gene Therapies • Genetic Disorders • Immunology • Muscular Dystrophy • Respiratory Diseases

Dr Oberstein on Data for Pamrevlumab Plus Nab-Paclitaxel/Gemcitabine in PDAC (OncLive) - P2/3 | N=825 | NCT04229004 | "Results presented at the 2025 Gastrointestinal Cancers Symposium showed no improvement in progression-free survival (PFS) or overall survival (OS) with the addition of pamrevlumab. In the first-line cohort, median PFS was 5.3 months with concurrent nab-paclitaxel/gemcitabine (n = 23) and 5.9 months with pamrevlumab plus chemotherapy (n = 102; HR, 0.64; 95% CI, 0.36-1.14). Confirmed objective response rates (ORR) were 26.1% in the concurrent nab-paclitaxel/gemcitabine arm and 35.3% in the pamrevlumab combination arm. In the second-line setting, median PFS was 7.0 months with chemotherapy alone (n = 22) and 3.9 months with pamrevlumab plus nab-paclitaxel/gemcitabine (n = 111; HR, 1.35; 95% CI, 0.78-2.33). The ORRs were 4.5% and 9.0%, respectively."

P2/3 data • Pancreatic Ductal Adenocarcinoma

Pamrevlumab Plus Chemo Fails to Improve Survival in Unresectable Locally Advanced Pancreatic Cancer (OncLive) - P3 | N=284 | LAPIS (NCT03941093) | Sponsor: FibroGen | "The addition of pamrevlumab to chemotherapy failed to demonstrate a survival benefit but was associated with an acceptable safety profile in patients with unresectable locally advanced pancreatic cancer (LAPC), according to findings from the phase 3 LAPIS trial (NCT03941093) presented at the 2025 Gastrointestinal Cancers Symposium. Topline results in the combination arm included a median overall survival (OS) of 17.3 months compared with 18.0 months in the placebo arm (HR, 1.08; 95% CI, 0.83-1.41; P = .5487). The median EFS was 5.7 months in the combination arm and 5.8 months in the placebo arm (HR, 1.05; 95% CI, 0.78-1.39). Additional efficacy data included a median progression-free survival (PFS) of 9.4 months in the pamrevlumab plus chemotherapy arm and 9.4 months in the placebo arm (HR, 1.01; 95% CI, 0.65-1.56)."

P3 data • Pancreatic Cancer

The case of Connective Tissue Growth Factor and the pit of misleading and improper nomenclatures. (PubMed, J Cell Commun Signal) - No abstract available

Journal • Immunology • CTGF

ER stress-induced YAP upregulation leads to chondrocyte phenotype loss in age-related osteoarthritis. (PubMed, Front Pharmacol) - "Pamrevlumab effectively prevents this phenotype loss in YAPOE mice, suggesting its potential as a therapeutic agent for OA. These findings provide new insights into the molecular mechanisms of OA and highlight the importance of targeting the ER stress-YAP-CTGF signaling pathway in OA treatment and prevention."

Journal • Immunology • Osteoarthritis • Pain • Rheumatology • CTGF • ER

LAPIS: Evaluation of Efficacy and Safety of Neoadjuvant Treatment With Pamrevlumab in Combination With Chemotherapy (Either Gemcitabine Plus Nab-paclitaxel or FOLFIRINOX) in Participants With Locally Advanced Pancreatic Cancer (clinicaltrials.gov) - P3 | N=284 | Completed | Sponsor: FibroGen | Active, not recruiting ➔ Completed

Combination therapy • Metastases • Trial completion • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

Evidence from recent clinical trials in fibrotic interstitial lung diseases. (PubMed, Curr Opin Pulm Med) - "Despite recent frustrating negative results, there is a growing portfolio of candidate drugs developed in both IPF and PPF."

Journal • Review • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases • CTGF