pamrevlumab (FG-3019) / FibroGen - LARVOL DELTA

"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 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

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

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

FibroGen Announces Topline Results from Two Late-Stage Pamrevlumab Pancreatic Cancer Studies and Provides Corporate Update (GlobeNewswire) - P3 | N=284 | LAPIS (NCT03941093) | Sponsor: FibroGen | P2/3 | N=825 | Precision Promise (NCT04229004) | "The pamrevlumab experimental arm in PanCAN’s Precision Promise Phase 2/3 adaptive platform trial compared treatment with pamrevlumab...for treatment in first line (1L) and second line (2L) patients with metastatic pancreatic ductal adenocarcinoma (mPDAC). The pamrevlumab arm of the study did not meet the primary endpoint of overall survival as determined by the protocol pre-specified Bayesian statistical analysis. The Phase 3 LAPIS trial compared treatment with pamrevlumab...for the treatment of locally advanced, unresectable pancreatic cancer (LAPC). The study did not meet the primary endpoint of overall survival.....The pamrevlumab development program will be terminated and the Company plans to expeditiously wind down any remaining pamrevlumab obligations."

Discontinued • P2/3 data • P3 data • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma

The future of clinical trials in idiopathic pulmonary fibrosis. (PubMed, Curr Opin Pulm Med) - "Advances in study design, end point selection and statistical analysis, and innovative strategies for more efficient enrolment of study participants have the potential to increase the likelihood of success of late-phase clinical trials in IPF."

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

Phase 3 Trial of Pamrevlumab or Placebo in Combination With Systemic Corticosteroids in Participants With Ambulatory DMD (clinicaltrials.gov) - P3 | N=73 | Terminated | Sponsor: FibroGen | Trial completion date: May 2024 ➔ Dec 2023 | Active, not recruiting ➔ Terminated; Study did not meet its primary endpoint.

Combination therapy • Trial completion date • Trial termination • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

Pamrevlumab for Idiopathic Pulmonary Fibrosis: the ZEPHYRUS-1 Randomized Clinical Trial (ATS 2024) - "There is no abstract associated with this presentation."

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

Pamrevlumab for Idiopathic Pulmonary Fibrosis: Results of the Phase 3 Zephyrus-1 Study (ATS 2024) - P3 | "This study did not meet its primary efficacy endpoint: results observed with pamrevlumab trended toward improvement in time to disease progression, and measures of PROs trended toward better outcomes with pamrevlumab. No safety concerns were noted. These results are informative for planning future trials."

P3 data • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases • CTGF

Once-Promising Drug for Idiopathic Pulmonary Fibrosis Fails in Phase III Trial (MedPageToday) - "Among 356 patients with IPF, there was no statistically significant difference in absolute change in forced vital capacity (FVC) at 48 weeks versus baseline between those who took pamrevlumab and those in the placebo group (least-squares mean -260 mL vs -330 mL; P=0.29), reported Ganesh Raghu, MD...opens in a new tab or window annual meeting."

Media quote • Idiopathic Pulmonary Fibrosis

Pamrevlumab for Idiopathic Pulmonary Fibrosis: The ZEPHYRUS-1 Randomized Clinical Trial. (PubMed, JAMA) - P3 | "Phase 3 randomized clinical trial including 356 patients aged 40 to 85 years with idiopathic pulmonary fibrosis who were not receiving antifibrotic treatment with nintedanib or pirfenidone at enrollment. Among patients with idiopathic pulmonary fibrosis treated with pamrevlumab or placebo, there was no statistically significant between-group difference for the primary outcome of absolute change in FVC from baseline to week 48. ClinicalTrials.gov Identifier: NCT03955146."

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

FibroGen Reports First Quarter 2024 Financial Results (GlobeNewswire) - "Upcoming Milestones: Pamrevlumab: (i) Topline data from the PanCAN Precision Promise Phase 2/3 study of pamrevlumab in metastatic pancreatic cancer expected in mid-2024, reflecting PanCAN’s updated timing to complete database lock and subsequent analysis of the topline results by the independent Statistical Monitoring Committee; (ii) Topline data from the LAPIS Phase 3 study of pamrevlumab in locally advanced unresectable pancreatic cancer (LAPC) expected in 3Q 2024, due to the current trend in reported blinded overall survival events needed to complete the study."

P2/3 data • P3 data: top line • Pancreatic Cancer

Pamrevlumab: Expiry of patents related to composition-of-matter in US in 2025 with term extension until 2030 (FibroGen) - Annual Report 2023

Patent • Idiopathic Pulmonary Fibrosis • Respiratory Diseases

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 | Active, not recruiting | Sponsor: FibroGen | Trial completion date: Dec 2023 ➔ Apr 2024 | Trial primary completion date: Dec 2023 ➔ Apr 2024

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

FibroGen Virtual KOL Investor Event Series Part I: Review Pamrevlumab Clinical Program in Pancreatic Cancer and Its Two Near Term Readouts (LifeSci Events) - "Join FibroGen for Part I of a virtual KOL investor event series featuring Andrew Ko, MD...who will discuss the unmet medical need and current treatment landscape for pancreatic cancer, as well as the clinical development program for pamrevlumab, a potential first-in-class monoclonal antibody targeting connective tissue growth factor (CTGF) for pancreatic cancer treatment."

Live event

LELANTOS-2: primary and secondary endpoints were not met by pamrevlumab in ambulatory patients with Duchenne Muscular Dystrophy (DMD) (MDA 2024) - P3 | "All patients received systemic glucocorticoids (deflazacort or prednisone/prednisolone) during the study period. Pamrevlumab failed to meet its primary and secondary endpoints in the LELANTOS-2 pivotal Phase III study for ambulatory males with DMD. Pamrevlumab was generally well tolerated and no new safety concerns were identified for patients with DMD."

Clinical • Duchenne Muscular Dystrophy • Fibrosis • Genetic Disorders • Immunology • Muscular Dystrophy • CTGF

Pamrevlumab failed to meet primary and secondary endpoints for nonambulatory patients with Duchenne Muscular Dystrophy (DMD) in LELANTOS-1 (MDA 2024) - P3 | "All received systemic glucocorticoids (deflazacort or prednisone/prednisolone). Pamrevlumab failed to meet the primary and secondary endpoints, but was well tolerated in DMD patients."

Clinical • Duchenne Muscular Dystrophy • Fibrosis • Genetic Disorders • Immunology • Muscular Dystrophy • CTGF

Pamrevlumab failed to meet primary and secondary endpoints for nonambulatory patients with Duchenne Muscular Dystrophy (DMD) in LELANTOS-1 (MDA 2024) - No abstract available

Clinical • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy