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Pamrevlumab arm of the Precision PromiseSM study in metastatic pancreatic cancer, sponsored and conducted by the Pancreatic Cancer Action Network (PanCAN), did not meet the primary endpoint of overall survival as determined by the protocol pre-specified Bayesian statistical analysis LAPIS study in locally advanced, unresectable pancreatic cancer, sponsored by FibroGen, did not meet the primary endpoint of overall survival Pamrevlumab was generally safe and well tolerated across both studies, with no clinically meaningful difference in overall safety vs. control arms Company to implement immediate and significant cost reduction plan in the U.S. Terminate pamrevlumab research and development (R&D) investment and expeditiously wind down remaining obligations Reduce U.S. workforce by approximately 75% July 30, 2024 -- FibroGen, Inc. (NASDAQ: FGEN) today announced topline results from two late-stage trials evaluating the efficacy and safety of pamrevlumab in patients with pancreatic cancer and a corporate update. The pamrevlumab experimental arm in PanCAN’s Precision Promise Phase 2/3 adaptive platform trial compared treatment with pamrevlumab combined with gemcitabine + nab-paclitaxel to gemcitabine + nab-paclitaxel alone 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 combined with gemcitabine + nab-paclitaxel or FOLFIRINOX to placebo combined with gemcitabine + nab-paclitaxel or FOLFIRINOX for the treatment of locally advanced, unresectable pancreatic cancer (LAPC). The study did not meet the primary endpoint of overall survival. “We are deeply disappointed that the pamrevlumab arm in the Precision Promise trial and the LAPIS trial did not meet the primary endpoint of overall survival,” said Thane Wettig, Chief Executive Officer, FibroGen. “We were hopeful that pamrevlumab could bring meaningful innovation to pancreatic cancer patients in desperate need of new therapies. FibroGen would like to thank the patients, their families and the clinical trial investigators and teams for their dedication to participating in these studies. I would also like to express my deepest gratitude to our FibroGen colleagues who have dedicated so much of their time and energy for the prospect of bringing much needed therapies to some of the most challenging and deadly diseases affecting humanity.” Based upon the results of the late-stage pamrevlumab trials in pancreatic cancer, the Company plans to implement an immediate and significant cost reduction plan in the U.S. The pamrevlumab development program will be terminated and the Company plans to expeditiously wind down any remaining pamrevlumab obligations. As a result of the cost reduction plan, headcount in the U.S. will be reduced by approximately 75%. FibroGen’s collaboration agreement with AstraZeneca for roxadustat in China, where roxadustat is the market leader by brand value share in the chronic kidney disease (CKD) anemia category, as well as FibroGen’s collaboration agreement with Astellas for roxadustat in the E.U., Japan, and other territories, remain in place. Given both 1L and 2L pamrevlumab treatment groups graduated into Stage 2 of PanCAN’s Precision Promise study, the hazard ratio for the primary overall survival (OS) analysis assumed a common hazard ratio to estimate a single treatment effect for both 1L and 2L pamrevlumab patients combined compared to patients treated with gemcitabine + nab-paclitaxel. In addition, the pre-specified Bayesian model utilized a hierarchical model that included the borrowing of data from the mFOLFIRINOX control arm to the gemcitabine + nab-paclitaxel control arm for the primary efficacy analysis. The pre-specified primary efficacy analysis was performed in a modified intention-to-treat (mITT) population that included only subjects who initiated treatment. The mITT population in the pamrevlumab arm was comprised of a total of 102 patients in the 1L treatment group and 111 patients in the 2L treatment group and the gemcitabine + nab-paclitaxel control arm was comprised of a total of 34 patients in the 1L treatment group and 36 patients in the 2L treatment group. Primary OS Analysis as Determined by Pre-Specified Bayesian Statistical Analysis (mITT Population) Bayesian Model Common Hazard Ratio (HR)Posterior ProbabilityMedianMean (SD)95% CIPr(HR Primary Efficacy Analysis1.1701.184 (0.175)(0.882, 1.563)0.13977 LAPIS Efficacy Results The study did not meet the primary endpoint of overall survival (stratified log-rank p-value=0.55). Median overall survival of 17.3 months was observed in the pamrevlumab combined with gemcitabine + nab-paclitaxel or FOLFIRINOX arm compared to median overall survival of 17.9 months in the control arm of placebo combined with gemcitabine + nab-paclitaxel or FOLFIRINOX (HR: 1.08; 95% CI – 0.83 to 1.41). The preliminary safety analyses across both studies indicate that the safety profile of pamrevlumab combined with gemcitabine + nab-paclitaxel or FOLFIRINOX was generally well tolerated with an acceptable safety profile in pancreatic cancer patients. No clinically meaningful differences in treatment emergent adverse events were seen between the treatment arms. PanCAN’s Precision Promise adaptive platform trial (NCT04229004) is a U.S.-based, seamless Phase 2/3 study sponsored by PanCAN that enrolled patients in 24 sites nationwide. The multi-arm study consists of experimental treatment arms and two comparator arms: gemcitabine + nab-paclitaxel and mFOLFIRINOX. The pamrevlumab experimental arm enrolled 102 patients with mPDAC in first line (1L) and 111 patients with mPDAC in second line (2L). Both 1L and 2L patients received pamrevlumab in combination with gemcitabine and nab-paclitaxel. The final analysis was based upon the data collected up to 12 months after the last patient initiated treatment. The LAPIS study is a global Phase 3, randomized, double-blind trial to evaluate the efficacy and safety of neoadjuvant treatment with pamrevlumab or placebo in combination with either gemcitabine + nab-paclitaxel or FOLFIRINOX in the treatment of participants with locally advanced, unresectable pancreatic cancer (LAPC). The study enrolled 284 patients, who were randomized at a 1:1 ratio to receive either pamrevlumab or placebo, in combination with either gemcitabine + nab-paclitaxel or FOLFIRINOX. All patients were dosed up to six cycles of treatment and patients who completed study treatment were evaluated for surgical exploration for possible R0 or R1 resection. Participants who were ineligible for surgical exploration continued to receive treatment as per standard of care (SOC) for each institution. Pamrevlumab is a potential first-in-class anti-CTGF fully human monoclonal antibody being developed by FibroGen to inhibit the activity of connective tissue growth factor (CTGF). Pamrevlumab is in clinical development for the treatment of metastatic pancreatic cancer and locally advanced unresectable pancreatic cancer (LAPC). The U.S. Food and Drug Administration has granted Orphan Drug Designation for the treatment of patients with pancreatic ductal adenocarcinoma (PDAC), and Fast Track designation to pamrevlumab for the treatment of patients with LAPC. Pamrevlumab is an investigational drug and not approved for marketing by any regulatory authority. For information about our pamrevlumab studies please visit www.clinicaltrials.gov. FibroGen, Inc. is a biopharmaceutical company focused on accelerating the development of novel therapies at the frontiers of cancer biology. Roxadustat (爱瑞卓®, EVRENZOTM) is currently approved in China, Europe, Japan, and numerous other countries for the treatment of anemia in chronic kidney disease (CKD) patients on dialysis and not on dialysis. Roxadustat is in clinical development for chemotherapy-induced anemia (CIA) and a Supplemental New Drug Application (sNDA) has been accepted for review by the China Health Authority. FG-3246 (also known as FOR46), a first-in-class antibody-drug conjugate (ADC) targeting CD46 is in development for the treatment of metastatic castration-resistant prostate cancer. This program also includes the development of an associated CD46-targeted PET biomarker. In addition, FibroGen has expanded its research and development portfolio to include two immuno-oncology product candidates for the treatment of solid tumors. For more information, please visit www.fibrogen.com. The content above comes from the network. if any infringement, please contact us to modify.

FibroGen will cut about 75% of its workforce in the US after scrapping development of its lead pipeline hopeful pamrevlumab following the failure of two studies in pancreatic cancer. The news sent the company’s shares down over 44% in premarket trading on Wednesday.“We are deeply disappointed” in the results of the Precision Promise trial and the LAPIS study, remarked CEO Thane Wettig, which will result in “an immediate and significant cost reduction plan in the US.”The Phase II/III Precision Promise study, sponsored by PanCAN, included a pamrevlumab treatment arm that enrolled 102 patients with metastatic pancreatic ductal adenocarcinoma in first line and 111 participants in second line. Both groups received pamrevlumab, an anti-CTGF fully human monoclonal antibody, in combination with gemcitabine and nab-paclitaxel. Meanwhile, the Phase III LAPIS trial randomised 284 patients with locally advanced, unresectable pancreatic cancer to receive neoadjuvant treatment with pamrevlumab or placebo in combination with either gemcitabine and nab-paclitaxel or FOLFIRINOX. Top-line results showed that neither study met its primary endpoint of overall survival (OS). FibroGen noted that in the Precision Promise study, the mean hazard ratio for the primary efficacy analysis was 1.184, while in LAPIS, median OS was 17.3 months in the pamrevlumab arm compared to 17.9 months in the control arm.Focus on roxadustat, pipelineThe company indicated that following the termination of the pamrevlumab programme, it will focus on the renal anaemia treatment roxadustat and its pipeline of cancer drugs, led by the CD46-targeting antibody-drug conjugate FG-3246. Earlier this year, FibroGen regained certain rights to roxadustat from AstraZeneca amid stumbles for the oral HIF-PH inhibitor in the US. The drug is approved in China for renal anaemia patients on dialysis, while it is also sold in Europe under the name Evrenzo through a partnership with Astellas. However, in April, Astellas disclosed an impairment charge of around $100 million related to sluggish sales of Evrenzo having reviewed the "sales situation in each country."

FibroGen has not seen any late-stage success with pamrevlumab, with the therapy failing to meet primary endpoints in Phase III trials across multiple indications. Image Credit: Tatiana Stulbo / Shutterstock. FibroGen has implemented cost reduction measures in the US as two Phase III trials investigating the company’s lead oncology candidate pamrevlumab failed to meet their primary endpoints. The company plans to suspend the development of pamrevlumab and fire 75% of its US workforce. Following the announcement, FibroGen’s shares took a nosedive and dropped by approximately 40% in premarket trading today, compared to the market close on the previous day. The combination treatment of pamrevlumab and chemotherapy failed to meet the primary endpoint of overall survival in patients with locally advanced, unresectable pancreatic cancer in the Phase III LAPIS trial (NCT03941093). The same combination treatment also failed to achieve the primary endpoint of overall survival in patients with metastatic pancreatic ductal adenocarcinoma in a Phase II/III PanCAN’s Precision Promise trial (NCT04229004). FibroGen has not seen any late-stage success with pamrevlumab, with the therapy also failing to show efficacy in patients with Duchenne muscular dystrophy (DMD). Last year, the company announced disappointing results from two Phase III trials in DMD patients, after both failed to meet primary endpoints. Pamrevlumab is a monoclonal antibody that inhibits the activity of connective tissue growth factor (CTGF), which is involved in multiple tumour development and tissue fibrosis pathologies. See Also: FDA approves J&J’s multiple myeloma therapy Pharmaceutical Technology Excellence Awards 2024: SecureCHEK AI The company added that whilst it is winding down R&D activities for pamrevlumab, the commercial agreements for its anaemia therapy, roxadustat, will remain in place. Astellas holds the development and commercialisation rights to roxadustat in Japan, Europe, Turkey, Russia, the Commonwealth of Independent States, the Middle East, and South Africa. FibroGen has licensed roxadustat’s commercial rights in China and South Korea to AstraZeneca , where the drug is approved under the brand name Evrenzo . The company is expecting an approval decision for roxadustat in chemotherapy-induced anaemia (CIA) in China in H2 2024, which, if positive, will trigger a $10m milestone payment from AstraZeneca. Another oncology candidate in FIbroGen’s pipeline is a CD-46 targeting antibody-drug conjugate (ADC), FG-3246. The company licensed the therapy from Fortis Therapeutics in May 2023. In April, the company reported positive data from a Fortis-sponsored Phase I trial (NCT03575819) of the therapy involving metastatic castration-resistant prostate cancer patients. It demonstrated a median progression-free survival of 8.7 months and a prostate-specific antigen decrease of 50% or more in 36% of participants.