FibroGen Announces Topline Results from Two Late-Stage Pamrevlumab Pancreatic Cancer Studies and Provides Corporate Update
FibroGen (NASDAQ: FGEN) announced disappointing results from two late-stage trials evaluating pamrevlumab in pancreatic cancer patients. The pamrevlumab arm in PanCAN's Precision Promise study for metastatic pancreatic cancer and the Phase 3 LAPIS trial for locally advanced, unresectable pancreatic cancer both failed to meet the primary endpoint of overall survival. In response, FibroGen plans to terminate the pamrevlumab development program and implement a significant cost reduction plan, including a 75% reduction in U.S. workforce. The company will focus on its collaboration with AstraZeneca for roxadustat in China and with Astellas in other territories. Despite the setback, pamrevlumab was generally safe and well-tolerated across both studies.
FibroGen (NASDAQ: FGEN) ha annunciato risultati deludenti da due studi di fase avanzata che valutano pamrevlumab in pazienti con cancro pancreatico. Il braccio di pamrevlumab nello studio Precision Promise di PanCAN per il cancro pancreatico metastatico e il trial di fase 3 LAPIS per il cancro pancreatico localmente avanzato e non resecabile non hanno raggiunto l'obiettivo primario di sopravvivenza globale. In risposta, FibroGen intende terminare il programma di sviluppo di pamrevlumab e attuare un piano significativo di riduzione dei costi, che include una riduzione del 75% della forza lavoro negli Stati Uniti. L'azienda si concentrerà sulla collaborazione con AstraZeneca per roxadustat in Cina e con Astellas in altre aree. Nonostante il contrattempo, pamrevlumab si è rivelato generalmente sicuro e ben tollerato in entrambi gli studi.
FibroGen (NASDAQ: FGEN) anunció resultados decepcionantes de dos ensayos de fase avanzada que evaluaron pamrevlumab en pacientes con cáncer de páncreas. El grupo de pamrevlumab en el estudio Precision Promise de PanCAN para cáncer de páncreas metastásico y el ensayo de fase 3 LAPIS para cáncer de páncreas localmente avanzado y no resecable no lograron cumplir con el objetivo primario de supervivencia general. En respuesta, FibroGen planea terminar el programa de desarrollo de pamrevlumab e implementar un importante plan de reducción de costos, que incluye una reducción del 75% de la fuerza laboral en EE. UU.. La empresa se centrará en su colaboración con AstraZeneca para roxadustat en China y con Astellas en otros territorios. A pesar del contratiempo, pamrevlumab fue generalmente seguro y bien tolerado en ambos estudios.
FibroGen (NASDAQ: FGEN)은 췌장암 환자에서 pamrevlumab을 평가한 두 개의 후기 단계 시험에서 실망스러운 결과를 발표했습니다. 전이성 췌장암에 대한 PanCAN의 Precision Promise 연구와 국소 진행성, 절제 불가능한 췌장암에 대한 3상 LAPIS 시험 모두 전체 생존율의 주요 목표를 달성하지 못했습니다. 이에 FibroGen은 pamrevlumab 개발 프로그램을 종료할 계획이며, 미국 인력의 75%를 감축하는 대규모 비용 절감 계획을 시행할 예정입니다. 회사는 중국에서의 roxadustat에 대한 AstraZeneca와의 협력 및 기타 지역에서의 Astellas와의 협력에 집중할 것입니다. setback에도 불구하고, pamrevlumab은 두 연구에서 일반적으로 안전하고 잘 견뎌냈습니다.
FibroGen (NASDAQ: FGEN) a annoncé des résultats décevants de deux essais avancés évaluant pamrevlumab chez des patients atteints de cancer du pancréas. Le bras pamrevlumab de l'étude Precision Promise de PanCAN pour le cancer du pancréas métastatique et l'essai de phase 3 LAPIS pour le cancer du pancréas localement avancé et non résécable n'ont pas atteint l'objectif principal de survie globale. En réponse, FibroGen prévoit de terminer le programme de développement de pamrevlumab et de mettre en œuvre un plan significatif de réduction des coûts, y compris une réduction de 75 % de son personnel aux États-Unis. L'entreprise se concentrera sur sa collaboration avec AstraZeneca pour le roxadustat en Chine et avec Astellas dans d'autres territoires. Malgré ce revers, pamrevlumab s'est montré généralement sûr et bien toléré dans les deux études.
FibroGen (NASDAQ: FGEN) gab enttäuschende Ergebnisse aus zwei späten klinischen Studien bekannt, die pamrevlumab bei Patienten mit Bauchspeicheldrüsenkrebs untersuchten. Die pamrevlumab-Gruppe in der Precision Promise-Studie von PanCAN für metastasierten Bauchspeicheldrüsenkrebs und die Phase-3-LAPIS-Studie für lokal fortgeschrittenen, nicht operablen Bauchspeicheldrüsenkrebs erreichten beide nicht das primäre Ziel der Gesamtüberleben. Als Reaktion darauf plant FibroGen, das Entwicklungsprogramm für pamrevlumab zu beenden und einen bedeutenden Kostenreduktionsplan umzusetzen, einschließlich einer Reduktion der US-Belegschaft um 75%. Das Unternehmen wird sich auf die Zusammenarbeit mit AstraZeneca für Roxadustat in China und mit Astellas in anderen Regionen konzentrieren. Trotz des Rückschlags war pamrevlumab in beiden Studien im Allgemeinen sicher und gut verträglich.
- Pamrevlumab was generally safe and well-tolerated across both studies
- FibroGen's collaboration agreements with AstraZeneca and Astellas for roxadustat remain in place
- Roxadustat is the market leader by brand value share in the chronic kidney disease anemia category in China
- Pamrevlumab failed to meet the primary endpoint of overall survival in both pancreatic cancer trials
- FibroGen to terminate pamrevlumab research and development program
- Company to reduce U.S. workforce by approximately 75%
- Immediate and significant cost reduction plan to be implemented in the U.S.
Insights
The results of FibroGen's late-stage trials for pamrevlumab in pancreatic cancer are undoubtedly a significant setback for the company and the field of pancreatic cancer research. As an oncology research analyst, I find several key points worth highlighting:
- The failure to meet the primary endpoint of overall survival in both the Precision Promise and LAPIS studies is particularly disappointing, given the urgent need for new effective therapies in pancreatic cancer, which remains one of the deadliest forms of cancer.
- The Precision Promise study's innovative adaptive platform design and Bayesian statistical analysis approach were noteworthy. However, the posterior probability of
13.977% for the hazard ratio being less than 1 indicates a low likelihood of pamrevlumab providing a survival benefit. - In the LAPIS study, the median overall survival of 17.3 months for the pamrevlumab arm compared to 17.9 months for the control arm (HR: 1.08; 95% CI – 0.83 to 1.41) suggests no meaningful improvement and possibly a slight detriment, though not statistically significant.
- The safety profile of pamrevlumab appears acceptable, which is a silver lining, but unfortunately not sufficient given the lack of efficacy.
These results underscore the challenges in developing effective treatments for pancreatic cancer and highlight the need for continued research into novel approaches and targets. The failure of pamrevlumab, which targets connective tissue growth factor (CTGF), suggests that this pathway may not be as critical in pancreatic cancer progression as previously hoped.
The negative trial results for pamrevlumab have significant financial implications for FibroGen:
- The immediate termination of the pamrevlumab development program represents a major shift in FibroGen's R&D strategy and pipeline.
- The planned
75% reduction in U.S. workforce indicates a drastic restructuring, which will likely result in substantial one-time costs but should lead to significant ongoing cost savings. - With pamrevlumab's failure, FibroGen's near-term growth prospects now heavily rely on roxadustat's performance in China, where it's the market leader in CKD anemia treatment.
- The company's collaborations with AstraZeneca for roxadustat in China and with Astellas in other territories become even more critical for FibroGen's future.
Investors should expect significant volatility in FibroGen's stock price as the market digests this news. The company's ability to quickly implement its cost reduction plan and potentially redirect resources to other promising areas will be crucial. Additionally, any updates on roxadustat's performance in China and other markets will likely become key drivers for the stock in the near term.
Looking ahead, FibroGen's pipeline beyond pamrevlumab and its cash position will be important factors to monitor. The company may need to consider strategic alternatives, including potential M&A activity or licensing deals, to bolster its pipeline and long-term prospects.
- 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%
SAN FRANCISCO, July 30, 2024 (GLOBE NEWSWIRE) -- 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
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.
PanCAN’s Precision Promise Pamrevlumab Arm Efficacy Results
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 Probability | |||
| Median | Mean (SD) | Pr(HR < 1) | ||
| Primary Efficacy Analysis | 1.170 | 1.184 (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;
Pamrevlumab Safety Results (Precision Promise and LAPIS)
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.
About PanCAN’s Precision Promise
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.
About LAPIS
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.
About Pamrevlumab
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.
About FibroGen
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.
Forward-Looking Statements
This release contains forward-looking statements regarding FibroGen’s strategy, future plans and prospects, including statements regarding its clinical programs and those of the Pancreatic Cancer Action Network and the Company’s future focus. These forward-looking statements include, but are not limited to, statements regarding the efficacy, safety, and potential success of FibroGen product candidates, and statements about FibroGen’s plans and objectives and typically are identified by use of terms such as “may,” “will”, “should,” “on track,” “could,” “expect,” “plan,” “anticipate,” “believe,” “estimate,” “predict,” “potential,” “continue” and similar words, although some forward-looking statements are expressed differently. FibroGen’s actual results may differ materially from those indicated in these forward-looking statements due to risks and uncertainties related to the continued progress and timing of its various programs, including the enrollment and results from ongoing and potential future clinical trials, and other matters that are described in FibroGen’s Annual Report on Form 10-K for the fiscal year ended December 31, 2023, and its Quarterly Report on Form 10-Q for the quarter ended March 31, 2024, as filed with the Securities and Exchange Commission (SEC), including the risk factors set forth therein. Investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date of this release, and FibroGen undertakes no obligation to update any forward-looking statement in this press release, except as required by law.
For Investor Inquiries:
David DeLucia, CFA
Vice President of Corporate FP&A / Investor Relations
ir@fibrogen.com
For Media Inquiries:
Simon Miller
Vice President, Marketing and Corporate Communications
media@fibrogen.com
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