PDF(Pubmed)
Abstract：
UNASSIGNED: FALCON 1 was a phase IIb study of pegbelfermin in patients with non-alcoholic steatohepatitis (NASH) and stage 3 fibrosis. This FALCON 1 post hoc analysis aimed to further assess the effect of pegbelfermin on NASH-related biomarkers, correlations between histological assessments and non-invasive biomarkers, and concordance between the week 24 histologically assessed primary endpoint response and biomarkers.
UNASSIGNED: Blood-based composite fibrosis scores, blood-based biomarkers, and imaging biomarkers were evaluated for patients with available data from FALCON 1 at baseline through week 24. SomaSignal tests assessed protein signatures of NASH steatosis, inflammation, ballooning, and fibrosis in blood. Linear mixed-effect models were fit for each biomarker. Correlations and concordance were assessed between blood-based biomarkers, imaging, and histological metrics.
UNASSIGNED: At week 24, pegbelfermin significantly improved blood-based composite fibrosis scores (ELF, FIB-4, APRI), fibrogenesis biomarkers (PRO-C3 and PC3X), adiponectin, CK-18, hepatic fat fraction measured by MRI-proton density fat fraction, and all four SomaSignal NASH component tests. Correlation analyses between histological and non-invasive measures identified four main categories: steatosis/metabolism, tissue injury, fibrosis, and biopsy-based metrics. Concordant and discordant effects of pegbelfermin on the primary endpoint vs. biomarker responses were observed; the most clear and concordant effects were on measures of liver steatosis and metabolism. A significant association between hepatic fat measured histologically and by imaging was observed in pegbelfermin arms.
UNASSIGNED: Pegbelfermin improved NASH-related biomarkers most consistently through improvement of liver steatosis, though biomarkers of tissue injury/inflammation and fibrosis were also improved. Concordance analysis shows that non-invasive assessments of NASH support and exceed the improvements detected by liver biopsy, suggesting that greater consideration should be given to the totality of available data when evaluating the efficacy of NASH therapeutics.
UNASSIGNED: Post hoc analysis of NCT03486899.
UNASSIGNED: FALCON 1 was a study of pegbelfermin vs. placebo in patients with non-alcoholic steatohepatitis (NASH) without cirrhosis; in this study, patients who responded to pegbelfermin treatment were identified through examination of liver fibrosis in tissue samples collected through biopsy. In the current analysis, non-invasive blood- and imaging-based measures of fibrosis, liver fat, and liver injury were used to determine pegbelfermin treatment response to see how they compared with the biopsy-based results. We found that many of the non-invasive tests, particularly those that measured liver fat, identified patients who responded to pegbelfermin treatment, consistent with the liver biopsy findings. These results suggest that there may be additional value in using data from non-invasive tests, along with liver biopsy, to evaluate how well patients with NASH respond to treatment.
UNASSIGNED: Blood-based composite fibrosis scores, blood-based biomarkers, and imaging biomarkers were evaluated for patients with available data from FALCON 1 at baseline through week 24. SomaSignal tests assessed protein signatures of NASH steatosis, inflammation, ballooning, and fibrosis in blood. Linear mixed-effect models were fit for each biomarker. Correlations and concordance were assessed between blood-based biomarkers, imaging, and histological metrics.
UNASSIGNED: At week 24, pegbelfermin significantly improved blood-based composite fibrosis scores (ELF, FIB-4, APRI), fibrogenesis biomarkers (PRO-C3 and PC3X), adiponectin, CK-18, hepatic fat fraction measured by MRI-proton density fat fraction, and all four SomaSignal NASH component tests. Correlation analyses between histological and non-invasive measures identified four main categories: steatosis/metabolism, tissue injury, fibrosis, and biopsy-based metrics. Concordant and discordant effects of pegbelfermin on the primary endpoint vs. biomarker responses were observed; the most clear and concordant effects were on measures of liver steatosis and metabolism. A significant association between hepatic fat measured histologically and by imaging was observed in pegbelfermin arms.
UNASSIGNED: Pegbelfermin improved NASH-related biomarkers most consistently through improvement of liver steatosis, though biomarkers of tissue injury/inflammation and fibrosis were also improved. Concordance analysis shows that non-invasive assessments of NASH support and exceed the improvements detected by liver biopsy, suggesting that greater consideration should be given to the totality of available data when evaluating the efficacy of NASH therapeutics.
UNASSIGNED: Post hoc analysis of NCT03486899.
UNASSIGNED: FALCON 1 was a study of pegbelfermin vs. placebo in patients with non-alcoholic steatohepatitis (NASH) without cirrhosis; in this study, patients who responded to pegbelfermin treatment were identified through examination of liver fibrosis in tissue samples collected through biopsy. In the current analysis, non-invasive blood- and imaging-based measures of fibrosis, liver fat, and liver injury were used to determine pegbelfermin treatment response to see how they compared with the biopsy-based results. We found that many of the non-invasive tests, particularly those that measured liver fat, identified patients who responded to pegbelfermin treatment, consistent with the liver biopsy findings. These results suggest that there may be additional value in using data from non-invasive tests, along with liver biopsy, to evaluate how well patients with NASH respond to treatment.
摘要：
未经证实：FALCON1是非酒精性脂肪性肝炎（NASH）和3期纤维化患者pegbelfermin的IIb期研究。FALCON1事后分析旨在进一步评估pegbelfermin对NASH相关生物标志物的影响，组织学评估与非侵入性生物标志物之间的相关性，以及第24周组织学评估的主要终点反应和生物标志物之间的一致性。
未经评估：基于血液的复合纤维化评分，基于血液的生物标志物，在基线至第24周,对具有来自FALCON1的可用数据的患者进行了成像生物标志物评估.SomaSignal测试评估了NASH脂肪变性的蛋白质特征，炎症,气球，和血液中的纤维化。线性混合效应模型适用于每种生物标志物。评估了血液生物标志物之间的相关性和一致性，成像,和组织学指标。
UNASSIGNED：在第24周，pegbelfermin显着改善了基于血液的复合纤维化评分（ELF，FIB-4，APRI），纤维发生生物标志物（PRO-C3和PC3X），脂联素,CK-18，通过MRI-质子密度脂肪分数测量的肝脂肪分数，和所有四个SomaSignalNASH组件测试。组织学和非侵入性措施之间的相关性分析确定了四个主要类别：脂肪变性/代谢，组织损伤,纤维化，和基于活检的指标。pegbelfermin对主要终点的一致和不一致作用与观察到生物标志物反应;最明显和一致的影响是对肝脏脂肪变性和代谢的测量。在pegbelfermin臂中观察到组织学测量和通过成像测量的肝脂肪之间的显着关联。
未经证实：Pegbelfermin通过改善肝脏脂肪变性最一致地改善NASH相关生物标志物，尽管组织损伤/炎症和纤维化的生物标志物也得到了改善。一致性分析显示，NASH的非侵入性评估支持并超过肝活检检测到的改善，提示在评估NASH治疗药物的疗效时,应更多地考虑现有的全部数据.
未经评估：对NCT03486899的事后分析。
未经批准：FALCON1是pegbelfermin与非酒精性脂肪性肝炎（NASH）无肝硬化患者的安慰剂；在这项研究中，对pegbelfermin治疗有反应的患者通过活检收集的组织样本中的肝纤维化检查进行鉴定。在目前的分析中,基于血液和成像的非侵入性纤维化措施，肝脏脂肪,和肝损伤被用来确定pegbelfermin治疗反应，看看他们如何与活检为基础的结果进行比较。我们发现许多非侵入性测试，尤其是那些测量肝脏脂肪的，确定了对pegbelfermin治疗有反应的患者，与肝活检结果一致。这些结果表明，使用来自非侵入性测试的数据可能有额外的价值，随着肝活检，评估NASH患者对治疗的反应。
未经评估：基于血液的复合纤维化评分，基于血液的生物标志物，在基线至第24周,对具有来自FALCON1的可用数据的患者进行了成像生物标志物评估.SomaSignal测试评估了NASH脂肪变性的蛋白质特征，炎症,气球，和血液中的纤维化。线性混合效应模型适用于每种生物标志物。评估了血液生物标志物之间的相关性和一致性，成像,和组织学指标。
UNASSIGNED：在第24周，pegbelfermin显着改善了基于血液的复合纤维化评分（ELF，FIB-4，APRI），纤维发生生物标志物（PRO-C3和PC3X），脂联素,CK-18，通过MRI-质子密度脂肪分数测量的肝脂肪分数，和所有四个SomaSignalNASH组件测试。组织学和非侵入性措施之间的相关性分析确定了四个主要类别：脂肪变性/代谢，组织损伤,纤维化，和基于活检的指标。pegbelfermin对主要终点的一致和不一致作用与观察到生物标志物反应;最明显和一致的影响是对肝脏脂肪变性和代谢的测量。在pegbelfermin臂中观察到组织学测量和通过成像测量的肝脂肪之间的显着关联。
未经证实：Pegbelfermin通过改善肝脏脂肪变性最一致地改善NASH相关生物标志物，尽管组织损伤/炎症和纤维化的生物标志物也得到了改善。一致性分析显示，NASH的非侵入性评估支持并超过肝活检检测到的改善，提示在评估NASH治疗药物的疗效时,应更多地考虑现有的全部数据.
未经评估：对NCT03486899的事后分析。
未经批准：FALCON1是pegbelfermin与非酒精性脂肪性肝炎（NASH）无肝硬化患者的安慰剂；在这项研究中，对pegbelfermin治疗有反应的患者通过活检收集的组织样本中的肝纤维化检查进行鉴定。在目前的分析中,基于血液和成像的非侵入性纤维化措施，肝脏脂肪,和肝损伤被用来确定pegbelfermin治疗反应，看看他们如何与活检为基础的结果进行比较。我们发现许多非侵入性测试，尤其是那些测量肝脏脂肪的，确定了对pegbelfermin治疗有反应的患者，与肝活检结果一致。这些结果表明，使用来自非侵入性测试的数据可能有额外的价值，随着肝活检，评估NASH患者对治疗的反应。
