Nintedanib(BIBF1120)相关信息

Efficacy and Safety of Nintedanib in Idiopathic Pulmonary Fibrosis

Abstract
BACKGROUND: Nintedanib (formerly known as BIBF 1120) is an intracellular inhibitor that targets multiple tyrosine kinases. A phase 2 trial suggested that treatment with 150 mg of nintedanib twice daily reduced lung-function decline and acute exacerbations in patients with idiopathic pulmonary fibrosis.

METHODS: We conducted two replicate 52-week, randomized, double-blind, phase 3 trials (INPULSIS-1 and INPULSIS-2) to evaluate the efficacy and safety of 150 mg of nintedanib twice daily as compared with placebo in patients with idiopathic pulmonary fibrosis. The primary end point was the annual rate of decline in forced vital capacity (FVC). Key secondary end points were the time to the first acute exacerbation and the change from baseline in the total score on the St. George's Respiratory Questionnaire, both assessed over a 52-week period.

RESULTS: A total of 1066 patients were randomly assigned in a 3:2 ratio to receive nintedanib or placebo. The adjusted annual rate of change in FVC was -114.7 ml with nintedanib versus -239.9 ml with placebo (difference, 125.3 ml; 95% confidence interval [CI], 77.7 to 172.8; P<0.001) in INPULSIS-1 and -113.6 ml with nintedanib versus -207.3 ml with placebo (difference, 93.7 ml; 95% CI, 44.8 to 142.7; P<0.001) in INPULSIS-2. In INPULSIS-1, there was no significant difference between the nintedanib and placebo groups in the time to the first acute exacerbation (hazard ratio with nintedanib, 1.15; 95% CI, 0.54 to 2.42; P=0.67); in INPULSIS-2, there was a significant benefit with nintedanib versus placebo (hazard ratio, 0.38; 95% CI, 0.19 to 0.77; P=0.005). The most frequent adverse event in the nintedanib groups was diarrhea, with rates of 61.5% and 18.6% in the nintedanib and placebo groups, respectively, in INPULSIS-1 and 63.2% and 18.3% in the two groups, respectively, in INPULSIS-2.

CONCLUSIONS: In patients with idiopathic pulmonary fibrosis, nintedanib reduced the decline in FVC, which is consistent with a slowing of disease progression; nintedanib was frequently associated with diarrhea, which led to discontinuation of the study medication in less than 5% of patients. (Funded by Boehringer Ingelheim; INPULSIS-1 and INPULSIS-2 ClinicalTrials.gov numbers, NCT01335464 and NCT01335477.).

http://www.nejm.org/doi/full/10.1056/NEJMoa1402584

Phase I Safety, Pharmacokinetic, and Biomarker Study of BIBF 1120, an Oral Triple Tyrosine Kinase Inhibitor in Patients with Advanced Solid Tumors

Abstract
BIBF 1120 is an oral multitargeted tyrosine kinase inhibitor that blocks the activity of vascular endothelial growth factor (VEGF) and other growth factor receptors. We have done a phase I study to evaluate the safety, pharmacokinetics, and pharmacodynamic biomarkers of BIBF 1120. Patients with advanced refractory solid tumors were treated with BIBF 1120 at oral doses of 150 to 250 mg twice daily. Drug safety and pharmacokinetics were evaluated, as were baseline and post-treatment levels of circulating CD117-positive bone marrow–derived progenitor cells and plasma soluble VEGF receptor 2 as potential biomarkers for BIBF 1120. Twenty-one patients were treated at BIBF 1120 doses of 150 (n = 3), 200 (n = 12), or 250 mg twice daily (n = 6). Dose-limiting toxicities of reversible grade 3 or 4 elevations of liver enzymes occurred in 3 of 12 patients at 200 mg twice daily and 3 of 6 patients at 250 mg twice daily. Stable disease was achieved in 16 (76.2%) patients,and median progression-free survival was 113 days (95% confidence interval, 77-119 d). Pharmacokinetic analysis indicated that the maximum plasma concentration and area under the curve for BIBF 1120 increased with the dose within the dose range tested. Levels of CD117-positive bone marrow–derived progenitors and soluble VEGF receptor 2 decreased significantly during treatment over all BIBF 1120 dose cohorts. In conclusion, the maximum tolerated dose of BIBF 1120 in the current study was determined to be 200 mg twice daily, and our biomarker analysis indicated that this angiokinase inhibitor is biologically active. Mol Cancer Ther; 9(10); 2825–33. &copy;2010 AACR.

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Abstract PD5-8: Phase I clinical trial of neoadjuvant BIBF1120 plus weekly paclitaxel (P) in early HER-2 negative breast cancer. CNIO-BR-01-2010/GEICAM 2010-10 study

Abstract

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Background: BIBF1120 has shown promising preclinical efficacy in breast cancer, and weekly paclitaxel (P) is a standard of care in BC. We designed a phase I/II trial of BIBF 1120 plus weekly P in early breast cancer, and report here the phase I part of the trial. The recommended dose has been determined and, additionally, efficacy has been assessed.

Methods: Eligible patients had pathologically confirmed HER2 negative stage II or IIIA untreated breast cancer. BIBF1120 and P were administered at the following dose levels (DL): DL1: BIBF1120 150 mg bid p.o. days 1-21 plus P 80 mg/ m2 iv on days 1, 8 and 15 q21 days; DL2: BIBF1120 200 mg bid p.o. days 1-21 plus P same dose as level 1, q21 days. On the P-infusion day, the morning BIBF1120 dose was skipped to avoid potential PK interactions. A 3+3 escalation scheme with common dose-limiting toxicity (DLT) definitions was adopted. Four three-week cycles of BIBF1120 plus P followed by 4 AC cycles were administered. Surgery was planned 4-5 weeks after the last AC dose. We report the phase I part results of the phase I/II trial.

Results: 9 patients have been evaluated for toxicity (6 patients in DL1 and 3 in DL2). Median age was 47.6 years (38.1-66.7) and 8 patients (89%) were premenopausal; median tumour size was 3.0 cm (2.7-6.5), 6 patients (66.7%) had stage II disease and 3 patients (33.3%) stage III. Seven cases (78%) were hormone-receptor (HR) positive and 2 (22%) negative. Two patients had DLT at DL2: ALT grade 3 (one patient); and ALT grade 4, AST grade 3 and GGT grade 3 (one patient). One case was reduced to DL1 and one withdrew consent after 7 days of treatment. Main related toxicities during treatment: DL1 GGT grade 2 (16.7%), hypertension grade 2 (50%), DL2 ALT grade 3 (33.3%), AST grade 3 (33.3%), bilirubin grade 2 (33.3%), GGT grade 2/3 (100%). Toxicities observed at DL2 were reversible by withholding BIBF1120 administration. Eight patients were evaluable for efficacy after surgery and have been assessed for pathological response: 2/2 (100%) HR(-) and 2/6 (33%) HR(+) patients, for a total of 4/8 (50%) patients, pCR defined as Miller&Payne score scale of 5. Three of these received DL1 and 1 DL2. A total of 6 patients (75%) underwent conservative surgery.

Conclusions: Concomitant administration in early stage HER-2 negative breast cancer of BIBF1120 plus P at DL1 was manageable and had mild toxicity, showing remarkable efficacy specially in triple-negative breast cancer. BIBF1120 150 mg bid plus weekly P 80mg/m2 is the recommended dose for the ongoing phase II part of study CNIO-BR-01-2012/GEICAM 2010-10 with an enrolment target of 130 patients, of which 81 have been already recruited.

Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr PD5-8.

http://cancerres.aacrjournals.or ... plement/PD5-8.short

Nintedanib (BIBF 1120) plus docetaxel in NSCLC patients progressing after first-line chemotherapy: LUME Lung 1, a randomized, double-blind phase III trial.

Abstract:

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Background: Nintedanib (N) inhibits VEGFRs, PDGFRs, and FGFRs. LUME Lung 1 is a placebo (P) controlled phase III trial of N + docetaxel (D) in patients (pts) with locally advanced/metastatic NSCLC progressing after first-line therapy.

Methods: Stage IIIB/IV or recurrent NSCLC pts (stratified by histology, ECOG PS, prior bevacizumab, and brain metastases) were randomized to N 200 mg bid + D 75 mg/m2 q21d (n=655) or P + D (n=659). 1° endpoint was centrally reviewed PFS after 713 events (2 sided stratified log-rank, α=5%, β=10%). Key 2° endpoint of OS was analyzed hierarchically after 1,121 events (2 sided, adjusted α=4.98%, β=20%), first in adenocarcinoma (adeno) pts <9 mo since start of first-line therapy (T<9mo; identified as a prognostic/predictive biomarker [ASCO ‘13]), followed by all adeno pts and then all pts. Predefined sensitivity analyses added sum of longest diameters of target lesions (SLD) to stratification factors in the Cox model.

Results: Pt characteristics were balanced between the arms. N + D significantly prolonged PFS vs P + D (HR 0.79; CI: 0.68, 0.92; p=0.0019; median 3.4 vs 2.7 mo) regardless of histology (squamous HR 0.77, p=0.02; adeno HR 0.77, p=0.02). OS was significantly prolonged in all adeno pts (HR 0.83; p=0.0359; median 12.6 vs 10.3 mo) with the greatest improvement seen in T<9mo adeno pts (HR 0.75; p=0.0073; median 10.9 vs 7.9 mo). A trend for improved OS was seen in all pts (HR 0.94; p=0.272; median 10.1 vs 9.1). When adjusted for SLD, a significant OS benefit was seen in all pts (HR 0.88; CI: 0.78, 0.99; p=0.0365). Disease control rates were significantly improved with N + D in all adeno pts (odds ratio [OR] 1.93; p<0.0001), T<9mo adeno pts (OR 2.90; p<0.0001) and all pts (OR 1.68; p<0.0001). The most common AEs were diarrhea (any: 42.3 vs 21.8%; Gr ≥3: 6.6 vs 2.6%) and ALT elevations (any: 28.5 vs 8.4%; Gr ≥3: 7.8 vs 0.9%). Incidence of CTCAE Gr ≥3 AEs was 71.3 vs 64.3%. Withdrawals due to AEs (22.7 vs 21.7%) were similar in both arms, as were Gr ≥3 hypertension, bleeding or thrombosis.

Conclusions: N + D significantly improved PFS independent of histology, and prolonged OS for adeno pts. AEs were generally manageable with dose reductions and symptomatic treatment. Clinical trial information: NCT00805194.

http://meetinglibrary.asco.org/content/111857-132

Phase II trial of triple tyrosine kinase receptor inhibitor nintedanib in recurrent high-grade gliomas: Final results.

Abstract:

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Background: Bevacizumab is FDA-approved for patients with recurrent GBM. However, the median duration of response is only 4 months. Potential mechanisms of resistance include upregulated FGF signaling and increased PDGF-mediated pericyte coverage. Nintedanibis an oral, small-molecule tyrosine kinase inhibitor of PDGFR α/β, FGFR 1-3, and VEGFR 1-3 that may overcome resistance to prior anti-VEGF therapy.

Methods: This was an open-label, phase II trial in adults with first or second recurrence of GBM, stratified by prior bevacizumab. The primary endpoint was PFS6 in the bevacizumab-naive arm (arm A) and PFS3 in the post-bevacizumab arm (arm B). A Simon two-stage design was employed. Up to 10 anaplastic glioma (AG) patients were accrued to each arm in exploratory cohorts.

Results: Twenty-two patients enrolled in Arm A and 14 in Arm B. Accrual to both arms was stopped after the first stage due to futility. Arm A included 12 GBMs (55%), 13 patients with one prior regimen (59%), and median age 54 years (range 28-75). Arm B included 10 GBMs (71%), one patient with one prior regimen (7%), and median age 52 years (range 32-70). Median KPS overall was 90 (range 60-100). There were no responses. In Arm A (GBM only), PFS6 was 0%, median PFS 28 days (95% CI: 27-83), and median OS 6.9 months (3.7-8.1). In Arm B (GBM only), PFS3 was 0%, median PFS 28 days (22-28), and median OS 2.6 months (1.0-6.9). In Arm A (AG only), PFS6 was 0% and median PFS 28 days (27-68). In Arm B (AG only), PFS3 was 0% and median PFS 28 days (7-56). Rare grade >3 toxicities included transaminase elevation, hypophosphatemia, hypertension, intracranial hemorrhage, and abdominal pain. Two participants died during therapy, one from thromboembolism and one from colon perforation.

Conclusions: Nintedanib is not active against recurrent high-grade glioma, regardless of prior bevacizumab therapy. Clinical trial information: NCT01380782.

http://meetinglibrary.asco.org/content/129210-144

Independent review of AGO-OVAR 12, a GCIG/ENGOT-Intergroup phase III trial of nintedanib (N) in first-line therapy for ovarian cancer (OC).

Abstract:

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Background: N is an oral inhibitor of VEGFR, PDGFR, and FGFR. As reported earlier, in the AGO-OVAR12 trial, N compared to placebo (Pl), added to standard chemotherapy, significantly prolonged investigator (inv)-determined PFS (1° endpoint [EP]) in first-line OC. Here we report independent review committee (IRC)-determined PFS. Methods: IRC-PFS was predefined as sensitivity analysis to the 1° EP (database lock triggered by inv-PFS events). IRC-PFS was analyzed in the intent-to-treat population (n=1366), based on RECIST 1.1 and restrictive predefined clinical (clin) criteria. Debulking surgery details were provided to the IRC radiologist to support assessment of baseline (BL) tumor burden, and additional clin data to the IRC oncologist for a final integrative review.

Results: Adherence to prescheduled imaging within 4 weeks of the prescribed date was high (>75%); independent review was completed for 94% of patients (pts). The IRC identified 4.3% of pts without tumor lesions at BL compared to 31.5% in on-site imaging; and 50.7% were stratified as free of residual tumor (integrating also surgery information) at randomization. Event concordance between IRC- and inv-PFS was very high (85.8%). Low discordance overall was primarily due to 19.5% (N) and 16.5% (Pl) of inv-determined PFS events (n=752 events) not detected by IRC, IRC detected an event in 9.2% (N) and 8.5% (Pl) of patients without inv-determined event (IRC total n=668 events). Concordance for event date was high, 75% of dates differed by <4 weeks. IRC-PFS was similar to inv-PFS (IRC: HR 0.86 [0.74-1.01], mPFS N=19.5 mo vs Pl=16.8 mo; inv: HR 0.84 [0.72-0.98], mPFS N=17.2 mo vs Pl=16.6 mo). Outcome of post hoc defined subgroup analysis (risk groups by stage and tumor burden) were also similar (‘low-risk’, IRC: HR 0.77 [0.62-0.96], mPFS N=27.8 mo vs Pl=21.9 mo; inv: HR 0.74 [0.61-0.91], mPFS N=27.1 mo vs Pl=20.8 mo).

Conclusions: IRC-PFS (sensitivity analysis of 1° was highly concordant with inv-PFS regarding PFS events, event dates, and overall outcome. Consistency of BL tumor assessment by the IRC, site-radiologists and clinical inv was low, possibly affecting individual PFS assessment but not overall HR. Clinical trial information: NCT01015118.

http://meetinglibrary.asco.org/content/130341-144

芙蓉姐翻译


非小细胞肺癌（NSCLC）患者在接受nintedanib（N）和多西他赛（D）治疗中的抗血管生成特定的不良事件（AEs）（2014 美国临床肿瘤学会）
摘要
背景:抗血管新生治疗,包括单克隆抗体和TKIs,显示肿瘤的活动; 然而,他们有限的使用部分是由于特性的副作用(如出血、血栓形成、穿孔、严重皮肤反应、高血压)。N （nintedanib）口服,每日两次,是三重angiokinase抑制剂。我们扩展我们的调查LUME-Lung 1研究(临床试验&#8226;&#8226;gov  NCT00805194)和评估添加N标准二线D是否增加抗血管生成药物关联的特性副作用发生的频率和这些副作用是否限制了使用N . 方法UME-Lung 1,一项随机、安慰剂对照III期试验研究N + D在晚期非小细胞肺癌患者的一线化疗失败后,显著地提高PFS不论组织学，显示明显提高患者的腺癌生存。抗血管生成关联的 AEs的发病率和强度根据常见术语标准AEs(CTCAE版本3.0)评估所有病人至少接受一剂N,D,或安慰剂(Pl)。结果VEGF抑制剂AEs更常见(≥2%的差异)在N和Pl组出血(所有等级:14.1% vs 11.6%;等级≥3:2.3% vs 1.8%)和高血压(所有等级:3.5% vs 0.9%;等级≥3:0.6% vs 0.2%)。当我们比较组织学抗血管生成关联 AEs的差异时,我们发现了名义上的差异。更多流血事件被报道为N -治疗鳞状细胞癌(SCC)患者(所有等级:17.1% vs 10.9%;等级≥3:2.9% vs 1.3%)超过那些腺癌(所有等级:10.9% vs 11.1%;等级≥3:1.5% vs 1.3%)。致命的出血事件、严重皮肤反应、血栓形成和穿孔发生频率低,双组之间的平衡,无论组织学。结论:我们证明添加N为非小细胞肺癌二线标准D治疗不会增加抗血管新生治疗相关AEs的频率,除了1 - 2级鳞状细胞癌患者的出血事件。这些AEs平衡无论组织学LUME-Lung 1。临床试验信息:NCT00805194。

Lume-lung 2:多中心、随机、双盲、nintedanib III期研究,加上培美曲塞与安慰剂组加上培美曲塞非鳞非小细胞肺癌(NSCLC)后一线化疗的失败后晚期患者。(2013 ASCO)
摘要
  背景:Nintedanib(N)是一种口服VEGFR,FGFR和PDGFR抑制剂。这个全球第三阶段的安全性和有效性研究调查了N +培美曲塞(PEM)与安慰剂(P)+ PEM的病人(pts)和晚期,非鳞 NSCLC之前曾接受化疗的患者。方法:随机分1:1 N 200毫克  口服 一天两次报+ PEM 500 mg / m2 静脉点滴 每21天(N = 353、组A)或P + PEM(N = 360、组B)。延续直到PD或N,P,PEM不可接受的毒性与，或二者联合是允许的。1°端点被集中审查的PFS。无效假设是在ITT人群测试发生后394事例（双面α=5％）。2°端点包括OS、研究者评价的 PFS,反应率(RR),安全,和生命质量。结果:基线pt特点是组 A和B之间是均衡的  (平均年龄59岁,女性45 - 42%,ECOG PS 1   62 - 61% , 腺癌95 - 93%, 贝伐单抗前8%)。根据研究者评价的PFS计划DMC无用分析，计划一千三，随机招募七百十三（确定没有安全问题）后停止。正在进行的患者进行揭盲和每个协议的后续随访。 1°端点（集中讨论PFS）随后的ITT分析的青睐A组向对B组（中位数4.4比3.6月，HR0.83[95％CI：0.7-0.99]，P = 0.04）。N治疗过的患者疾病控制也显著的改善（61与53％，比值比为1.37，P = 0.039）。在OS（HR1.03）或RR（9％）无显着差异。探索性分析确定的时间从第一线疗法开始作为与N+ PEM（ASCO2013）改进的结果的预测指标的开始。N + PEM患者没有增加严重不良反应或不良事件。添加N+PEM导致≥G3 谷丙转氨酶ALT升高（23比7％），谷草转氨酶AST升高（12比2％），腹泻（3比1％）的发生率较高，但在≥G3高血压没有什么区别，出血，血栓形成，黏膜炎，或神经病变。结论：1即使研究提前终止。治疗N+ PEM与P+PEM相比较显著改善的先前接受化疗治疗晚期非鳞状非小细胞肺癌PFS，并有一个可管理的安全性。临床试验信息：NCT00806819。

Nintedanib(BIBF 1120)加上多烯紫杉醇在非小细胞肺癌患者一线化疗后进展: LUME Lung 1,随机,双盲III期试验。(2013 ASCO)
摘要
    背景:Nintedanib(N)抑制VEGFRs PDGFRs,FGFRs。LUME Lung 1是局部晚期或转移性非小细胞肺癌一线治疗后进展N +多烯紫杉醇(D)的III期试验 (pts)控制的安慰剂。方法 IIIB:/ IV或复发性非小细胞肺癌(由组织学分层,ECOG PS,贝伐单抗之前,和脑转移)随机给予N 200毫克  每天两次+ D 75 mg / m2每21天(N = 655)或P + D(N = 659)。1°端点 713事例后集中讨论了PFS (log-rank双面分层l,α= 5%,β= 10%)。关键2°端点1121事例后分层次的分析了OS(2站,调整α= 4.98%,β= 20%),首先在腺癌(adeno)分< 9 mo一线疗法开始以来,(T < 9mo;认定为预后/预测生物标志物(ASCO 13]),然后所有腺的病人，然后所有的病人。预定义的敏感度分析靶病灶（SLD）的最长直径总和添加到分层因素的Cox模型。结果t特点是组之间的平衡。N + DS与P + D相比较显著延长PFS(HR 0.79;CI:0.79,0.68,P = 0.0019;平均3.4 vs 2.7 mo)无论组织学(鳞状HR0.77,P = 0.02;腺  HR  0.77,P = 0.02)。OS显著延长所有腺癌 pts(HR 0.83;p = 0.0359;中位数12.6 vs 10.3 mo)中值最大的改进在T < 9mo  腺癌 pts(HR 0.75;p = 0.0073;中位数10.9 vs 7.9 mo)。有一种趋势，在所有患者以提高OS可见（HR =0.94，P=0.272，中位数10.1比9.1）。当调整SLD，一个显著OS获益见于所有患者（HR0.88，CI：0.78，0.99，P=0.0365）。N + D治疗所有的腺癌患者疾病控制率显著提高了(优势比[或]1.93;p < 0.0001),T < 9mo 腺癌患者(或2.90,p < 0.0001)和所有患者(或1.68,p < 0.0001)。最常见的副作用腹泻(任何:42.3 vs 21.8%;Gr≥3:6.6和2.6%)和谷丙转氨酶ALT升高(任何:28.5 vs 8.4%;Gr≥3:7.8和0.9%)。CTCAE的发生率 Gr≥3 AEs为71.3和64.3%。退出由于双组(21.7% vs 22.7)相似副作用,是Gr≥3高血压、出血或血栓形成。结论:N + D显著改善PFS，无论组织学,延长腺癌患者的OS。副作用可通过剂量减少和对症治疗控制。临床试验信息:NCT00805194。

Y爷，你好厉害~~~

http://news.medlive.cn/cancer/info-progress/show-64285_53.html

关于Nintedanib药物的研究是LUME-Lung1研究，一项Nintedanib+多西他赛 vs 安慰剂+多西他赛对IIIB/IV期和/或复发NSCLC患者的疗效比较试验，主要终点是PFS（独立中心评估），次要终点是OS（预设全组和腺癌亚组）。从这项试验我们可以得出，LUME-Lung1研究达到主要终点：Nintedanib+多西他赛显著改善全组PFS（HR=0.79；P=0.0019）；腺癌亚组中观察到联合组显著延长OS（HR=0.83；P=0.0359；mOS：12.6个月 vs 10.3个月）；在预后不良的病人分组中，联合组也能显著延长OS；联合治疗的不良事件可控制（减量或对症治疗）

Nintedanib也是一个RET抑制剂。

                               
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U.S. FDA Accepts NDA Filing for Boehringer Ingelheim’s Investigational Nintedanib and Grants Priority Review Designation for the Treatment of Idiopathic Pulmonary Fibrosis

For U.S. Media Only
Ridgefield, Conn., July 2, 2014 – Boehringer Ingelheim Pharmaceuticals, Inc. today announced that the New Drug Application (NDA) for its investigational compound nintedanib has been accepted for filing by the U.S. Food & Drug Administration (FDA) and granted Priority Review designation. The application for nintedanib is currently under review for the treatment of people with idiopathic pulmonary fibrosis (IPF), a rare, progressive and fatal lung disease that affects as many as 132,000 Americans. There are currently no FDA-approved treatments for IPF. The efficacy and safety of nintedanib in the treatment of IPF has not been established.

“This is an exciting and important next step in the review of nintedanib for the treatment of IPF, which is a serious disease with a high unmet medical need,” said Tunde Otulana, M.D., senior vice president, Clinical Development and Medical Affairs at Boehringer Ingelheim Pharmaceuticals, Inc. “If approved, nintedanib may offer a treatment option for people in the U.S. who are living with this progressive disease, and have no approved treatment options today. We look forward to continuing to work closely with the FDA during this review period.”

The FDA grants Priority Review designation for drugs that, if approved, would be significant improvements in the safety or effectiveness of the treatment of serious conditions when compared to standard applications.

The NDA package includes results from two global Phase 3 studies (INPULSIS&#8482;-1 and INPULSIS&#8482;-2) evaluating the efficacy and safety of nintedanib in the treatment of IPF. The INPULSIS&#8482; studies were recently presented at the American Thoracic Society (ATS) International Conference and published in the New England Journal of Medicine.

In June 2011, nintedanib was granted orphan-drug designation in the U.S. Orphan-drug designation is a status given to a product intended for the treatment of a rare disease or condition. In June 2013, nintedanib was then granted Fast Track designation by the FDA. The FDA's Fast Track program is designed to facilitate the development and expedite the review of drugs to treat serious conditions and fill an unmet medical need.