Immune checkpoint inhibitors (ICI): An analysis of FDA’s and EMA’s decision patterns and times for initial approvals and extensions of indication.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14062-e14062 ◽  
Author(s):  
Christine Mayer-Nicolai ◽  
Elmar Schmitt ◽  
Markus Hartmann ◽  
Philippe Serrano
Keyword(s):  
Checkpoint Inhibitors ◽  
Regulatory Approval ◽  
European Medicines Agency ◽  
Priority Review ◽  
Marketing Approval ◽  
Cancer Drugs ◽  
Line Extensions ◽  
The Us ◽  
The Usa ◽  
Us Fda

e14062 Background: In certain clinical settings ICI have demonstrated unprecedented patterns of efficacy, resulting since 2011 in regulatory approvals worldwide in a variety of cancer indications. As immuno-oncology (IO) drugs constitute today an intense area of oncology drug development, we sought to analyze and compare the regulatory approval decisions for ICI, issued until end of 2018 by the US FDA and the European Medicines Agency (EMA). Methods: We reviewed the biological license applications (BLA) of the 7 (EU: 6) ICI, for which marketing approval decisions for were granted so far. Together with parallel and extension of indication applications, 43 (FDA) respectively 23 (EMA) approval procedures were finalized between March 2011 and December 2018. We analyzed agency decision outcomes and timeline patterns; approval decisions issued for novel non-IO cancer drugs served as benchmarks. The primary variable for analysis was median approval time (MAT). Results: MAT for initial BLA applications for ICI in the USA were with 189 days [Interquartile range (IQR) 154-209] shorter than MAT for BLA and NDA approvals for non-IO drugs: for the 51 novel oncology drugs approved 2011-2018 by the FDA, MAT was 227 days [IQR 159-303]. With 181 days [IQR 155-184], FDA’s MAT for ICI line extensions did not differ from MAT for initial ICI approvals. For the EU, MAT for initial ICI marketing applications were with 373 days (IQR 326-413) also shorter than MAT for the 51 non-IO drugs approved 2011-18 (422 days [IQR 368-450]); for ICI line extensions, MAT was 254 days [IQR 187-293). Conclusions: For ICI as for novel non-IO cancer drugs, initial regulatory approvals are usually issued in the USA first. Regulatory approval times for initial approvals are shorter in the USA, compared to Europe, the same applies for ICI extensions of indication. FDA’s extensive granting of breakthrough therapy designations (BTD) helped to bring US MAT for initial ICI BLA down to 6 months – i.e. to the same time, FDA requires for its priority review of extensions of indication. For some ICI extensions of indication, the granting of BTD supported approval decisions within 3 months, supporting patients’ rapid access to novel therapies.

scholarly journals Lessons From the Development of the Immune Checkpoint Inhibitors in Oncology

2018 ◽  
Vol 17 (4) ◽  
pp. 1012-1015 ◽  
Author(s):  
Denis L. Jardim ◽  
Débora de Melo Gagliato ◽  
Razelle Kurzrock
Keyword(s):  
Phase I ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Dose Finding ◽  
Priority Review ◽  
Marketing Approval ◽  
Phase I Trials ◽  
Clinical Cancer Research ◽  
Number Of Patients

Immunotherapies are becoming increasingly important in the treatment armamentarium of a variety of malignancies. Immune checkpoint inhibitors are the most representative drugs receiving regulatory approval over the past few years. In a recent study published in Clinical Cancer Research, we demonstrated that these agents are being developed faster than other prior anticancer therapies. All checkpoint inhibitors received priority review, being granted with at least one Food and Drug Administration expedited program. Hence, some of them are getting marketing approval after preliminary trials. The model continues to rely on phase I trials, designed with traditional models for dose definition, although a substantial number of patients are treated during the dose expansion cohorts. We demonstrated that efficacy and safety are reasonably predicted from the dose-finding portion of phase I trials with these agents, assuring a low treatment-related mortality for patients throughout the development process. In this article, we further discuss and summarize these findings and update some recent approval information for immune checkpoint inhibitors.

scholarly journals UHPLC–MS/MS method for iohexol determination in human EDTA and lithium-heparin plasma, human urine and in goat- and pig EDTA plasma

Bioanalysis ◽  
2020 ◽  
Vol 12 (14) ◽  
pp. 981-990
Author(s):  
Jasper Stevens ◽  
Mireille A Wessels ◽  
Jan Roggeveld ◽  
Remco A Koster ◽  
Claire CJ Dekkers ◽  
...  
Keyword(s):  
Human Urine ◽  
Pharmacokinetic Profile ◽  
European Medicines Agency ◽  
Simple Method ◽  
The Us ◽  
Heparin Plasma ◽  
Thermo Fisher Scientific ◽  
Tandem Quadrupole Mass Spectrometer ◽  
Edta Plasma ◽  
Us Fda

Aim: Iohexol plasma clearance is used as an indicator of kidney function in clinical and preclinical settings. To investigate the pharmacokinetic profile of iohexol, a rapid, simple method for measurement of iohexol in different matrices and species was needed. Materials & methods: Iohexol was separated on an Accucore C18 column (Thermo Fisher Scientific, CA, USA). Detection was performed on a Thermo Scientific Quantiva tandem quadrupole mass spectrometer. The method was validated according to the requirements for bioanalytical methods issued by the US FDA and European Medicines Agency. Conclusion: We developed and validated a fast and efficient analytical method, suitable for analyzing iohexol in human EDTA plasma, human lithium-heparin plasma, human urine and goat- and pig EDTA plasma, using only one calibration line prepared in human EDTA plasma.

Japan’s conditional early approval program for innovative cancer drugs: Comparison of the regulatory processes with the US FDA and the EMA

Cancer Cell ◽  
2021 ◽  
Author(s):  
Anju Murayama ◽  
Munetaka Ueda ◽  
Sunil Shrestha ◽  
Tetsuya Tanimoto ◽  
Akihiko Ozaki
Keyword(s):  
Cancer Drugs ◽  
Regulatory Processes ◽  
The Us ◽  
Us Fda

scholarly journals Structural and Functional Characterization of Low-molecular-weight Heparins: Impact on the Development of Guidelines for Generic Products

2009 ◽  
Vol 15 (2) ◽  
pp. 137-144 ◽  
Author(s):  
Cafer Adiguzel ◽  
Walter P. Jeske ◽  
Debra Hoppensteadt ◽  
Jeanine M. Walenga ◽  
Vinod Bansal ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Functional Characterization ◽  
Current Data ◽  
European Medicines Agency ◽  
Low Molecular Weight ◽  
Low Molecular Weight Heparins ◽  
Biological Drugs ◽  
Biologic Drugs ◽  
The Us ◽  
Us Fda

Low-molecular-weight heparins (LMWHs) are poly-pharmacologic drugs used to treat thrombotic and cardiovascular disorders. Recently, several generic versions of branded LMWHs have been introduced. Although generic versions of LMWHs exhibit similar profiles, marked differences in their biological and pharmacologic properties have been demonstrated. Several studies have demonstrated differences in terms of anti-Xa activity and tissue factor pathway inhibitor release. The current data emphasize the need to consider multiple functional parameters when defining bioequivalence of biologic drugs and also underscore the importance of further pharmacologic studies involving animal and human clinical trials. The US Food and Drug Administration (FDA) and the European Medicines Agency (EMEA) are currently developing guidelines for the acceptance of complex biological drugs including LMWHs. The US FDA considers these drugs as follow-on agents whereas the EMEA classifies these drugs as biosimilar agents. Until clear guidelines are developed, generic interchange of LMWHs may not be feasible.

scholarly journals Small molecules in targeted cancer therapy: advances, challenges, and future perspectives

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Lei Zhong ◽  
Yueshan Li ◽  
Liang Xiong ◽  
Wenjing Wang ◽  
Ming Wu ◽  
...  
Keyword(s):  
Small Molecule ◽  
Kinase Inhibitor ◽  
Cancer Drugs ◽  
Drug Candidates ◽  
Chemotherapy Drugs ◽  
National Medical ◽  
Anti Cancer ◽  
The Us ◽  
Us Fda ◽  
Approved Drugs

AbstractDue to the advantages in efficacy and safety compared with traditional chemotherapy drugs, targeted therapeutic drugs have become mainstream cancer treatments. Since the first tyrosine kinase inhibitor imatinib was approved to enter the market by the US Food and Drug Administration (FDA) in 2001, an increasing number of small-molecule targeted drugs have been developed for the treatment of malignancies. By December 2020, 89 small-molecule targeted antitumor drugs have been approved by the US FDA and the National Medical Products Administration (NMPA) of China. Despite great progress, small-molecule targeted anti-cancer drugs still face many challenges, such as a low response rate and drug resistance. To better promote the development of targeted anti-cancer drugs, we conducted a comprehensive review of small-molecule targeted anti-cancer drugs according to the target classification. We present all the approved drugs as well as important drug candidates in clinical trials for each target, discuss the current challenges, and provide insights and perspectives for the research and development of anti-cancer drugs.

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