Nintedanib: first global approval

Our plain-English summary of Nintedanib: first global approval, by P.L. McCormack (Drugs, 2015).

The study

• Author: P.L. McCormack
• Journal: Drugs
• Published: 2015;75(1):129-39
• Cited by: 97 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Nintedanib (Ofev(®)) is an orally available, small, multiple receptor tyrosine kinase inhibitor developed by Boehringer Ingelheim for the treatment of idiopathic pulmonary fibrosis (IPF) and cancer. Nintedanib received its first global approval in the US in October 2014 for the treatment of IPF. Nintedanib has received a positive opinion from the European Medicines Agency's Committee for Medicinal Products for Human Use for the treatment of IPF, and for the second-line treatment in combination with docetaxel of locally advanced, metastatic or locally recurrent non-small cell lung cancer of adenocarcinoma tumour histology. Phase 3 development programmes are also underway for colorectal cancer and ovarian cancer. Phase 2 investigation is being conducted for a variety of other solid tumours, including hepatocellular carcinoma, mesothelioma, prostate cancer, glioblastoma, renal cell carcinoma and endometrial cancer. This article summarizes the milestones in the development of nintedanib leading to this first approval for IPF.

In plain English

This article was a drug development profile, not an original study. It was drawn from the Adis R&D Insight drug pipeline database. It reviewed the development of nintedanib up to its first approval, in the US on 15 October 2014, for idiopathic pulmonary fibrosis (IPF). It did not study asbestos exposure. The US approval was based on 1,231 patients in two phase 3 trials and one phase 2 trial. The author reported, from those trials, that nintedanib reduced the yearly decline in forced vital capacity (FVC) compared with placebo by 52% in INPULSIS-1 (minus 114.7 versus minus 239.9 mL per year) and by 45% in INPULSIS-2 (minus 113.6 versus minus 207.3 mL per year). Across the three IPF trials, diarrhoea occurred in 62% of nintedanib recipients versus 18% on placebo. Treatment was stopped because of adverse events by 21% versus 15%. Mesothelioma appeared only as a recruiting phase 2 trial of nintedanib plus pemetrexed and cisplatin, followed by maintenance nintedanib, in unresectable malignant pleural mesothelioma, with no results given. The author stated that nintedanib was the first tyrosine kinase inhibitor approved for IPF.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Drug development profile (review), extracted and modified from the Adis R&D Insight drug pipeline database; not an original study
• Who was studied: No population of its own. The review summarised published and ongoing trials of nintedanib. The US approval for IPF rested on 1,231 patients in two phase 3 trials (INPULSIS-1 and INPULSIS-2) and one phase 2 trial (TOMORROW).
• Exposure: No asbestos or fiber exposure was studied. The subject was the drug nintedanib, approved for IPF at an oral dosage of 150 mg twice daily.
• Main results:
  • Nintedanib received its first global approval on 15 October 2014 in the USA, for IPF
  • In the INPULSIS-1 trial (as reported in the review), nintedanib reduced the annual decline in forced vital capacity (FVC, the primary endpoint) by 52% compared with placebo (-114.7 vs. -239.9 mL/year)
  • In the INPULSIS-2 trial (as reported in the review), the reduction in annual FVC decline was 45% (-113.6 vs. -207.3 mL/year)
  • Across the three IPF trials, diarrhoea occurred in 62% of nintedanib recipients vs. 18% with placebo
  • 21% of nintedanib recipients vs. 15% of placebo recipients discontinued therapy because of adverse events
  • Mesothelioma appeared only as a recruiting, multinational phase 2 trial of nintedanib plus pemetrexed/cisplatin (followed by maintenance nintedanib, per the cited trial title) in unresectable malignant pleural mesothelioma (NCT01907100); no results were reported
• The authors' conclusion: The author stated that nintedanib is the first tyrosine kinase inhibitor approved for IPF

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer.

Medical terms in this study, explained in our Lexicon: Tyrosine Kinase Inhibitor, Idiopathic, Pulmonary Fibrosis, Non-Small Cell Lung Cancer, Adenocarcinoma, Histology, Colorectal Cancer, Ovarian Cancer.

Related studies

• Nintedanib in combination with pemetrexed and cisplatin for chemotherapy-naive patients with advanced malignant pleural mesothelioma (LUME-Meso): a double-blind, randomised, placebo-controlled phase 3 trial — G.V. Scagliotti, R. Gaafar, et al. (2019)
• Tazemetostat: First Approval — S.M. Hoy (2020)
• SU6668, a multiple tyrosine kinase inhibitor, inhibits progression of human malignant pleural mesothelioma in an orthotopic model — T.T. Van, M. Hanibuchi, et al. (2012)
• Cediranib in patients with malignant mesothelioma: a phase II trial of the University of Chicago Phase II Consortium — N.P. Campbell, R. Kunnavakkam, et al. (2012)
• Radiological characteristics, histological features and clinical outcomes of lung cancer patients with coexistent idiopathic pulmonary fibrosis — K.A. Khan, M.P. Kennedy, et al. (2015)
• Antifibrotic treatment response and prognostic predictors in patients with idiopathic pulmonary fibrosis and exposed to occupational dust — V. Casillo, S. Cerri, et al. (2019)

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