Fedratinib: First Approval
Fedratinib (INREBIC®) is a JAK2-selective inhibitor that has been developed as an oral treatment for myelofibrosis. In August 2019, fedratinib received its first global approval in the USA for the treatment of adult patients with intermediate-2 or high-risk primary or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis. Phase III clinical development for myelofibrosis is ongoing worldwide. This article summarizes the milestones in the development of fedratinib leading to this first approval for myelofibrosis.
Compliance with Ethical Standards
The preparation of this review was not supported by any external funding.
Conflicts of interest
During the peer review process the manufacturer of the agent under review was offered an opportunity to comment on the article. Changes resulting from any comments received were made by the author on the basis of scientific completeness and accuracy. Hannah A. Blair is a salaried employee of Adis International Ltd/Springer Nature, is responsible for the article content and declares no relevant conflicts of interest.
- 4.Celgene Corporation. INREBIC® (fedratinib) capsules, for oral use: US prescribing information. 2019. http://www.fda.gov/. Accessed 16 Aug 2019.
- 5.Celgene Corporation. U.S. FDA approves INREBIC® (fedratinib) as first new treatment in nearly a decade for patients with myelofibrosis [media release]; 16 Aug 2019. http://ir.celgene.com.
- 6.US FDA. FDA approves fedratinib for myelofibrosis. 2019. http://www.fda.gov. Accessed 27 Aug 2019.
- 7.TargeGen Inc. Sanofi-Aventis to acquire TargeGen, Inc [media release]; 1 July 2010. http://www.targegen.com.
- 8.Impact Biomedicines. Startup Impact Biomedicines raises $22M to bring fedratinib to myelofibrosis patients [media release]; 16 Oct 2017. http://www.impactbiomedicines.com.
- 9.Impact Biomedicines. Impact Biomedicines closes $90 million financing with Oberland Capital to fund fedratinib program advancement [media release]; 27 Oct 2017. http://www.impactbiomedicines.com.
- 10.Celgene Corporation, Impact Biomedicines. Celgene to acquire Impact Biomedicines, adding fedratinib to its pipeline of novel therapies for hematologic malignancies [media release]; 8 Jan 2018. http://www.celgene.com.
- 14.Kittur J, Lasho TL, Butterfield JH, et al. TG101348, an orally bioavailable JAK2-selective inhibitor, potently inhibits KITD816V and FIP1L1-PDGFRA in vitro [abstract no. 2807]. Blood. 2008;112(11):2807.Google Scholar
- 15.Olnes MJ, Poon A, Tucker Z, et al. JAK2 inhibition with TG101348 inhibits monosomy 7 myelodysplastic syndromes (MDS) bone marrow cells in vitro: a potential targeted therapy for monosomy 7 MDS [abstract no. 973]. Blood. 2010;116(21):973.Google Scholar
- 17.Hood J, Hazell A. Fedratinib does not inhibit thiamine uptake or induce experimental Wernicke’s encephalopathy in nonclinical studies [abstract no. 4993]. Blood. 2017;130(Suppl 1):4993.Google Scholar
- 18.Greco R, Hurley R, Sun F, et al. SAR302503: a Jak2 inhibitor with antitumor activity in solid tumor models [abstract no. 1796]. Cancer Res. 2012;72(8 Suppl 1):1796.Google Scholar
- 19.Gotlib J, Pardanani A, Jamieson C, et al. Long-term follow up of a phase 1/2 study of SAR302503, an oral JAK2 selective inhibitor, in patients with myelofibrosis (MF) [abstract no. 0361]. Haematologica. 2012;97(Suppl 1):0361.Google Scholar
- 25.Xu C, Shamiyeh E, Kanamaluru V, et al. A gastric PH modifier pantoprazole did not significantly affect the on pharmacokinetics of fedratinib in healthy male subjects [abstract no. PI-085]. Clin Pharmacol Ther. 2015;97(Suppl 1):PI-085.Google Scholar
- 29.Harrison C, Schaap N, Vannucchi A, et al. Fedratinib in patients with myeloproliferative neoplasm (MPN)-associated myelofibrosis (MF) previously treated with ruxolitinib (RUX): a reanalysis of the phase 2 JAKARTA-2 study [abstract no. PS1459 plus poster]. In: 24th Annual Congress of the European Hematology Association. 2019.CrossRefGoogle Scholar
- 30.Sanofi. Sanofi discontinues clinical development of investigational JAK2 agent fedratinib (SAR302503) [media release]; 18 Nov 2013. http://en.sanofi.com.
- 31.Verstovsek S, Harrison CN, Barosi G, et al. FREEDOM: a phase 3b efficacy and safety study of fedratinib in intermediate- or high-risk myelofibrosis patients previously treated with ruxolitinib [abstract no. TPS7072]. J Clin Oncol. 2019;37(Suppl 15):TPS7072.Google Scholar