Pexidartinib: First Approval
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Pexidartinib (TURALIO™) is an orally administered small molecule tyrosine kinase inhibitor with selective activity against the colony-stimulating factor 1 (CSF1) receptor, KIT proto-oncogene receptor tyrosine kinase (KIT) and FMS-like tyrosine kinase 3 harboring an internal tandem duplication mutation (FLT3-ITD). In August 2019, the US FDA approved pexidartinib capsules for the treatment of adult patients with symptomatic tenosynovial giant cell tumor (TGCT) associated with severe morbidity or functional limitations and not amenable to improvement with surgery. This approval was based on positive results from the phase III ENLIVEN trial. Pexidartinib is being investigated in various malignancies as monotherapy or combination therapy. This article summarizes the milestones in the development of pexidartinib leading to its first approval for TGCT.
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. Yvette Lamb is a salaried employee of Adis International Ltd/Springer Nature, is responsible for the article content and declares no relevant conflicts of interest.
- 9.Daiichi Sankyo Inc. TURALIOTM (pexidartinib) capsules, for oral use: US prescribing information 2019. http://www.accessdata.fda.gov/. Accessed 30 Sep 2019.
- 12.Food and Drug Administration. FDA approves first therapy for rare joint tumor [media release]. 2 Aug 2019. http://www.fda.gov.
- 17.Vandell AG, Duchin KL, Desai M, et al. Effect of dose strength, food, and pH modifiers on the pharmacokinetics of the multi-kinase inhibitor pexidartinib [abstract no. PI-152]. Clin Pharmacol Ther. 2018;103(Suppl S1):S54.Google Scholar
- 18.Daiichi Sankyo Inc. Briefing document for the May 14, 2019, US FDA oncologic drugs advisory committee meeting: Turalio (pexidartinib) capsules. 2019. http://www.fda.gov/. Accessed 30 Sep 2019.
- 19.Gelderblom H, Tap WD, Palmerini E, et al. Pexidartinib for advanced tenosynovial giant cell tumor (TGCT): long-term efficacy and safety from the phase 3 ENLIVEN and phase 1 PLX108-01 (TGCT cohort) studies [abstract no. 11042]. J Clin Oncol. 2019;37(Suppl 15):11042.Google Scholar
- 22.Manji GA, Van Tine BA, Lee SM, et al. Phase 1 combination therapy with pexidartinib (PEX) and sirolimus (S) to target tumor-associated macrophages in pigmented villonodular synovitis, malignant peripheral nerve sheath tumors, and other soft tissue sarcomas [abstract no. 11055]. J Clin Oncol. 2019;37(Suppl 15):11055.Google Scholar
- 24.Wagner AJ, Tap WD, Shields AF, et al. A phase I pharmacokinetic (PK) and pharmacodynamic (PD) study of PLX9486 alone and in combination (combo) with the KIT inhibitors pexidartinib (pexi) or sunitinib (su) in patients (Pts) with advanced solid tumors and gastrointestinal stromal tumor (GIST) [abstract no. 11509]. J Clin Oncol. 2018;36(Suppl 15):11509.CrossRefGoogle Scholar
- 28.Daiichi Sankyo Company. ENLIVEN phase 3 study of pexidartinib in tenosynovial giant cell tumor (TGCT) will continue to completion following enrollment discontinuation [media release]. 21 Oct 2016. http://www.daiichisankyo.com.
- 29.Bauer S, Lewis JH, Gelderblom H, et al. Pexidartinib for locally advanced tenosynovial giant cell tumor (TGCT): characterization of hepatic adverse reactions (ARs) [poster no. 1696P]. In: ESMO 2019.Google Scholar