Tazemetostat: First Approval

Our plain-English summary of Tazemetostat: First Approval, by S.M. Hoy (Drugs, 2020).

The study

• Author: S.M. Hoy
• Journal: Drugs
• Published: 2020;80(5):513-521
• Type of article: Review
• Cited by: 288 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Tazemetostat (Tazverik™), a first-in-class, small molecule enhancer of zeste homolog 2 (EZH2) inhibitor, received accelerated approval in January 2020 in the USA for the treatment of adults and adolescents aged ≥ 16 years with locally advanced or metastatic epithelioid sarcoma not eligible for complete resection. Developed by Epizyme, in collaboration with Eisai, it is the first therapy to be approved specifically for the treatment of epithelioid sarcoma in the USA. The recommended dosage regimen is 800 mg twice daily, administered orally with or without food, until disease progression or unacceptable toxicity. Tazemetostat is also undergoing clinical development in various countries worldwide for use in several other tumour types, including diffuse large B-cell lymphoma and mesothelioma, with the US FDA accepting a New Drug Application and granting priority review for its use in the treatment of follicular lymphoma. This article summarizes the milestones in the development of tazemetostat leading to this first approval for the treatment of adults and adolescents aged ≥ 16 years with locally advanced or metastatic epithelioid sarcoma not eligible for complete resection.

In plain English

This article was a drug profile review, not a study of asbestos exposure. It was written by one author and drawn from the AdisInsight drug development database. It summarized the development of tazemetostat, an oral drug that blocks an enzyme called EZH2, up to its first approval in the USA on 23 January 2020. That approval covered adults and adolescents aged 16 years or older with locally advanced or metastatic epithelioid sarcoma not eligible for complete resection. The recommended dose was 800 mg twice daily. In the 62-patient epithelioid sarcoma group whose results the approval was based on, 15% responded. The review also described a phase II study (EZH-203), cited from a conference abstract, of 61 adults with relapsed or refractory malignant mesothelioma with inactive BAP1. In that study, 51% had disease control at 12 weeks, 15 (25%) had sustained disease control at 24 weeks, and two had a confirmed partial response. The drug had orphan designation for mesothelioma in the USA and EU. In a pooled safety group of 725 patients, secondary blood cancers were reported in 0.8%.

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 profile review (AdisInsight Report) summarizing development milestones and published or presented trial data for tazemetostat; no original study
• Who was studied: No study population of its own. The review summarized clinical trials of tazemetostat in patients with several cancers, including the 62-patient epithelioid sarcoma group from the phase II EZH-202 study and 61 adults with relapsed or refractory malignant mesothelioma in the phase II EZH-203 study
• Exposure: The drug tazemetostat (an EZH2 inhibitor), recommended at 800 mg twice daily by mouth. No asbestos or fiber exposure was studied
• Main results:
  • Tazemetostat received its first approval in the USA on 23 January 2020, for locally advanced or metastatic epithelioid sarcoma not eligible for complete resection
  • In the 62-patient epithelioid sarcoma group of EZH-202, the overall response rate was 15%
  • In 61 adults with relapsed or refractory malignant mesothelioma with inactive BAP1 (EZH-203), the disease control rate at 12 weeks was 51%
  • In the same mesothelioma study, 15 (25%) patients had sustained disease control at 24 weeks
  • Secondary myelodysplastic syndrome, acute myeloid leukaemia or T-cell lymphoblastic lymphoma were reported in 0.8% of 725 adult and paediatric patients in a pooled safety population
  • The review reported that tazemetostat received orphan designation for mesothelioma in the USA in September 2017 and in the EU in May 2018
• The authors' conclusion: The author gave no overall conclusion. The article ended by restating the first US approval for epithelioid sarcoma. The author also described the drug's safety profile as favourable when used alone, and noted that a phase III study (EZH-301) had been started to support full approval for epithelioid sarcoma.

Topics

Medical terms in this study, explained in our Lexicon: Epithelioid, Sarcoma, Disease Progression, Mesothelioma.

Related studies

• Nintedanib: first global approval — P.L. McCormack (2015)
• A first-in-Asian phase 1 study to evaluate safety, pharmacokinetics and clinical activity of VS-6063, a focal adhesion kinase (FAK) inhibitor in Japanese patients with advanced solid tumors — T. Shimizu, K. Fukuoka, et al. (2016)
• A phase II trial of single oral FGF inhibitor, AZD4547, as second or third line therapy in malignant pleural mesothelioma — W.S. Lam, J. Creaney, et al. (2020)
• Epithelioid sarcoma. A clinical and pathologic study of nine cases — H. Santiago, L.K. Feinerman, et al. (1972)
• Diagnostic utility of BAP1 and EZH2 expression in malignant mesothelioma — A. Shinozaki-Ushiku, T. Ushiku, et al. (2017)
• Highly expressed EZH2 in combination with BAP1 and MTAP loss, as detected by immunohistochemistry, is useful for differentiating malignant pleural mesothelioma from reactive mesothelial hyperplasia — M. Yoshimura, Y. Kinoshita, et al. (2019)

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