Epizyme’s first-in-class EZH2 (enhancer of zeste homolog 2) inhibitor Tazverik (tazemetostat) has become the first therapy to be made available in the U.S. for the treatment of epithelioid sarcoma (ES), a rare soft tissue tumor with a significant unmet need.1,2,3 The drug was granted accelerated approval in January 2020 for the treatment of patients aged 16 years and older with metastatic or locally advanced disease who are not eligible for complete resection.3 Epizyme estimates that there are roughly 800 patients living with ES in the U.S., of which approximately 300 patients could be eligible for Tazverik.4 While approval in ES is a significant milestone, Tazverik is expected to realize its full market value through use in potentially more lucrative cancer settings.
Durable efficacy in epithelioid sarcoma
Accelerated approval of Tazverik was based on clinical data from 62 patients with metastatic or locally advanced ES from the ongoing EZH-202 (NCT02601950) phase 2 trial.5,6 Although an overall response rate of only 15% was reported, among responders in the trial, 67% had a duration of response of six months or longer.6 These data compare favorably to the standard of care for soft tissue sarcoma of radiation in combination with chemotherapy, which has dose-limiting toxicities and response rates in the 12-23% range, with a median response duration of only 4.5 months.7,8,9
Epizyme is currently conducting the EZH-301 (NCT04204941) phase 3 confirmatory trial assessing the combination of Tazverik plus doxorubicin as a front-line treatment for ES. Positive data from the trial could form the basis for an additional approval in the first-line setting, expanding the potential ES market for Tazverik.10
Risk of secondary malignancies
The anticancer efficacy of Tazverik may come at a cost. The FDA placed a partial clinical hold on the development of the drug in April 2018, following a report of a patient who developed secondary T-cell lymphoma in the EZH-102 (NCT02601937) phase I pediatric trial.11,12 Although the FDA subsequently lifted the clinical hold in September 2018, a safety signal of secondary malignancy was identified.13,14 Of the 668 patients who received Tazverik in the clinical program, 0.6% developed myelodysplastic syndrome or acute myeloid leukemia, and the prescribing information for Tazverik includes a warning for the increased risk of developing secondary malignancies.14
Tazverik’s chance to shine
Although the ES patient pool is small, there is significant potential for market expansion to other more lucrative cancer settings. In December 2019, Epizyme submitted an NDA for the third-line treatment of patients with relapsed or refractory follicular lymphoma (FL), which could lead to a second approval for Tazverik this year in another patient population with unmet need.15 FL is one of 30 types of Non-Hodgkin lymphoma (NHL) and accounts for 20 to 30% of all NHL cases.16,17 Estimates suggest that the global NHL market could be worth $10.8 billion by 2025.18 The company is also planning to develop the drug in other solid tumors and hematological malignancies, as a monotherapy and combination therapy in both relapsed and front-line disease settings.15
Pricing reflects potential for market expansion
The prospects for use in larger markets have influenced Epizyme’s pricing strategy for Tazverik. The company has priced the drug at $15,500 for one-month’s supply.4,19 However, considering the ultra-rare status of ES, the price of Tazverik is relatively modest compared with the $32,800 per month cost of Bayer’s first-in-class Orphan drug Vitrakvi, which is indicated for the treatment of solid tumors with an NTRK gene fusion.20 Epizyme is playing the long game and is positioning Tazverik favorably in the market for use in other cancer settings.
While several EZH2 inhibitors are in development for the treatment of various cancers, including Constellation Pharmaceuticals’ CPI-1205 and CPI-0209, and Pfizer’s PF-06821497, development is at an early stage and first regulatory approvals are not expected until 2023.21,22,23 Tazverik therefore has the opportunity to establish itself in the market ahead of any competition from within the EZH2 inhibitor class. Strong sales growth is anticipated, with consensus forecast sales of $103 million in 2021 in its first full year on market following approval, rising to $617 million in 2024.
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