Eisai's Tazemetostat Receives Orphan Drug Designation in Japan for Rare Epithelioid Sarcoma
Key Insights
Eisai Co., Ltd. received orphan drug designation from Japan's Ministry of Health, Labour and Welfare for tazemetostat hydrobromide (Tazverik®) to treat unresectable INI1 (search)-negative epithelioid sarcoma (search) that has progressed after chemotherapy.
Epithelioid sarcoma (search) is an extremely rare soft tissue cancer accounting for only 1% of all soft tissue sarcomas, with just 174 cases registered across major Japanese hospitals over a 10-year period from 2006 to 2015.
The EZH2 (search) inhibitor targets a key molecular pathway in epithelioid sarcoma (search), where loss of INI1 (search) protein occurs in over 90% of cases, leading to EZH2 activation that drives tumor onset and malignant progression.
Eisai Co., Ltd. announced today that it has received orphan drug designation from Japan's Ministry of Health, Labour and Welfare (MHLW) for tazemetostat hydrobromide (Tazverik® Tablets 200 mg), an EZH2 (search) inhibitor, for the treatment of unresectable INI1 (search)-negative epithelioid sarcoma (search) that has progressed after chemotherapy.
Addressing an Ultra-Rare Cancer with Limited Treatment Options
Epithelioid sarcoma (search) represents one of the rarest forms of soft tissue sarcoma (search), estimated to account for approximately 1% of all soft tissue sarcomas. The extreme rarity of this cancer is underscored by Japanese registry data showing only 174 cases registered from major hospitals across the country over a 10-year period from 2006 to 2015.
The disease presents significant therapeutic challenges due to limited treatment options, resulting in what Eisai describes as "an extremely high unmet medical need." The molecular characteristics of epithelioid sarcoma (search) provide insight into potential therapeutic targets, with loss of INI1 (search) protein observed in over 90% of cases.
Targeting the EZH2 Pathway
Tazemetostat's mechanism of action centers on inhibiting EZH2 (search), a histone methyltransferase enzyme that controls gene expression by methylating the 27th lysine residue of histone H3 (H3K27). In epithelioid sarcoma (search), the loss of INI1 (search)—a negative regulator of EZH2 and a component of the SWI/SNF chromatin remodeling complex—leads to EZH2 activation that is believed to drive tumor onset and malignant progression.
INI1 (search) normally functions as part of the SWI/SNF chromatin complex, a protein complex that modifies chromatin structure to regulate gene function and is involved in controlling gene expression. When INI1 is lost, this regulatory mechanism is disrupted, allowing unchecked EZH2 (search) activity.
Clinical Development and Regulatory History
Tazemetostat previously received approval in Japan in June 2021 for relapsed or refractory EZH2 (search) gene mutation-positive follicular lymphoma (search), specifically when standard treatment is not applicable. This earlier approval established the drug's safety profile and regulatory pathway in Japan.
For the epithelioid sarcoma (search) indication, clinical evidence is being generated through the TAZETTA trial (A Phase II Trial of Tazemetostat for Patients with Unresectable or Metastatic Epithelioid Sarcoma), a Phase II investigator-initiated study led by the National Cancer Center Hospital that is currently underway.
Strategic Focus on Oncology
Eisai has identified oncology as one of its priority therapeutic areas, with the company stating its commitment to "develop ground breaking new therapies aimed at curing cancer." The orphan drug designation for tazemetostat in epithelioid sarcoma (search) aligns with this strategic focus and represents the company's efforts to address rare cancers with significant unmet medical needs.
The company emphasized its ongoing commitment "to meeting the diverse needs of cancer patients worldwide, their families, and healthcare professionals, and to enhancing the benefits delivered to them."