Tazemetostat Granted Orphan Drug Status by FDA for Soft Tissue Sarcoma


The FDA has granted orphan drug designation to its EZH2-inhibitor tazemetostat for the treatment of adults with INI1-negative epithelioid sarcoma, Epizyme has announced.

Robert Bazemore

Robert Bazemore

The FDA has granted orphan drug designation to its EZH2-inhibitor tazemetostat for the treatment of adults with INI1-negative epithelioid sarcoma, Epizyme has announced.

The designation gives the company market exclusivity for soft tissue sarcomas beyond Epizyme’s intellectual property protection and grants access to certain development incentives. The orphan drug designation program is reserved for the safe and effective treatment, diagnosis, or prevention of conditions that affect fewer than 200,000 people in the United States

Epithelioid sarcomas are rare, mesenchymal tumors of unknown histogenesis that account for less than 1% of all soft tissue sarcomas. These tumors are usually slow growing, occur predominantly in extremities, and appear most often in young adult men.1

Median overall survival is roughly 88 months for patients with local metastases and just 8 months for those with distant metastases.1

In 1 study, 93% of epithelioid sarcomas, both conventional and proximal-type, were negative for INI1 expression.2

“This is an important milestone for Epizyme as we advance tazemetostat through clinical development,” company president and CEO Robert Bazemore said in a statement. “We are encouraged by the positive regulatory milestones we have achieved for tazemetostat, including this orphan drug designation for soft tissue sarcomas.”

The company supported its application with preliminary phase II data presented at the 2017 ASCO Annual Meeting.3Fifteen patients were included in phase I.

In this second phase of the open-label, single-arm study, 31 patients were treated with 800 mg of tazemetostat in continuous 28-day cycles until progression, unacceptable toxicity, withdrawal, or study termination.

Tumor response was evaluated every 8 weeks. Disease control rate (DCR), defined as objective response of any duration or stable disease lasting ≥32 weeks, was the primary endpoint. Success at stage 2 required DCR in at least 5 of 30 treated patients.

Fifteen patients (48%) had distal tumors. The remaining tumors were proximal.

Median progression-free survival was 5.7 months. DCR was 10% with a confirmed response rate of 13% and a stable disease rate of 19% at ≥32 weeks. Seven patients (23%) had disease progression.

Best overall response was partial response (13%), and there were no complete responses recorded. Thirteen patients remain on treatment, and DCR and ORR outcomes will be updated as the data matures.

The company plans to enroll another 30 patients based on objective response observed in this initial cohort.

Twenty-four patients (77%) experienced adverse events (AEs). Grade 1/2 fatigue (42%), nausea (26%), decreased appetite (26%) and vomiting (19%) were the most common AEs of any grade. The most common grade ≥3 AEs (≥10%) were anemia (13%), dyspnea (10%), and pleural effusion (10%). There were no dose reductions or discontinuations recorded. Three patients (10%) died due to progression.

Currently, investigators are also conducting ongoing phase II studies of tazemetostat in follicular lymphoma, diffuse large B-cell lymphoma, mesothelioma, and certain molecularly defined solid tumors, including epithelioid sarcoma and other INI1-negative tumors.

The FDA in April granted fast track status to tazemetostat for the treatment of patients with relapsed or refractory follicular lymphoma, either wild type EZH2 or with EZH2 activating mutations. The agency granted the drug Fast Track status in 2016 for patients with relapsed/refractory diffuse large B-cell lymphoma withEZH2-activating mutations.


  1. Armah HB, Parwani AV. Arch Pathol Lab Med. 2009;133:814-819.
  2. Lin G, Doyle LA. Arch Pathol Lab Med. 2015;139:106-121.
  3. Gounder MM, Stacchiotti S, Schöffski P, et al. Phase 2 multicenter study of the EZH2 inhibitor tazemetostat in adults with INI1 negative epithelioid sarcoma (NCT02601950).J Clin Oncol.35, 2017 (suppl; abstr 11058).
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