CAMBRIDGE, Mass.--(BUSINESS WIRE) - Jan. 23, 2020 -- Epizyme, Inc. (Nasdaq: EPZM), a biopharmaceutical company developing novel epigenetic therapies, today announced that the U.S. Food and Drug Administration (FDA) has granted accelerated approval of Tazverik (tazemetostat) for the treatment of adults and pediatric patients aged 16 years and older with metastatic or locally advanced epithelioid sarcoma not eligible for complete resection, based on overall response rate and duration of response in a Phase 2 clinical trial.

“Despite industry advancements, there are limited therapeutic options for treating patients with epithelioid sarcoma who struggle with high rates of recurrence and toxicities associated with currently used therapies,” said Gary K. Schwartz, M.D., chief of hematology and oncology at Columbia University and NewYork-Presbyterian Hospital, deputy director of the Herbert Irving Comprehensive Cancer Center, professor of oncology at Columbia University Vagelos College of Physicians and Surgeons and an investigator in Epizyme’s Phase 2 trial. “The Tazverik data from the ES cohort in Epizyme’s Phase 2 trial support its potential to provide clinically meaningful and durable responses, and tolerability for ES patients. This approval of Tazverik represents an important advancement in the treatment of patients with ES.”

“Today’s accelerated approval of Tazverik is a landmark event for people with ES and represents our dedication to our mission of rewriting treatment for people with cancer and other serious diseases,” said Robert Bazemore, president and chief executive officer of Epizyme. “Tazverik is now the first and only FDA-approved EZH2 inhibitor, and the first and only FDA-approved treatment specifically indicated for ES patients. Our commercial launch plans are underway, and we expect to make Tazverik available to ES patients and treating physicians across the U.S. within 10 business days.”

“For people with epithelioid sarcoma, an aggressive life threatening cancer that affects young adults, having new treatment options can offer much needed hope,” added Denise Reinke, MS, NP, MBA, president and chief executive officer of the Sarcoma Alliance for Research through Collaboration (SARC) and co-founder of the Sarcoma Coalition.

Dr. Shefali Agarwal, chief medical officer, commented, “Discovering, developing and obtaining FDA approval for Tazverik, with its novel mechanism of action, is the result of years of work and commitment by many people, including the patients, caregivers and physicians who have participated in our clinical trials, along with the talented team at Epizyme. We are tremendously proud of this important milestone and look forward to further advancing clinical development of tazemetostat for multiple types of cancers.”

Continued approval for this indication is contingent upon verification and description of clinical benefit in a confirmatory trial. The company’s ongoing, global, randomized, controlled confirmatory trial assessing the combination of Tazverik plus doxorubicin compared with doxorubicin plus placebo as a front-line treatment for ES is underway.

In addition, Epizyme will conduct certain post-marketing activities, including clinical pharmacology evaluations to assess the effect of Tazverik on liver function and the effect of CYP3A inhibitors and inducers on Tazverik to inform aspects of the prescribing information. The company will also expand enrollment in Cohort 6 of its Phase 2 study, which has enrolled 44 patients to date, for a total of at least 60 epithelioid sarcoma patients. This expansion is intended to provide more patient experience for potential future inclusion in the label.

Phase 2 Epithelioid Sarcoma Cohort Efficacy Data
The efficacy of Tazverik was evaluated in an open-label, single-arm cohort (Cohort 5) of a multi-center study (Study EZH-202, NCT02601950) in patients with histologically confirmed, metastatic or locally advanced epithelioid sarcoma. Patients were required to have INI1 loss, detected using local tests, and an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-2. Patients received Tazverik 800 mg orally twice daily until disease progression or unacceptable toxicity. Tumor response assessments were performed every 8 weeks. The major efficacy outcome measures were confirmed overall response rate (ORR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as assessed by blinded independent central review (BICR) and duration of response (DOR). Median duration of follow-up was 14 months (range 0.4 to 31).

Among the 62 patients who received Tazverik, median age was 34 years (range 16 to 79); 63% were male, 76% were White, 11% were Asian, 44% had proximal disease, 92% had an ECOG PS of 0 or 1, and 8% had an ECOG PS of 2. Prior surgery occurred in 77% of patients; 61% received prior systemic chemotherapy.

In the total 62 patients treated, the ORR (95% confidence interval) was 15% (7%, 26%), with 1.6% of patients achieving a complete response and 13% achieving a partial response. Among responders in the trial, 67% had a duration of response of six months or longer.

Serious adverse reactions occurred in 37% of patients receiving Tazverik. Serious adverse reactions in ≥3% of patients who received Tazverik were hemorrhage, pleural effusion, skin infection, dyspnea, pain, and respiratory distress.

One patient (2%) permanently discontinued Tazverik due to an adverse reaction of altered mood.

Dosage interruptions due to an adverse reaction occurred in 34% of patients who received Tazverik. The most frequent adverse reactions requiring dosage interruptions in ≥3% were hemorrhage, increased alanine aminotransferase (ALT), and increased aspartate aminotransferase (AST).

Dose reduction due to an adverse reaction occurred in one (2%) patient who received Tazverik; the dose was reduced in this patient for decreased appetite.

The most common adverse reactions (≥20%) were pain, fatigue, nausea, decreased appetite, vomiting and constipation.

View the U.S. Full Prescribing Information here: Epizyme.com

About Tazverik

Tazverik is a methyltransferase inhibitor indicated for the treatment of adults and pediatric patients aged 16 years and older with metastatic or locally advanced epithelioid sarcoma not eligible for complete resection. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

Dosage and Administration

The recommended dosage of Tazverik is 800 mg taken orally twice daily with or without food.

IMPORTANT SAFETY INFORMATION

Warnings and Precautions

Secondary Malignancies

• The risk of developing secondary malignancies is increased following treatment with Tazverik. Across clinical trials of 668 adults who received Tazverik 800 mg twice daily, myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) occurred in 0.6% of patients. One pediatric patient developed T-cell lymphoblastic lymphoma (T-LBL).

Embryo-Fetal Toxicity

• Based on findings from animal studies and its mechanism of action, Tazverik can cause fetal harm when administered to pregnant women. There are no available data on Tazverik use in pregnant women to inform the drug-associated risk. Administration of tazemetostat to pregnant rats and rabbits during organogenesis resulted in dose-dependent increases in skeletal developmental abnormalities in both species beginning at maternal exposures approximately 1.5 times the adult human exposure (area under the plasma concentration time curve [AUC0-45h]) at the 800 mg twice daily dose.
• Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with Tazverik and for 6 months after the final dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with Tazverik and for 3 months after the final dose.

Adverse Reactions

• In 62 clinical study patients with epithelioid sarcoma receiving Tazverik 800 mg twice daily: Serious adverse reactions occurring in >3% were hemorrhage, pleural effusion, skin infection, dyspnea and pain, and respiratory distress. The most common (≥20%) adverse events were pain (52%), fatigue (47%), nausea (36%), decreased appetite (26%), vomiting (24%) and constipation (21%).

Drug Interactions

• Avoid coadministration of strong or moderate CYP3A inhibitors with Tazverik. If coadministration of moderate CYP3A inhibitors cannot be avoided, reduce Tazverik dose.
• Avoid coadministration of strong or moderate CYP3A inducers with Tazverik, which may decrease the efficacy of Tazverik.
• Coadministration of Tazverik with CYP3A substrates, including hormonal contraceptives, can result in decreased concentrations and reduced efficacy of CYP3A substrates.

Lactation

• Because of the potential risk for serious adverse reactions from Tazverik in the breastfed child, advise women not to breastfeed during treatment with Tazverik and for one week after the final dose. (Article from : www.drugs.com)