Epizyme Announces U.S. FDA Accelerated Approval of TAZVERIK™ (tazemetostat) for Relapsed/Refractory Follicular Lymphoma

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• Adult patients with relapsed or refractory FL whose tumors are positive for an EZH2 mutation as detected by an FDA-approved test and who have received at least two prior systemic therapies.
• Adult patients with relapsed or refractory FL who have no satisfactory alternative treatment options.

These indications were approved under accelerated approval with a priority review, based on overall response rate and duration of response in the company’s Phase 2 clinical trial cohorts of FL patients with EZH2 mutations and wild-type EZH2. TAZVERIK received initial accelerated approval by FDA on January 23, 2020 for the treatment of adult and pediatric patients aged 16 years and older with metastatic or locally advanced epithelioid sarcoma not eligible for complete resection.

“We are very pleased to be able to offer TAZVERIK as a treatment option for relapsed or refractory FL patients, which is the culmination of many years of work by our team,” said Dr. Shefali Agarwal, chief medical officer of Epizyme. “In our view, there remains no clear standard of care in the relapsed and/or refractory FL population as not all patients benefit from today’s available therapies. Based on this label, physicians will have the ability to use their clinical discretion to prescribe TAZVERIK for their relapsed or refractory patients regardless of EZH2 mutational status and without regard to a specific line of treatment where other options are not satisfactory. We are grateful to the many patients, physicians and medical teams who helped bring us to this important achievement.”

“Follicular lymphoma remains an incurable disease, and even with the availability of new drugs in recent years, there have remained important unmet needs in the treatment of follicular lymphoma,” said John P. Leonard, M.D., the Richard T. Silver Distinguished Professor of Hematology and Medical Oncology at Weill Cornell Medicine, an oncologist at NewYork-Presbyterian/Weill Cornell Medical Center, and an investigator in the Phase 1b/3 confirmatory trial for TAZVERIK for FL. “The durable responses observed with this drug are notable in the context of the safety profile and route of oral, at-home administration, and will offer an important new option for physicians as we care for patients with relapsed/refractory follicular lymphoma.”

Continued approval for these indications may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). Epizyme is conducting a single global, randomized, adaptive confirmatory trial to evaluate the combination of TAZVERIK with “R²” (Revlimid^® plus rituximab), an approved chemo-free treatment regimen, for FL patients in the second-line or later treatment setting. The trial is expected to enroll approximately 500 FL patients, stratified based on their EZH2 mutation status, and the safety run-in portion is underway. In addition, Epizyme will conduct post-marketing commitments, including expanding its Phase 2 clinical trial cohort of FL patients with wild-type EZH2 who have been treated with at least one prior systemic treatment to enroll additional patients, in order to support a potential label expansion in the second-line relapsed and refractory setting in the future.

“Despite witnessing numerous advancements for people with blood cancer over the past several years, many patients diagnosed with follicular lymphoma must still contend with relapse or recurrence as well the challenge of adverse events. For these reasons, and given that most patients manage their disease over a long time period, expanded treatment options can transform the patient experience and offer new hope,” said Lymphoma Research Foundation chief executive officer, Meghan Gutierrez.

“This accelerated approval is an incredible achievement for Epizyme, marking the second approval for TAZVERIK, the first FDA approved EZH2 inhibitor, in less than six months,” said Robert Bazemore, president and chief executive officer of Epizyme. “Building off our successful commercial launch of TAZVERIK for epithelioid sarcoma earlier this year, we have seamlessly expanded our organization and are fully prepared to begin engaging physicians and to launch in FL. The ability to reach patients who need a new treatment like TAZVERIK is at the core of everything we do, and we are incredibly proud of this milestone and the ability to impact patients’ lives.”

Phase 2 Follicular Lymphoma Cohort Efficacy and Safety Data

The efficacy of TAZVERIK was evaluated in an open-label, single-arm, multi-center Phase 2 clinical trial (Study E7438-G000-101, NCT01897571) in patients with histologically confirmed FL whose disease had progressed following at least two prior systemic treatment regimens. Patients were enrolled into two cohorts: one cohort enrolled 45 patients with EZH2 activating mutations and a second cohort enrolled 54 patients with wild-type EZH2. All patients were treated with 800 mg of tazemetostat, administered orally twice a day. The major efficacy outcome measures were overall response rate (ORR) and duration of response (DOR) according to the International Working Group Non-Hodgkin Lymphoma (IWG-NHL) criteria (Cheson 2007) as assessed by Independent Review Committee. Median duration of follow-up was 22 months for patients with EZH2 activating mutations and 36 months for patients with wild-type EZH2.

Among the 45 FL patients with an EZH2 activating mutation who received TAZVERIK, the median age was 62 years (range 38 to 80); 42% were male; 42% had early progression following front-line therapy (POD24); and all had an ECOG performance status (PS) of 0 or 1. The median number of lines of prior systemic therapy was 2.0 (range 1 to 11); 49% were refractory to rituximab and 49% were refractory to their last therapy. In the 42 patients treated with at least 2 prior systemic therapies, the ORR (95% confidence interval) was 69% (53%, 82%), with 12% of patients achieving a complete response and 57% achieving a partial response. The median DOR was 10.9 months and ongoing.

Among the 54 FL patients with wild-type EZH2 who received TAZVERIK, the median age was 61 years (range 36 to 87); 63% were male; 59% had POD24; and 91% had an ECOG PS of 0 or 1. The median number of lines of prior systemic therapy was 3.0 (range 1 to 8); 59% were refractory to rituximab and 41% were refractory to their last therapy. In the 53 patients treated with at least 2 prior systemic therapies, the ORR (95% confidence interval) was 34% (22%, 48%), with 4% of patients achieving a complete response and 30% achieving a partial response. The median DOR was 13.0 months.

Serious adverse reactions, irrespective of attribution, occurred in 30% of patients receiving TAZVERIK. Serious adverse reactions in ≥2% of patients who received TAZVERIK were general physical health deterioration, abdominal pain, pneumonia, sepsis, and anemia. The most common (≥20%) adverse reactions are fatigue, upper respiratory tract infection, musculoskeletal pain, nausea and abdominal pain.

Eight patients (8%) discontinued due to adverse reaction during the trial. There were no reported deaths on study, and no black box warnings or contraindications.

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.
• Adult patients with relapsed or refractory follicular lymphoma whose tumors are positive for an EZH2 mutation as detected by an FDA-approved test and who have received at least 2 prior systemic therapies.
• Adult patients with relapsed or refractory follicular lymphoma who have no satisfactory alternative treatment options.

These indications are approved under accelerated approval based on overall response rate and duration of response. Continued approval for these indications may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

The most common (≥20%) adverse reactions in patients with epithelioid sarcoma are pain, fatigue, nausea, decreased appetite, vomiting and constipation. The most common (≥20%) adverse reactions in patients with follicular lymphoma are fatigue, upper respiratory tract infection, musculoskeletal pain, nausea and abdominal pain.

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 729 adults who received TAZVERIK 800 mg twice daily, myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) occurred in 0.7% of patients. One pediatric patient developed T-cell lymphoblastic lymphoma (T LBL). Monitor patients long-term for the development of secondary malignancies.

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

Epithelioid Sarcoma

• In 62 clinical study patients with epithelioid sarcoma receiving TAZVERIK 800 mg twice daily: Serious adverse reactions occurred in 37% of patients who received TAZVERIK. Serious adverse reactions occurring in ≥3% were hemorrhage, pleural effusion, skin infection, dyspnea, pain, and respiratory distress. The most common (≥20%) adverse reactions were pain (52%), fatigue (47%), nausea (36%), decreased appetite (26%), vomiting (24%), and constipation (21%).

Relapsed or Refractory Follicular Lymphoma

• In 99 clinical study patients with relapsed or refractory follicular lymphoma receiving TAZVERIK 800 mg twice daily: Serious adverse reactions occurred in 30% of patients who received TAZVERIK. Serious adverse reactions occurring in ≥2% were general physical health deterioration, abdominal pain, pneumonia, sepsis, and anemia. The most common (≥20%) adverse reactions were fatigue (36%), upper respiratory tract infection (30%), musculoskeletal pain (22%), nausea (24%), and abdominal pain (20%).

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 moderate and strong 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.

Epizyme notes that Dr. Leonard is a paid consultant for Epizyme.

Investor Conference Call

Epizyme will host an investor conference call and webcast today at 2:30 p.m. ET. To participate in the call, please dial (877) 844-6886 (domestic) or (970) 315-0315 (international) and refer to conference ID 2277785. A live webcast will be available in the investor section of the company’s website at www.epizyme.com. The webcast will be archived on the website for 60 days.

About Epizyme, Inc.

Epizyme, Inc. is a fully integrated, commercial-stage biopharmaceutical company committed to its mission of rewriting treatment for cancer and other serious diseases through novel epigenetic medicines. In addition to an active research and discovery pipeline, Epizyme has one U.S. FDA approved product, TAZVERIK™ (tazemetostat), for the treatment of adults and pediatric patients aged 16 years and older with metastatic or locally advanced epithelioid sarcoma (ES) who are not eligible for complete resection; adult patients with relapsed or refractory follicular lymphoma whose tumors are positive for an EZH2 mutation as detected by an FDA-approved test and who have received at least 2 prior systemic therapies; and adult patients with relapsed or refractory follicular lymphoma who have no satisfactory alternative treatment options. These indications are approved under accelerated approval based on overall response rate and duration of response. Continued approval for these indications may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). The company is also exploring the treatment potential of tazemetostat in investigational clinical trials in other solid tumors and hematological malignancies, as a monotherapy and combination therapy in both relapsed and front-line disease settings. By focusing on the genetic drivers of disease, Epizyme seeks to match medicines with the patients who need them. For more information, visit www.epizyme.com.

Cautionary Note on Forward-Looking Statements

Any statements in this press release about future expectations, plans and prospects for Epizyme, Inc. and other statements containing the words “anticipate,” “believe,” “estimate,” “expect,” “intend,” “may,” “plan,” “predict,” “project,” “target,” “potential,” “will,” “would,” “could,” “should,” “continue,” and similar expressions, constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including: whether tazemetostat will receive marketing approval for epithelioid sarcoma in other jurisdictions, full approval in the United States or approval in any other indication; whether results from preclinical studies or earlier clinical studies will be predictive of the results of future trials, such as the ongoing confirmatory trial; whether results from clinical studies will warrant meetings with regulatory authorities, submissions for regulatory approval or review by governmental authorities under the accelerated approval process; expectations for regulatory approvals, including accelerated approval, to conduct trials or to market products; whether the company’s cash resources will be sufficient to fund the company’s foreseeable and unforeseeable operating expenses and capital expenditure requirements; other matters that could affect the availability or commercial success of tazemetostat or the company’s therapeutic candidates; and other factors discussed in the “Risk Factors” section of the company’s most recent Form 10-Q filed with the SEC and in the company’s other filings from time to time with the SEC. In addition, the forward-looking statements included in this press release represent the company’s views as of the date hereof and should not be relied upon as representing the company’s views as of any date subsequent to the date hereof. The company anticipates that subsequent events and developments will cause the company’s views to change. However, while the company may elect to update these forward-looking statements at some point in the future, the company specifically disclaims any obligation to do so.

TAZVERIK™ is a trademark of Epizyme, Inc.

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