NDA Submission for Accelerated Approval of Tazemetostat for Patients with Relapsed or Refractory Follicular Lymphoma on Track for December 2019
Epizyme, Inc. (Nasdaq: EPZM), a late-stage biopharmaceutical company developing novel epigenetic therapies, today reported positive, mature data at the 2019 American Society of Hematology (ASH) Annual Meeting from its ongoing Phase 2 trial of tazemetostat, an oral EZH2 inhibitor, as a monotherapy for patients with follicular lymphoma (FL), both with or without EZH2 activating mutations, who have received at least two prior lines of systemic therapy.
The data show that treatment with tazemetostat demonstrated meaningful clinical activity as assessed by both investigators and an Independent Review Committee (IRC), and was generally well tolerated in both FL patients with EZH2 activating mutations (n=45) and FL patients with wild-type EZH2 (n=54). The IRC assessment was conducted for inclusion in Epizyme’s planned NDA submission to the U.S. Food and Drug Administration (FDA) in December 2019.
As assessed by the IRC, as of an August 9, 2019 data cutoff date, tazemetostat treatment resulted in:
§  Objective response rate (ORR) of 69% for patients with an EZH2 mutation and 35% for patients with wild-type EZH2
§  Median duration of response of 11 months for patients with an EZH2 mutation and 13 months for patients with wild-type EZH2
§  Median progression-free survival of 14 months for patients with an EZH2 mutation and 11 months for patients with wild-type EZH2
§  Overall survival has not yet been reached for either FL patient population
“Follicular lymphoma remains an incurable disease today, and it’s essential that patients be able to receive treatment for an extended period of time,†said Dr. Shefali Agarwal, chief medical officer of Epizyme. “We believe the clinically meaningful benefit of tazemetostat seen across both FL patient populations in this trial, along with its continued tolerability, are impressive findings. We are particularly pleased with the robust response rates, extended durability and consistency of data as assessed by investigators and independent reviewers. These data support tazemetostat’s potential to make a difference for FL patients, and we look forward to submitting our NDA for both patient populations later this month.â€
Follicular Lymphoma Phase 2 Cohort Design
Follicular lymphoma patients who had been previously treated with two or more systemic therapies were enrolled into two cohorts in the Phase 2 study. One cohort enrolled 45 patients with EZH2 activating mutations and a second enrolled 54 patients with wild-type EZH2. All patients were treated with 800 mg of tazemetostat, administered orally twice a day. The primary endpoint of the study is ORR, as assessed by the investigator, and defined as a complete response or partial response according to 2007 Cheson criteria. Secondary endpoints include duration of response, progression free survival, overall survival and safety.
Detailed Efficacy Results
The updated data were reported in an oral presentation entitled “Phase 2 Multicenter Study of Tazemetostat, an EZH2 Inhibitor, in Patients with Relapsed or Refractory Follicular Lymphoma†by Franck Morschhauser, M.D., Ph.D., Centre Hospitalier Régional Universitaire de Lille, France, an investigator in the Phase 2 trial. Efficacy data as assessed by both investigators and the IRC are summarized below:
|
Best Response |
FL with EZH2 MT |
FL with EZH2 WT |
||
|
 |
n=45 |
n=54 |
||
|
 |
Investigator |
IRC |
Investigator1 |
IRC2 |
|
Objective Response Rate, % (n) |
78% (35) |
69% (31) |
33% (18) (21.1-47.5) |
35% (19) (22.7-49.4) |
|
Complete Response, % (n) |
9% (4) |
13% (6) |
6% (3) |
4% (2) |
|
Partial Response, % (n) |
69% (31) |
56% (25) |
28% (15) |
31% (17) |
|
Stable Disease, % (n) |
22% (10) |
29% (13) |
30% (16) |
33% (18) |
|
Progressive Disease, % (n) |
0%, (0) |
2% (1)3 |
30% (16) |
22% (12) |
|
Patients Ongoing, % (n) |
25.7% (9) |
29% (13) |
5.6% (1) |
0% (0) |
|
Duration of Response, |
8.3 months (5.5-13.8) |
10.9 months (7.2-not reached) |
14.7 months (7.6-not reached) |
13 months (5.6-not reached) |
|
Progression-Free Survival, |
13.8 months (8.4-16.4) |
13.8 months (10.7-22.0) |
5.6 months (3.3-11.1) |
11.1 months (3.7-14.6) |
|
1Â Four patients not evaluable, or have missing or unknown data |
Safety Results
Favorable safety and tolerability have been observed with tazemetostat in these ongoing Phase 2 study cohorts. The most frequently reported treatment-related treatment-emergent adverse events (TEAEs) of Grade 3 or higher included thrombocytopenia (3%), anemia (2%), asthenia (1%) and fatigue (1%). TEAEs led to only 8% of patients discontinuing tazemetostat treatment and 9% of patients requiring a dose reduction. There were no treatment-related deaths while on study.
“We are thrilled to present these mature clinical data, which support our planned NDA submission for tazemetostat as a treatment for patients with follicular lymphoma,†said Robert Bazemore, president and chief executive officer of Epizyme. “We have made tremendous progress in advancing our tazemetostat program, with multiple clinical and regulatory achievements this year. Our NDA for epithelioid sarcoma is under review, and we have finalized our commercial readiness plans in anticipation of an early 2020 launch. We have multiple clinical trials ongoing for tazemetostat in additional indications and combinations, and we are well underway with preparations to submit the FL NDA later this month. If approved, tazemetostat would be a first-in-class EZH2 inhibitor for patients with FL, representing an important new treatment with demonstrated efficacy, durability and safety.â€
About the Tazemetostat Clinical Trial Program
Tazemetostat, an oral, potent, first-in-class EZH2 inhibitor, is currently being studied as a monotherapy in ongoing clinical programs in patients with certain molecularly defined solid tumors, including epithelioid sarcoma and other INI1-negative tumors, and in patients with follicular lymphoma, both with and without EZH2 activating mutations. Multiple clinical studies are underway through collaborations assessing tazemetostat as a combination treatment for patients with diffuse large B-cell lymphoma. Epizyme is also conducting additional clinical trials designed to evaluate the potential benefit of tazemetostat in earlier lines of therapy for follicular lymphoma, as well as new combinations and cancer indications.
About Epizyme, Inc.
Epizyme, Inc. is a late-stage biopharmaceutical company committed to rewriting treatment for cancer and other serious diseases through novel epigenetic medicines. Epizyme is broadly developing its lead product candidate, tazemetostat, an oral, first-in-class EZH2 inhibitor, with studies underway in both solid tumors and hematological malignancies, as a monotherapy and combination therapy in relapsed and front-line disease. The company is also exploring additional molecules in its novel G9a inhibitor program. By focusing on the genetic drivers of disease, Epizyme’s science seeks to match targeted 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: uncertainties inherent in the initiation of future clinical studies and in the availability and timing of data from ongoing clinical studies; whether interim results from a clinical trial will be predictive of the final results of the trial; whether results from preclinical studies or earlier clinical studies will be predictive of the results of future trials; 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; whether Fast Track Designation and Orphan Drug Designations will provide the benefits for which tazemetostat is eligible; 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 potential of 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.
Contacts
Media:
Erin Graves, (617) 500-0615
Epizyme, Inc.
media@epizyme.com
Investors:
Alicia Davis, (910) 620-3302
THRUST Strategic Communications
alicia@thrustsc.com