Lugano, Switzerland — Epizyme, Inc. (NASDAQ: EPZM), a clinical stage biopharmaceutical company creating novel epigenetic therapeutics for cancer patients, today reported results from the ongoing phase 1 trial of tazemetostat (EPZ-6438), a first-in-class EZH2 inhibitor, showing meaningful clinical activity when used as an oral monotherapy in patients with advanced B-cell non-Hodgkin lymphomas (NHL) and solid tumors. In NHL, treatment with tazemetostat continues to demonstrate an encouraging profile with nine of 15 evaluable NHL patients achieving an objective response, including a partial response in the first treated patient with an EZH2 tumor mutation. The data, which include patients from the dose escalation and dose expansion cohorts of the phase 1 study, as well as a food effects sub-study, were presented today by Vincent Ribrag, M.D., Institut Gustave Roussy, at the 13th International Conference on Malignant Lymphoma.
“These results highlight the therapeutic potential of tazemetostat in NHL, with a number of patients achieving durable remissions with time on treatment at or beyond one year”
“The breadth, depth and durability of responses seen in NHL patients among multiple histologies continue to impress, as does the safety and tolerability of tazemetostat in this phase 1 study,” said Dr. Ribrag. “Among the patients in the dose escalation cohorts, we have seen a noteworthy deepening of responses over time, and in the first treated patient with an EZH2 tumor mutation, we have seen a partial response, which is very encouraging.”
As of June 8, 2015, the following clinical data were observed:
• Nine of 15 evaluable NHL patients have achieved an objective response, including two patients with an ongoing complete response (CR).
• Five of nine evaluable diffuse large B-cell lymphoma (DLBCL) patients achieved an objective response. One patient with a CR remains on study at 18 months of treatment.
• Three of five evaluable patients with follicular lymphoma achieved an objective response. One patient with a CR remains on study at 13 months, and one patient with a PR remains on study at 13 months.
• One patient with a marginal zone lymphoma achieved a partial response and continues on study at 11 months.
• All treatment responses were observed between two and 10 months on therapy.
• One of 14 patients evaluated for EZH2 status possesses a specific EZH2 tumor mutation (Y646H). This patient, who had relapsed or been refractory to six previous treatment regimens, achieved a partial response after 16 weeks of therapy and remains on study.
• The majority of adverse events were grade 1 or grade 2 within the evaluable for safety population of 45 patients with NHL and solid tumors. The most common adverse events regardless of attribution were asthenia, anorexia, anemia, dyspnea and nausea. Five grade 3 or greater treatment-related adverse events were observed including one each of: grade 3 anorexia, grade 3 hypertension, grade 3 transaminase elevation, grade 4 thrombocytopenia, and grade 4 neutropenia.
“These results highlight the therapeutic potential of tazemetostat in NHL, with a number of patients achieving durable remissions with time on treatment at or beyond one year,” said Peter Ho, M.D., Ph.D., Chief Development Officer, Epizyme. “We look forward to exploring further the clinical utility of tazemetostat in NHL in a robust phase 2 development program.”
The NHL patients enrolled on study were heavily pre-treated, with 85 percent of patients having received three or more prior therapies and 37 percent of patients having received more than five or more prior therapies. Thirty-seven percent of patients were refractory to their last prior regimen and 26 percent of patients had received a prior autologous hematopoietic stem cell transplant.
Drug pharmacokinetics showed rapid absorption with a mean terminal half-life of three to five hours. Cmax and AUC1-12hr were dose proportional at steady-state throughout the dosing range. Steady-state Ctrough levels were reached by day 15.
The company plans to report a further update from the phase 1 trial by the end of 2015.
This open-label, multi-center, phase 1 study is investigating tazemetostat as monotherapy in patients with relapsed or refractory B-cell non-Hodgkin lymphomas or advanced solid tumors. The study objectives include identification of the recommended phase 2 dose or maximum tolerated dose, safety, tolerability, pharmacokinetics and preliminary evaluation of anti-tumor activity. Five cohorts were studied in the dose escalation phase: 100 mg, 200 mg, 400 mg, 800 mg and 1600 mg; and two cohorts, 800 mg and 1600 mg, were evaluated in the dose expansion phase. All doses were given twice daily.
Expanded Tazemetostat Phase 2 Plans
Epizyme is now enrolling patients in an international five-arm, multi-center, phase 2 study during the second quarter of 2015 that will assess the safety and efficacy of tazemetostat in patients with relapsed or refractory NHL, stratified by cell of origin and EZH2 mutation status. A second planned phase 2 trial of tazemetostat in adult patients with INI1-deficient solid tumors is expected to begin later in 2015. Patients in both studies will be treated with the recommended phase 2 dose of 800 mg twice daily. A phase 1 study in pediatric patients with INI1-deficient solid tumors is also expected to start later in 2015.
In addition to these previously announced studies, the company plans to initiate additional trials of tazemetostat, including:
• A combination study of tazemetostat with R-CHOP in patients with DLBCL. R-CHOP, which represents current first-line treatment for patients with DLBCL, is comprised of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone.
• A combination study of tazemetostat with a B-cell signaling agent or other emerging targeted therapies for B-cell lymphomas.
“Conducting combination studies in B-cell lymphoma will further elucidate the clinical potential of tazemetostat,” said Dr. Ho. “Scientists here at Epizyme have demonstrated pre-clinical synergy with both current standard-of-care therapeutics and emerging investigational agents, and we believe that tazemetostat has a safety and tolerability profile that will lend itself well to combination regimens.”
About EZH2 in Cancer
EZH2 is a histone methyltransferase (HMT) that is increasingly understood to play a potentially oncogenic role in a number of cancers. These include non-Hodgkin lymphomas, INI1-deficient cancers such as malignant rhabdoid tumors, epithelioid sarcomas and synovial sarcoma; and a range of other solid tumors.
Epizyme is developing tazemetostat for the treatment of non-Hodgkin lymphoma patients and patients with INI1-deficient solid tumors. Tazemetostat is a first-in-class small molecule inhibitor of EZH2 created by Epizyme using its proprietary product platform. In many human cancers, aberrant EZH2 enzyme activity results in misregulation of genes that control cell proliferation resulting in the rapid and unconstrained growth of tumor cells. Tazemetostat is the WHO International Non-Proprietary Name (INN) for EPZ-6438.
Tazemetostat is the second HMT inhibitor to enter human clinical development (following Epizyme’s DOT1L inhibitor, pinometostat, also known as EPZ-5676).
About Epizyme, Inc.
Epizyme, Inc. is a clinical stage biopharmaceutical company creating novel epigenetic therapeutics for cancer patients. Epizyme has built a proprietary product platform that the Company uses to create small molecule inhibitors of a 96-member class of enzymes known as histone methyltransferases, or HMTs. HMTs are part of the system of gene regulation, referred to as epigenetics, that controls gene expression. Genetic alterations can result in changes to the activity of HMTs, making them oncogenic (cancer-causing). By focusing on the genetic drivers of cancers, Epizyme’s targeted science seeks to match the right medicines with the right patients.
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 or expansion of ongoing clinical studies; availability and timing of data from ongoing clinical studies; whether interim results from a clinical trial such as the results referred to in this release will be predictive of the final results of the trial or the results of future trials; expectations for regulatory approvals to conduct trials or to market products; development progress of the Company’s companion diagnostics, availability of funding sufficient for 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 or companion diagnostics; and other factors discussed in the “Risk Factors” section of the company’s Form 10-Q filed with the SEC on April 28, 2015, and in our 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. 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. These forward-looking statements should not be relied upon as representing the Company’s views as of any date subsequent to the date hereof.