Path Toward Submission for Accelerated
Approval
Epizyme, Inc. (NASDAQ:EPZM), a clinical-stage biopharmaceutical
company creating novel epigenetic therapies, today announced
positive interim data on its first-in-class EZH2 inhibitor,
tazemetostat, from the epithelioid sarcoma cohort of its ongoing
Phase 2 study in adult patients with molecularly defined solid
tumors. In addition, the Company announced that it recently
conducted a positive meeting with the U.S. Food and Drug
Administration (FDA) to discuss the registration strategy for
tazemetostat for the treatment of epithelioid sarcoma. Based on
discussions with the FDA, the Company has identified a path to
submission for accelerated approval of tazemetostat based on the
60-patient cohort from its Phase 2 study, and will target a New
Drug Application (NDA) submission in 2018.
An interim assessment of the epithelioid sarcoma cohort of
patients (n=31), as of May 1, 2017, shows that treatment with
tazemetostat resulted in a 32 percent disease control rate and a 13
percent overall response rate, with a median duration of response
of seven months and ongoing. In addition, tazemetostat continues to
demonstrate a favorable safety profile.
“Epithelioid sarcoma is a difficult cancer for sarcoma
oncologists like me to treat due to there being few available
therapeutic options, which are associated with limited benefit and
challenging side effects for patients,” said Mrinal M. Gounder,
M.D., attending physician at Memorial Sloan Kettering Cancer Center
and lead investigator in the Phase 2 clinical trial. “INI1 loss is
a defining feature of epithelioid sarcoma and the mechanism of
tazemetostat makes this a compelling agent. These data show
encouraging activity of tazemetostat as characterized by objective
responses, duration of responses and prolonged disease
stabilization, and I look forward to its continued
development." “Bringing tazemetostat to patients is our
number one priority,” said Robert Bazemore, president and chief
executive officer of Epizyme. “We stand today with a line of sight
to an expedited pathway of bringing tazemetostat to patients with
this rare and devastating form of cancer. I am very proud of the
hard work and dedication of the entire Epizyme team in advancing
tazemetostat this far, so that we may provide a new treatment
option to patients who are in desperate need of effective and
tolerable medicines.”
Phase 2 Study in Molecularly Defined Solid
Tumors Epizyme’s Phase 2 study is evaluating the efficacy
and safety of 800mg of tazemetostat orally administered twice-daily
in adult patients with certain molecularly defined solid tumors,
stratified into five different cohorts based on tumor type,
including: epithelioid sarcoma, synovial sarcoma, malignant
rhabdoid tumor, renal medullary carcinoma and other INI1-negative
tumors.
Epizyme will present interim efficacy data from the epithelioid
sarcoma and synovial sarcoma cohorts and safety data from all
cohorts at the American Society for Clinical Oncology (ASCO) Annual
Meeting. The remaining three arms of the study have not yet reached
futility assessment by the Independent Data Monitoring Committee.
Epizyme anticipates providing updates from those cohorts later in
2017.
Epithelioid Sarcoma Efficacy DataThe
epithelioid sarcoma cohort in Epizyme’s Phase 2 study represents
the largest prospective study of epithelioid sarcoma with any
approved or investigational treatment to date. Epithelioid sarcoma
is an ultra-rare and aggressive soft tissue sarcoma, characterized
by a loss of the INI1 protein. It is most commonly diagnosed in
young adults (20-40 years old) and is often fatal. There is no
established standard-of-care for treating these patients, who are
typically resistant to chemotherapy.
The cohort was initially designed to enroll 30 patients, and was
expanded to enroll an additional 30 patients in December 2016 based
on encouraging early activity. The cohort has enrolled 49
front-line and relapsed or refractory epithelioid sarcoma patients
out of a projected total of 60 patients. Interim data to be
presented are from 31 patients in the initial study group, as of
the data cutoff on May 1, 2017.
In these patients, tazemetostat treatment resulted in a 32
percent disease control rate (DCR), the primary endpoint. DCR is
comprised of confirmed objective responses by RECIST 1.1 for any
duration or disease stabilization of 32 weeks or more. Thus far,
four patients (13%) have achieved confirmed objective responses
(all partial), and the time to response ranged from two months to
six months. The median duration of response is seven months and
ongoing. Prolonged disease stabilization of 32 weeks or more has
been observed in six patients (19%), including two patients having
stable disease for more than 15 months. These Phase 2 data
complement the Company’s experience from its Phase 1 study, in
which two of three patients with epithelioid sarcoma remain on
tazemetostat with stable disease out over two years.
A median progression-free survival (PFS) of 5.7 months has been
observed, and initial assessment of overall survival for those
patients in the DCR group compared to the non-DCR group showed
distinct separation in survival curves, favoring the DCR group. The
data from this cohort are still maturing, and an initial assessment
suggests the potential for prolonged clinical benefit with
tazemetostat treatment.
These interim data will be presented at ASCO by Dr. Gounder in a
poster titled “Phase 2 multicenter study of the EZH2 inhibitor
tazemetostat in adults with INI1 negative epithelioid sarcoma
(NCT02601950)” on June 4 (Abstract No.: 11058, Poster Board No.:
381).
Tazemetostat Safety ProfileTazemetostat has
demonstrated a favorable safety profile in the Phase 2 study,
particularly when considering the adverse effects associated with
currently utilized chemotherapeutic regimens and other STS
therapies. Safety data from patients in all study cohorts (n=121)
are consistent with the overall safety profile observed in a nearly
400 patient-safety database from tazemetostat clinical trials to
date, showing favorable tolerability without significant safety
events. There were no discontinuations due to adverse events in any
of the study cohorts. The majority of treatment-emergent adverse
events (TEAEs) were grade 1 or 2, with only 12 percent of patients
experiencing grade 3 or higher treatment-related TEAEs. Reported
TEAEs regardless of attribution with an incidence of 10 percent or
greater were fatigue (34%), dyspnea and nausea (27% each), cough
(22%), decreased appetite (20%), vomiting (19%), constipation
(18%), anemia (17%), diarrhea (16%), back pain and headache (12%
each), pleural effusion (11%) and death and peripheral edema (10%
each). All deaths that occurred during the study were attributed to
the patients’ underlying disease and not to treatment with
tazemetostat.
There were no clinically relevant differences in the safety
profile for either the epithelioid sarcoma or the synovial sarcoma
cohorts compared to that of the entire study.
Synovial Sarcoma Efficacy DataThe cohort of
patients with synovial sarcoma (n=33) in the Phase 2 study
completed enrollment in November 2016. Data show tazemetostat
treatment resulted in stable disease as the best response in 10
patients (30%) with five patients (15%) meeting the primary
endpoint of disease stabilization for 16 weeks or longer. The level
of activity was determined to be insufficient to advance
tazemetostat as a monotherapy for this tumor type.
These data will be presented in a poster by Patrick Schöffski,
M.D., Department of General Medical Oncology and the Laboratory of
Experimental Oncology at the University Hospitals Leuven, KU
Leuven, Belgium, titled “Phase 2 multicenter study of the EZH2
inhibitor tazemetostat in adults with synovial sarcoma
(NCT02601950)” on June 4 (Abstract No.: 11057, Poster Board No.:
380).
Conference Call Information Epizyme will host a
conference call and audio webcast today at 8:30 a.m. Eastern Time.
To participate in the conference call, please dial (877) 844-6886
(domestic) or (970) 315-0315 (international) and refer to
conference ID 12186629. The webcast, and accompanying slides for
the call, can be accessed under "Events and Presentations" in the
Investor Relations section of the company's website at
www.epizyme.com.
About Epithelioid SarcomaEpithelioid sarcoma is
an ultra-rare soft tissue sarcoma characterized by a loss of
function of the protein INI1. Patients are most commonly diagnosed
as young adults, between 20 and 40 years of age. Median overall
survival from initial diagnosis is 30 months. Epithelioid sarcoma
becomes more aggressive after recurrence or metastases, with a
typical survival of eight to 12 months for patients with metastatic
disease. There is no approved treatment indicated specifically for
epithelioid sarcoma, and there is no established standard of
care.
About the Tazemetostat Clinical Trial
ProgramTazemetostat, a first-in-class EZH2 inhibitor, is
currently being studied in ongoing Phase 2 programs in both
follicular lymphoma and diffuse large B-cell lymphoma (DLBCL) forms
of non-Hodgkin lymphoma; certain genetically defined solid tumors,
including INI1-negative and SMARCA4-negative tumors and synovial
sarcoma; and mesothelioma; as well as in combination studies in
DLBCL. Tazemetostat has been granted Fast Track designation by the
U.S. Food and Drug Administration for both relapsed/refractory
follicular lymphoma with or without an EZH2 activating mutation and
DLBCL with EZH2 activating mutations, as well as Orphan Drug
designation for malignant rhabdoid tumors.
About Epizyme, Inc. Epizyme, Inc. is a
clinical-stage biopharmaceutical company committed to rewriting
cancer treatment through novel epigenetic medicines. Epizyme is
broadly developing its lead product candidate, tazemetostat, a
first-in-class EZH2 inhibitor, with studies underway in both solid
tumors and hematological malignancies, as a monotherapy and
combination therapy and in relapsed and front-line disease. Using
the Company’s proprietary platform, Epizyme has pioneered the
identification and development of small molecule inhibitors of
chromatin modifying proteins (CMPs), such as tazemetostat. CMPs 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 CMPs, which can allow cancer cells to
grow and proliferate. By focusing on the genetic drivers of
cancers, Epizyme's science seeks to match targeted medicines with
the specific patients that need it. For more information, visit
www.epizyme.com and connect with us on Twitter at
@EpizymeRx.
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 results from preclinical
studies or earlier clinical studies will be predictive of the
results of future studies; whether interim data from clinical
studies such as the data reported in this release will be
indicative of the final results of the study; whether results from
clinical studies will warrant meetings with regulatory authorities
or submissions for regulatory approval; whether submissions for
regulatory approval will be made when anticipated or at all and
whether these submissions will be reviewed under the accelerated
approval framework; whether the Company will receive regulatory
approvals 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:
Cheya Pope, Epizyme, Inc.
media@epizyme.com
617-229-7561
Monique Allaire, THRUST IR
monique@thrustir.com
(617) 895-9511
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