Updated Activity Data from Phase 1b Portion of
the Study Shows Continued Improvement in Both Objective and
Complete Response Rates
Update Includes Response Data for Sub-Group of
Patients Who Are Rituximab-Refractory and with POD24
Epizyme, Inc. (Nasdaq: EPZM), a fully integrated,
commercial-stage biopharmaceutical company developing and
delivering transformative therapies for cancer patients against
novel epigenetic targets, announced updated safety and activity
data from the Phase 1b safety run-in portion of its Phase 1b/3
confirmatory study evaluating the investigational use of
tazemetostat, a first-in-class, oral, selective inhibitor of EZH2,
in combination with rituximab + lenalidomide (R2) in patients with
relapsed/refractory follicular lymphoma (R/R FL). These patients
have been treated with at least one prior systemic therapy,
including patients who are rituximab-refractory and/or relapsed
within 24 months (POD24). These data will be presented at the 2022
American Society of Clinical Oncology (ASCO) Annual Meeting on
Saturday, June 4, 2022 during the Hematologic Malignancies Poster
Session.
The updated interim analysis of the Phase 1b study includes 44
FL patients who received treatment with tazemetostat and R2 (400 mg
[n=4], 600 mg [n=19], or 800 mg [n=21]) as of the January 22, 2022
data cutoff. The safety profile of the tazemetostat and R2
combination was consistent with the prescribing information for
both tazemetostat and R2, respectively. Additionally, there was no
clear dose response for treatment-emergent adverse events (TEAEs)
or dose modifications.
Thirty-eight of the 44 patients were evaluable for tumor
assessments as of the data cutoff, with 36 patients responding to
treatment. The activity findings showed an objective response rate
(ORR) of 95 percent (50% complete response [CR] rate and 45%
partial response [PR] rate). Two patients achieved stable disease,
and two patients had progressive disease (one from the 400-mg
cohort and one from the 600-mg cohort). Median progression-free
survival (PFS) and duration of response were not yet reached as the
study is ongoing.
This analysis also provides more in-depth characterization of
enrolled patients and their response to therapy. For patients who
are rituximab-refractory the ORR was 100 percent (n=13), with six
patients (46%) achieving a CR. For patients with POD24, 100 percent
(n=10) achieved an ORR, with four patients (40%) achieving a CR.
For patients with wild type EZH2, the ORR was 94 percent (n=30),
with 15 patients (47%) achieving a CR. For EZH2 mutation positive
patients, the ORR was 100 percent (n=5), with three patients (60%)
achieving a CR.
“Following the previous data presentation at ASH in 2021, it is
encouraging to see an increase in objective and complete response
rates for patients treated with tazemetostat in combination with
R2, especially in a difficult to treat population who are
rituximab-refractory and with POD24. We believe the improvement in
ORR and CR builds upon the findings from our preclinical data,
which showed a potential synergistic effect of tazemetostat with
lenalidomide and an additive effect with rituximab,” said Dr.
Shefali Agarwal, Senior Medical Advisor, and interim Chief Medical
and Development Officer at Epizyme. “We will continue to follow
these patients and look forward to sharing follow-up data, as
available, in addition to enrolling patients globally for the Phase
3 portion of the study.”
SYMPHONY-1 (EZH-302) is an international, multicenter,
randomized, double-blind, active-controlled, 3-stage,
biomarker-enriched, confirmatory Phase 1b/3 study, which is
designed to evaluate the safety and efficacy of tazemetostat in
combination with R2 in patients with R/R FL after at least one
prior line of therapy. The Phase 1b portion of the study is
designed to determine the recommended Phase 3 dose (RP3D),
activity, and safety of tazemetostat and R2. In addition to the
safety run-in analysis, the study also assessed the
pharmacokinetics and continues to assess clinical activity of
tazemetostat when administered in combination with R2.
The Phase 1b safety run-in component evaluated tazemetostat at
three dose levels (400 mg, 600 mg, and 800 mg orally twice daily
[BID]) in 28-day cycles with standard-dose R2 using a 3 + 3 design.
Rituximab was administered at 375 mg/m2 intravenously on days 1, 8,
15 and 22 of cycle 1, then on day 1 of cycles 2 to 5. Lenalidomide
was administered at 20 mg (creatinine clearance ≥60 mL/min) or 10
mg (if creatinine clearance <60 mL/min) orally once daily on
days 1 to 21 every 28 days for 12 cycles. In the Phase 3 component,
approximately 500 patients will be randomly assigned to receive the
RP3D of tazemetostat at 800mg BID + R2 or placebo + R2. The study
will also include a maintenance arm with tazemetostat or placebo
following the first year of treatment with tazemetostat + R2 or
placebo + R2.
Treatment with tazemetostat and R2 was generally well tolerated
and the adverse events were consistent with those contained in the
prescribing information for both tazemetostat and R2, respectively.
Grade 3/4 TEAEs were observed in 25 patients (57%); the most common
grade 3/4 TEAE was neutrophil count decrease/neutropenia (30%).
Fourteen patients (32%) reported SAEs (serious adverse events).
A table of the activity findings as of the data cutoff are
below:
Best Overall Response (BOR)
Ratea, n (%)
Tazemetostat + R2 (n =
38)b
Objective Response Rate (ORR)
36 (95)
Complete Responsec (CR)
19 (50)
Partial Response (PR)
17 (45)
Stable Disease (SD)
2 (5)
a Overall, there were 31
PET-CT-based responses and 7 CT-based responses. b Six
patients were not included in the initial efficacy assessments.
c For CR, 18 were PET-CT-based responses and 1 was a
CT-based response. CT, computed tomography; PET, positron emission
tomography; R2, lenalidomide + rituximab.
“The preliminary efficacy data and consistent safety profile we
see in this SYMPHONY-1 patient population is an exciting update for
our tazemetostat clinical program and reinforces our belief that
tazemetostat has the potential to become a backbone of therapy in
FL,” said Grant Bogle, President and Chief Executive Officer at
Epizyme. “The data shared at ASCO this weekend are the first of
several tazemetostat combination studies across both solid tumor
and hematologic malignancies that we look forward to sharing as the
data mature later this year and into next.”
In addition to the SYMPHONY-1 presentation (Abstract #7572), the
Company has one additional tazemetostat study being presented
during the ASCO Annual Meeting. The EZH-102 study (Abstract #10040)
is a Phase 1, multicenter, open-label, dose escalation (Phase 1a)
and dose expansion (Phase 1b) study evaluating tazemetostat
monotherapy in pediatric patients with R/R SMARCB1 (INI1 negative)
tumors.
About TAZVERIK® (tazemetostat)
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 two 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 confirmatory trials.
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.
View the U.S. Full Prescribing Information here: Epizyme.com
About Epizyme, Inc.
Epizyme, Inc. is a fully integrated, commercial-stage
biopharmaceutical company committed to its mission of rewriting
treatment for cancer through novel epigenetic medicines. The
Company is focused on creating medicines that are targeted at
specific causes of diseases, that are orally administered,
tolerable, easy to take and based on a deep understanding of the
patients that may benefit from them. The Company aspires to change
the standard-of-care for patients and physicians by developing
medicines with fundamentally new mechanisms of action. For more
information, visit www.epizyme.com.
TAZVERIK® is a registered trademark of Epizyme, Inc.
R2, Revlimid + Rituximab. Revlimid (lenalidomide) is a
registered trademark of Celgene Corporation, a Bristol Myers Squibb
company.
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, including, without limitation, Epizyme’s views
with respect to the safety and activity of tazemetostat based on
the updated data from the Phase 1b safety-run in portion of
Epizyme’s SYMPHONY-1 trial, the potential benefit associated with
tazemetostat, clinical development plans for tazemetostat, and
expectations around timing of additional data 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
commercial sales of TAZVERIK for epithelioid sarcoma and follicular
lymphoma in the approved indications will be successful; whether
tazemetostat will receive marketing approval for epithelioid
sarcoma or follicular lymphoma 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 trials of TAZVERIK; whether interim
results of clinical studies will be predictive of the final results
of the studies; 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 the company will receive
regulatory approvals, including accelerated approval, to conduct
trials or to market products; the impact of the COVID-19 pandemic
on the company’s business, results of operations and financial
condition; 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; and other factors discussed in the “Risk Factors”
section of the company’s most recent Form 10-K and 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.
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version on businesswire.com: https://www.businesswire.com/news/home/20220602005320/en/
Media: Erin Graves Epizyme, Inc. media@epizyme.com (617)
500-0615
Investors: Caitlin Stern cstern@realchemistry.com
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