Metacrine Reports Interim Results for MET642 Phase 2a Trial in Patients with NASH and Announces a Strategic Re-Prioritization of Its Clinical Development Programs
2021年10月22日 - 5:01AM
Metacrine, Inc. (NASDAQ:MTCR), a clinical-stage biopharmaceutical
company pioneering differentiated therapies for patients with liver
and gastrointestinal diseases, today reported interim results from
a Phase 2a clinical trial evaluating the efficacy and safety of
MET642, a farnesoid X receptor (FXR) agonist, in approximately 60
non-alcoholic steatohepatitis (NASH) patients after 16 weeks of
treatment. The Company also announced it is prioritizing its
clinical development effort and resources to advance MET642 into a
Phase 2 trial in inflammatory bowel disease (IBD) in the first half
of 2022.
The Phase 2a trial (NCT04773964) is a 16-week, randomized,
placebo-controlled, multi-center trial evaluating the safety,
tolerability and pharmacological activity of MET642, as measured by
reductions in liver fat content with magnetic resonance
imaging-derived proton density fat fraction (MRI-PDFF), changes in
liver enzymes, low-density lipoprotein cholesterol (LDL-C) levels
and incidence of pruritus, at 3 mg and 6 mg dose levels.
MET642 lowered liver fat content, with mean relative reductions
of 26.9±27.8 percent in the 3 mg cohort and 9.3±55.8 percent in the
6 mg cohort, compared with 7.5±21.0 percent in the placebo arm.
Post-hoc comparative assessment of relative liver fat reduction in
the interim cohort found the decrease with 3 mg to be statistically
significant compared to placebo (p=0.006). MET642 achieved greater
than 30 percent liver fat reduction in 47 percent of patients
(8/17) in the 3 mg cohort and 35 percent (6/17) in the 6 mg cohort,
compared with 12 percent (2/17) in the placebo arm.
MET642 was generally well-tolerated, with no treatment-related
serious adverse events (AEs). All treatment-related AEs were
mild-moderate with no apparent dose relationship. Mild-moderate
pruritus was reported in one patient in the 3 mg cohort and one
patient in the 6 mg cohort. No pruritus-related treatment
discontinuations occurred. MET642 treatment resulted in on-target
mean increases in LDL-C of 5 percent with the 3 mg dose and 19
percent with the 6 mg dose, versus a decline of 10 percent with
placebo, from baseline to week 16.
Mean Change (Baseline to Week 16) |
Placebo (N=20) |
3 mg (N=21) |
6 mg (N=20) |
Liver Fat Reduction (MRI-PDFF) % ±SD |
-7.5% ± 21.0% |
-26.9% ± 27.8% |
-9.3% ± 55.8% |
Median Liver Fat Reduction (MRI-PDFF) % |
-1.5% |
-28.6% |
-26.9% |
% of patients with >30% Liver Fat Reduction (MRI-PDFF) |
11.8% |
47.1% |
35.3% |
LDL-C % |
-10.5% |
4.5% |
19.4% |
Overall Pruritus Rate % |
10.0% |
5.0% |
5.0% |
Pruritus-Related Treatment Discontinuation % |
0.0% |
0.0% |
0.0% |
In addition, the Company is conducting an independent review of
preliminary findings from a recently completed nine-month animal
toxicology study for MET642, which may result in the need for an
additional long-term animal toxicology study to support Phase 3
clinical trials in IBD. Metacrine expects the independent review to
be completed before the end of 2021.
“We are encouraged by the MET642 interim clinical trial results,
as this product candidate demonstrated meaningful liver fat
reduction at 3 mg and a potentially class-leading tolerability
profile for the treatment of NASH at both 3 mg and 6 mg,” said
Preston Klassen, M.D., MHS, CEO, Metacrine. “In this small interim
analysis, the 6 mg cohort displayed a non-normal distribution in
liver fat changes, as evidenced by differences between the mean and
median results. Further clarification of the impact on liver fat at
the 6 mg dose will require examination of the complete trial data
set, which is anticipated in the first half of 2022. NASH is a
complex and chronic disease that we believe will likely require
combination regimes to most effectively treat patients. MET642 can
potentially serve as an important part of these novel combination
approaches.”
Klassen continued, “After a rigorous assessment of our NASH and
IBD programs, including the significant capital and resources
required to progress these large clinical development programs, we
have made the decision to focus Metacrine’s clinical development
effort and financial resources on moving MET642 into a Phase 2
trial in IBD in the first half of 2022 and to halt future
development of the FXR program in NASH. This decision was
influenced in part by a potential delay in confirming appropriate
safety margins in our long-term toxicology work that would impact
the timing of future NASH studies, but is unlikely to impact
timelines for the IBD clinical program.”
Klassen concluded, “The rationale for FXR-based therapies in IBD
holds great promise and is anchored on the potential to address
multiple aspects of IBD pathogenesis without the immunosuppression
inherent to other advanced-line therapies. FXR is highly expressed
by intestinal epithelial cells and plays a key role in healthy
intestinal function by maintaining the epithelial barrier, reducing
bacterial translocation into the intestinal wall and regulating the
innate immune response. Metacrine’s preclinical studies supporting
a role for FXR agonism in IBD are corroborated by significant
evidence from the scientific literature. FXR therapy could
potentially change the IBD treatment paradigm by bringing an oral,
once-daily, well-tolerated and non-immunosuppressive medicine to
patients. New approaches are clearly needed that expand therapeutic
options for people living with IBD and we are excited to advance
MET642 into clinical investigation in this important disease.”
About Metacrine
Metacrine, Inc. is a clinical-stage biopharmaceutical company
building a pipeline of differentiated therapies to treat liver and
gastrointestinal diseases. Metacrine has developed a proprietary
farnesoid X receptor (FXR) platform utilizing a unique chemical
scaffold, which has demonstrated an improved therapeutic profile in
clinical trials. To learn more, visit www.metacrine.com.
Forward-Looking Statements This press release
contains forward-looking statements within the meaning of the
Private Securities Litigation Reform Act of 1995. Statements in
this press release that are not purely historical are
forward-looking statements. Such forward-looking statements
include, among other things, Metacrine’s clinical development of
MET642, the uncertainties inherent in clinical testing; future
plans or expectations for MET642, as well as the dosing, safety and
tolerability of MET642, plans for initiating future clinical trials
and studies; statements regarding the therapeutic potential of
MET642; the timing, outcome and potential impact of the independent
review of the animal toxicology study of MET642; plans for
advancing the clinical development of Metacrine’s FXR and IBD
programs; the potential leading nature of MET642 and Metacrine’s
FXR program; the potential for combination therapies to be used for
NASH, the potential for its FXR product candidates to be used in
combination therapies; and the potential for its FXR product
candidates to be long-term therapies for NASH and IBD. Words such
as “could,” “may,” “will,” “expect,” “plan,” “aim,” “projected,”
“likely,” ”anticipate,” “estimate,” “intend,” “potential,”
“prepare,” “perceived,” “believes” and similar expressions (as well
as other words or expressions referencing future events, conditions
or circumstances) are intended to identify forward-looking
statements. These forward-looking statements are based on
Metacrine’s expectations and assumptions that may never materialize
or prove to be incorrect. Each of these forward-looking statements
involves risks and uncertainties. Actual results may differ
materially from those projected in any forward-looking statements
due to numerous risks and uncertainties, including but not limited
to: positive results from a clinical study may not necessarily be
predictive of the results of future or ongoing clinical studies,
risks and uncertainties regarding regulatory approvals for MET642;
potential delays in initiating, enrolling or completing any
clinical trials; potential adverse side effects or other safety
risks associated with Metacrine’s product candidates; competition
from third parties that are developing products for similar uses;
and Metacrine’s ability to obtain, maintain and protect its
intellectual property. Information regarding the foregoing and
additional risks may be found in the section entitled “Risk
Factors” in Metacrine’s Quarterly Report on Form 10-Q filed with
the Securities and Exchange Commission (the “SEC”) on August 12,
2021, and in Metacrine’s other filings with the SEC. All
forward-looking statements contained in this press release speak
only as of the date on which they were made. Except as required by
law, Metacrine assumes no obligation to update any forward-looking
statements contained herein to reflect any change in expectations,
even as new information becomes available.
Investor & Media ContactSteve
Kunszabo Metacrine,
Inc.+1 (858) 369-7892 skunszabo@metacrine.com
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