Fulcrum Therapeutics, Inc.
(Nasdaq: FULC), a clinical-stage biopharmaceutical company focused
on improving the lives of patients with genetically defined rare
diseases, today announced preliminary results of a Phase 1 clinical
trial of losmapimod to treat the root cause of facioscapulohumeral
dystrophy (FSHD). Losmapimod is a selective p38α/β mitogen
activated protein kinase (MAPK) inhibitor. Fulcrum exclusively
in-licensed losmapimod following Fulcrum’s discovery that the
inhibition of p38α/β reduced expression of the DUX4 gene in muscle
cells derived from patients with FSHD, a disease which is caused by
the mis-expression of DUX4 in skeletal muscle. Results were
presented today by Michelle Mellion, MD, medical director at
Fulcrum Therapeutics, in an oral presentation during the 24th
International Annual Congress of the World Muscle Society in
Copenhagen, Denmark.
“Losmapimod has previously been shown to have adequate safety
and tolerability in over 3,500 patients and healthy volunteers
across multiple indications, with no safety signals attributed to
the drug in those trials. Until now, losmapimod had not been tested
in patients with FSHD, nor was it known if it was muscle-penetrant
in humans,” said Dr. Mellion. “The preliminary results from our
Phase 1 clinical trial of losmapimod in patients with FSHD indicate
that losmapimod was generally well tolerated and achieved
dose-dependent concentrations in plasma and muscle believed to be
adequate for efficacy based on preclinical pharmacology
studies.”
The primary objective of the trial was to investigate the safety
and tolerability of losmapimod in healthy volunteers and in FSHD
patients. The secondary objective was to evaluate repeated dose
pharmacokinetics (PK) and target engagement (TE) in FSHD patients.
In the first cohort, 10 healthy volunteers were randomized to a
single oral dose of losmapimod (n=8) 7.5 mg followed by a single
oral dose of 15 mg after a wash out period or to single oral dose
placebo (n=2) in both dosing periods. In the second cohort, 15 FSHD
patients were randomized and treated with placebo (n=3) or
losmapimod 7.5 mg (n=6) or 15 mg (n=6) taken orally twice daily for
14 days.
Losmapimod was well tolerated with no serious adverse events
(SAEs) reported. Similar tolerability, safety and PK were observed
in healthy volunteers and patients with FSHD. Treatment with
losmapimod demonstrated dose-dependent PK and TE in blood. This was
consistent with previously reported data from more than 3,500
patients treated with losmapimod across multiple other indications.
FSHD patients treated with losmapimod also achieved dose-dependent
concentrations in skeletal muscle, with a muscle to plasma exposure
ratio of approximately 1:1. The losmapimod 15 mg dose taken orally
twice daily demonstrated sustained drug concentrations that in
preclinical models with human FSHD myotubes resulted in a robust
reduction of DUX4-driven gene expression. Analysis of target
engagement in muscle is ongoing. These data support the selection
of the 15 mg dose of losmapimod taken orally twice daily in the
Company’s ongoing Phase 2b placebo-controlled 24-week clinical
trial, referred to as ReDUX4, as well as its ongoing Phase 2 open
label-study of losmapimod for the treatment of patients with
FSHD.
“There are currently no approved treatment options available for
patients with FSHD. They face a lifetime of accumulating disability
that can severely impact their day-to-day function and quality of
life,” said Diego Cadavid, MD, senior vice president of clinical
development at Fulcrum Therapeutics. “We are very encouraged by
these results and are working rapidly to advance our development
program for losmapimod.”
About FSHD FSHD is characterized by progressive
skeletal muscle loss that initially causes weakness in muscles in
the face, shoulders, arms and trunk, and progresses to weakness
throughout the lower body. Skeletal muscle weakness results in
significant physical limitations, including an inability to smile
and difficulty using arms for activities, with many patients
ultimately becoming dependent upon the use of a wheelchair for
daily mobility.
FSHD is caused by mis-expression of DUX4 in skeletal muscle,
resulting in the presence of DUX4 proteins that are toxic to muscle
tissue. Normally, DUX4-driven gene expression is limited to early
embryonic development, after which time the DUX4 gene is silenced.
In people with FSHD, the DUX4 gene is turned “on” as a result of a
genetic mutation. The result is death of muscle and its replacement
by fat, leading to skeletal muscle weakness and progressive
disability. There are no approved therapies for FSHD, one of the
most common forms of muscular dystrophy, with an estimated patient
population of 16,000 to 38,000 in the United States alone.
About Losmapimod Losmapimod is a selective
p38α/β mitogen activated protein kinase (MAPK) inhibitor that was
exclusively in-licensed by Fulcrum Therapeutics following Fulcrum’s
discovery of the role of p38α/β inhibitors in the reduction of DUX4
expression and an extensive review of known compounds. Utilizing
its internal product engine, Fulcrum discovered that inhibition of
p38α/β reduced expression of the DUX4 gene in muscle cells derived
from patients with FSHD. Although losmapimod has never previously
been explored in muscular dystrophies, it has been evaluated in
more than 3,500 subjects in clinical trials across multiple other
indications, including in several Phase 2 trials and a Phase 3
trial. No safety signals were attributed to losmapimod in any of
these trials. Fulcrum is currently conducting Phase 2 trials
investigating the safety, tolerability, and efficacy of losmapimod
to treat the root cause of FSHD.
About Fulcrum Therapeutics Fulcrum Therapeutics
is a clinical-stage biopharmaceutical company focused on improving
the lives of patients with genetically defined diseases in areas of
high unmet medical need, with an initial focus on rare diseases.
Fulcrum’s proprietary product engine identifies drug targets which
can modulate gene expression to treat the known root cause of gene
mis-expression. Please visit
www.fulcrumtx.com.
Forward-Looking Statements This press release
contains “forward-looking statements” within the meaning of the
Private Securities Litigation Reform Act of 1995 that involve
substantial risks and uncertainties, including statements regarding
the development status of the Company’s product candidates and the
timing of availability of clinical trial data. All statements,
other than statements of historical facts, contained in this press
release, including statements regarding the Company’s strategy,
future operations, future financial position, prospects, plans and
objectives of management, are forward-looking statements. The words
“anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,”
“intend,” “may,” “plan,” “potential,” “predict,” “project,”
“should,” “target,” “will,” “would” and similar expressions are
intended to identify forward-looking statements, although not all
forward-looking statements contain these identifying words. Any
forward-looking statements are based on management’s current
expectations of future events and are subject to a number of risks
and uncertainties that could cause actual results to differ
materially and adversely from those set forth in, or implied by,
such forward-looking statements. These risks and uncertainties
include, but are not limited to, risks associated with Fulcrum’s
ability to obtain and maintain necessary approvals from the FDA and
other regulatory authorities; continue to advance its product
candidates in clinical trials; replicate in later clinical trials
positive results found in preclinical studies and early-stage
clinical trials of losmapimod and its other product candidates;
advance the development of its product candidates under the
timelines it anticipates in current and future clinical trials;
obtain, maintain or protect intellectual property rights related to
its product candidates; manage expenses; and raise the substantial
additional capital needed to achieve its business objectives. For a
discussion of other risks and uncertainties, and other important
factors, any of which could cause the Company’s actual results to
differ from those contained in the forward-looking statements, see
the “Risk Factors” section, as well as discussions of potential
risks, uncertainties and other important factors, in the Company’s
most recent filings with the Securities and Exchange Commission. 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: Lynn Granito Berry &
Company Public Relations lgranito@berrypr.com
212-253-8881
Investors: Christina Tartaglia Stern IR, Inc.
christina.tartaglia@sternir.com 212-362-1200
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