MDF Magazine Issue 64 April 2021

RESEARCH
EXON 45 SKIPPING
THERAPY FOR DMD
SHOWS SAFETY IN
SMALL TRIAL
BY MARISA WEXLER
PUBLISHED ONLINE IN MUSCULAR DYSTROPHY NEWS TODAY
JANUARY 19, 2021
different doses are reported to have
been tested, ranging from 0.1 mg/
kg to 6 mg/kg, but dosing was not
specified in the summary results
announced by Daiichi Sankyo.
Main trial goals were to evaluate the
safety and tolerability of the investigational
therapy, as well as its pharmacokinetic
profile — how the medication
moves into, through, and is
processed by the body.
A potential exon-skipping therapy
for Duchenne muscular dystrophy
(DMD) called DS-5141 showed a
good safety profile with repeat dosing
in a small clinical trial, according to a
press release.
The Phase 1/2 clinical trial
(NCT02667483) tested DS-5141
for a first time in Duchenne patients
amendable to exon 45 skipping. No
safety concerns, including clinically
significant adverse events, were
reported, and no one stopped treatment
early.
DMD is caused by mutations in
the DMD gene, which encodes the
instructions necessary to produce
dystrophin, a protein that is important
for muscle health.
DS-5141 is specifically an exon-skipping
therapy. Within a cell’s DNA, the
protein-coding parts of genes are
42
located in discreet segments called
exons. When the DNA is “read,”
these exons are strung together in
the messenger RNA, which in turn
is used to produce a protein.
DS-5141 allows the cells to skip
exon 45 when the DMD gene is read,
thereby allowing a cell to produce a
shortened ‒ but functional ‒ version
of the dystrophin protein in people
with a mutated exon 45.
The investigational therapy is being
jointly developed by Daiichi Sankyo
and the Orphan Disease Treatment
Institute in Tokyo, which specializes
in Duchenne treatments.
The trial enrolled seven boys with
DMD at two sites in Japan. DS-5141
was administered by subcutaneous
(under-the-skin) injection once
weekly for 12 weeks, followed by
once weekly for 48 weeks. Four
Another primary goal was to assess
the expression of dystrophin protein.
As announced in an earlier report,
protein expression was detected in
some, but not all, of the treated participants.
The recent release noted
“a clear increase” of dystrophin
expression in “several patients.”
A secondary goal was to assess the
production of DMD gene messenger
RNA with exon 45 skipping. This was
found in all participants.
Further analyses of trial data are
ongoing.
“Daiichi Sankyo will continue to
investigate this study’s result in detail
as part of its efforts to provide new
treatment options for patients with
DMD,” the company stated.
Article available at: https://muscular-
dystrophynews.com/2021/01/19/ds-
5141-shows-promise-in-small-dmdclinical-trial/