PKD Life - Spring 2022 - 23

eventually leading to CKD
and, in many instances, kidney
failure.
" The initial trigger may be
diff erent, but the ongoing
infl ammation and fi brosis
leading to structural kidney
damage are similar
across other
kidney diseases, "
says Seemi
Khan, M.D., chief
medical offi cer
at Reata Pharmaceuticals,
which
is bringing
bardoxolone
to market.
The drug is
signifi cantly aff ect quality of
life by helping people with
ADPKD avoid dialysis and
kidney transplant.
Reata is also seeking
Bardoxol o
may prote ct
kidne ys
fr om furthe r
damage and
preserve the ir
ab il it y to fi lte r
was  fr om
t bl oo d.
currently being tested in the
FALCON trial, in which more
than 500 people ages 18 to
70 with ADPKD and CKD will
receive either bardoxolone
or a placebo (a sugar pill) for
100 weeks, then be followed
for a period of several weeks
with no treatment. After
completing the FALCON
study, these patients will be
enrolled in an open-label,
long-term extension study,
which means everyone will
receive the study drug and
have routine monitoring
by the study team, until
the Food and Drug
Administration (FDA) makes
its approval decision.
The drug is not a onetime
cure, says Dr. Khan,
and it will be required for
the rest of a person's life to
maintain the benefi ts. But
if it can delay the progression
of CKD and the time to
dialysis, she says, it could
approval for bardoxolone in
patients with the rare genetic
condition Alport
syndrome, which
leads to CKD.
The drug was
tested in a clinical
trial in which
157 participants
received bardoxolone
or a
placebo for two
years. Those who
received bardoxolone
showed a signifi cant
improvement and preservation
in their kidney function,
which continued up to four
weeks after their fi nal dose.
The most common side
eff ects were muscle spasms
and some increases in liver
enzymes, neither of which
was serious, Dr. Khan says.
While the FDA is expected
to decide on bardoxolone
approval for Alport syndrome
in February (after
this issue goes to press), in
December an FDA advisory
committee voted against
recommending the drug
for approval, citing a combination
of trial fl aws and
safety concerns.
Dr. Khan says the FALCON
study is continuing without
interruption, but due to the
advisory committee's decision,
Reata is talking to the
FDA about possible modifi -
cations to the FALCON study.
LIXIVAPTAN
You can think of the investigational
drug lixivaptan as
a cousin of tolvaptan. Both
are in the same family of
medicines called vasopressin
V2 receptor antagonists.
Both work to block processes
in the kidney that
can reduce kidney function.
But each has its own chemical
structure.
One of the challenges
with tolvaptan is that it can
cause liver damage. It usually
improves once the drug
is stopped but can still cause
serious problems. So, people
must have blood tests before
they start on the drug and
again two and four weeks
after. They then require
monthly liver blood tests for
18 months and then every
three months thereafter.
But because lixivaptan
has a diff erent chemical
structure than tolvaptan,
the hypothesis
is that it won't
have the same
liver toxicity.
More clinical
data is being
collected in the
current and
planned phase
3 clinical trials
to test this
hypothesis, says
Neil Shusterman,
M.D., chief
medical offi cer of Palladio
Biosciences, which is developing
the drug.
Palladio launched a
phase 3 clinical study for
lixivaptan called ACTION
at the end of 2021 to evaluate
the drug's safety and
eff ectiveness in people with
ADPKD. The goal is to enroll
1,200 people, two-thirds of
whom will receive lixivaptan,
and the rest a placebo.
After 52 weeks, everyone
will stop taking the medication
or placebo for four
weeks, then all will receive
lixivaptan for another year.
Palladio is also testing lixBecause
ivaptan
in the ALERT study,
a phase 3 clinical trial in
which up to 50 people with
ADPKD who had to stop
taking tolvaptan because of
abnormal liver enzyme tests
will receive lixivaptan for up
to 58 weeks. The rationale
for this approach is based
on a single patient who had
to stop taking tolvaptan
because of liver issues, but
who received lixivaptan for
14 months afterward with
no abnormal
liver chemistry
lixiva ptan
has a diff erent
ch emic
st ructure than
to lva ptan, t
hypothe sis is
that  won't
have t same
liver to xicit y.
test results.
" All advancements
in science
and drug development
depend
on people volunteering
for
clinical trials, " Dr.
Shusterman says.
" We never would
have had the
many modern
pharmaceutical products in
current use if people hadn't
volunteered for the studies
needed to test those drugs,
for which we are grateful. "
*
TO LEARN MORE ABOUT PKD RESEARCH, VISIT PKDCURE.ORG/RESEARCH
23
http://www.PKDCURE.ORG/RESEARCH
PKD Life - Spring 2022

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