PKD Life - Summer 2021 - 22

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THE RESEARCH REPORT
ARPKD
Research
What's in the pipeline?
By Debra Gordon
W hen tolvaptan was approved for adults with
autosomal dominant polycystic kidney disease
autosomal dominant polycystic kidney disease
(ADPKD) in 2018, some in the PKD community had a
question: When will those with the autosomal recessive
form of the disease (ARPKD) also have a treatment?
The answer is, well, complicated.
The only clinical trial conducted so far in patients
with ARPKD was a phase 1 study to evaluate the safety
of the tyrosine kinase inhibitor tesevatinib. Although it
is completed, no results have been released publicly.
However, two phase 3 studies of tolvaptan in patients
with ARPKD are launching soon. One is designed to
evaluate the safety, tolerability, and effi cacy of tolvaptan
in children ages 1 month to 18 years. The other is
designed to see whether the drug can delay the need
for dialysis in infants ages 1 to 3 months.
WHY SO LITTLE PROGRESS IN ARPKD?
" I see three main barriers to getting drugs to clinical
trials for this disease, " says Erum Hartung, M.D., M.T.R.,
who co-directs the Kidney/Liver Program at Children's
Hospital of Philadelphia. The fi rst is a knowledge gap
about the natural history of the disease, which presents
and progresses so diff erently in patients.
" ARPKD is such a rare disease that it's diffi cult to
get good natural history data, " she says. " But to go to
a clinical trial, you need a full understanding of the
breadth of the disease, what the range of possible outcomes
is in diff erent people. " That's important because
22 PKD LIFE * SUMMER 2021
the disease is so variable. It
can be fatal in some newborns,
while other children
aren't diagnosed until adolescence
or later. " We need to
be able to identify who might
benefi t from a clinical trial
versus those who would have
done OK without complications
anyway. "
Researchers are making
progress in this area, however,
thanks to registries such as
the ARegPKD registry based in
Germany and the ARPKD database
out of Children's National
Hospital in Washington, DC.
The second barrier to
clinical trials is deciding what
to measure to determine
whether the drug is working.
While blood tests such as
creatinine and cystatin C are
good measures of kidney
function, Dr. Hartung says,
" the challenge in ARPKD is
that sometimes these blood
tests don't change much over
the course of a few years. "
Indeed, in some people it
takes many years for kidney
function to decline to the
point that it shows up on the
tests, but clinical trials are
typically designed for only
two or three years.
That problem was helped in
the ADPKD population by the
use of MRI to measure kidney
volume and cyst growth. However,
the same MRI methods
won't work with ARPKD, Dr.
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PKD Life - Summer 2021

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