Hospital Pharmacy - July/August 2018 - 236

779757
research-article2018

HPXXXX10.1177/0018578718779757Hospital PharmacyWalker

Pharmaceutical Pipeline Update

New Medications in the Treatment of
Hereditary Transthyretin Amyloidosis

Hospital Pharmacy
2018, Vol. 53(4) 236-238
© The Author(s) 2018
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https://doi.org/10.1177/0018578718779757
DOI: 10.1177/0018578718779757
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Scot Walker1

Abstract
Hereditary transthyretin amyloidosis is an inherited disorder that results in the gradual progressive deposit of abnormal
protein called amyloid in the body's organs and tissues. There are currently no approved drugs to treat transthyretin
amyloidosis, and patients may require liver transplantation for survival. There are a few drugs in development to treat
hereditary transthyretin amyloidosis either by stabilizing the abnormal protein or by decreasing production of transthyretin.
Both methods are being developed to slow progression of the disease.
Keywords
formulary management / P & T, drug information, investigational drugs

Epidemiology
Transthyretin (TTR) is a protein found in serum and cerebrospinal fluid, where it transfers thyroxine and retinol. Hereditary
transthyretin (hATTR) amyloidosis is an inherited disorder that
results in the gradual progressive deposit of abnormal protein
called amyloid in the body's organs and tissues. Most often, the
proteins are deposited in the heart, peripheral nervous system,
and central nervous system. As the disease progresses, patient's
motor skills deteriorate, and walking becomes difficult. In
advanced stages of the disease, patients develop neuropathies,
gastrointestinal (GI) impairment, and weight loss that can be
life-threatening.1 It is estimated that approximately 50 000 people worldwide have hATTR amyloidosis.2 The median survival
for patients with a hATTR amyloidosis diagnosis depends on
organ system involvement. When neurologic involvement is
dominant, survival is estimated to be 5 to 15 years, but cardiac
involvement indicates reduced survival of 2.5 to 4 years.1
Researchers in Portugal estimated the lifetime costs for health
care to be $154 819 per untreated hATTR polyneuropathy
patient.3 An analysis of liver transplantation costs estimated a
cost of $1 427 805 per patient for a liver transplantation. This
would profoundly increase the lifetime cost in patients who
receive a liver transplant.4

Current Treatment
There are currently very limited choices in the treatment of
hATTR amyloidosis. There are no treatments for prevention
or reversal of the disease. Symptomatic treatment is the first
line of treatment.1
Transthyretin proteins are produced in the liver. To inhibit
or stop the creation of abnormal amyloids, patients may

receive a liver transplantation.5 This is sometimes combined
with kidney or heart transplantation depending on organ
damage.6 Limits in organ availability and the possibility of
disease progression in other organs after liver transplantation
limits the use of transplants.
Diflunisal complexes with thyroxine binding sites, which
stabilizes circulating TTR tetramers.7 This leads to an inhibition of the TTR monomer used in amyloidogenesis. In a
2-year, 130 patient, phase III trial, diflunisal reduced the rate
of neurological progression and improved the quality of life
in patients with familial amyloid polyneuropathy.8 Due to the
adverse effect profile of nonsteroidal anti-inflammatory
drugs, there is an increased risk for GI, cardiac, and nephron
toxicity.1 In the phase III diflunisal trial, there was an increase
in GI events, but not renal or cardiac events.8

New Treatment Options
Tafamidis is approved in Europe to slow disease progression.
The Food and Drug Administration rejected the drug in 2012
due to a limited efficacy data. Tafamidis stabilizes TTR,
which delays progression of hATTR. In an 18-month, 128
patient, phase III trial, tafamidis improved the Neuropathy
Impairment Score compared with placebo in patients with
TTR polyneuropathy.9 The drug was shown to slow disease
progression for up to 5.5 years in a 71-patient extension of
1

Prescribe Right, LLC, Wildwood, MO, USA

Corresponding Author:
Scot Walker, Chief Executive Officer, Prescribe Right, LLC, 1602
Westglen Farms Dr, Wildwood, MO 63011, USA.
Email: scot.walker@prescriberight.com
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