BOSTON, July 22, 2020 /PRNewswire/ -- Akcea
Therapeutics, Inc. (NASDAQ: AKCA), a majority-owned affiliate of
Ionis Pharmaceuticals, Inc., today announced that the Main
Association of Austrian Social Security Institutions (Dachverband
der Österreichischen Sozialversicherungsträger, or DV) has granted
approval for the national reimbursement of TEGSEDI® (inotersen) for
the treatment of stage 1 or stage 2 polyneuropathy in adult
patients with hereditary transthyretin (hATTR) amyloidosis.
"We are pleased that after an in-depth assessment of TEGSEDI,
the Main Association of Austrian Social Security Institutions sees
the significant unmet medical need in hATTR amyloidosis and
recognizes the demonstrated benefit of TEGSEDI for people living
with this progressing and potentially fatal disease in Austria," said Michael Pollock, SVP, head
of Europe at Akcea. "This is a significant milestone for
our team and we are excited to bring this much-needed treatment to
eligible patients in Austria."
hATTR amyloidosis is an under-recognized, debilitating and
progressive disease that is caused by the buildup of transthyretin
(TTR) proteins that misfold due to inherited genetic mutations. It
is characterized by the deposition of amyloid fibrils throughout
the body including in nervous tissue and can have a devastating
impact on patients' quality of life.
TEGSEDI is a once-weekly, at-home subcutaneous injection
that targets the polyneuropathy of hATTR amyloidosis at its source
by silencing the defective gene in these patients and reducing
production of the abnormal TTR protein. It is the first
antisense oligonucleotide medicine available for patients in
Austria with hATTR amyloidosis
with polyneuropathy and also the first treatment available that can
be self-administered in the comfort of their own home.
"Many patients in Austria have
been living with the progressive and devastating effects of this
disease for years with limited treatment options, and I am pleased
to now be able to offer them an additional option that has been
extensively studied," said Professor Wolfgang Löscher, Department of Neurology,
University Hospital Innsbruck. "Research also suggests that earlier
access to treatment for hATTR amyloidosis may help slow the
progression of the disease, making this approval of reimbursement
even more significant for the hATTR amyloidosis community in
Austria."
The positive reimbursement recommendation for TEGSEDI issued by
the Main Association of Austrian Social Security Institutions was
based on results from the Phase 3 NEURO-TTR study of the therapy in
patients with hATTR amyloidosis with symptoms of polyneuropathy.
Data from the study showed that patients treated with TEGSEDI
experienced significant benefit compared to patients treated with
placebo across both co-primary endpoints: the Norfolk Quality of
Life Questionnaire-Diabetic Neuropathy (Norfolk QoL-DN) and
modified Neuropathy Impairment Score +7 (mNIS+7), a measure of
neuropathic disease progression.
In 2018, TEGESDI was the first RNA-targeted therapeutic approved
by the European Commission for adult patients with hATTR
amyloidosis. Since then, TEGSEDI has continued to receive
regulatory and reimbursement approvals globally, most recently
gaining reimbursement approvals in Italy and Portugal.
ABOUT TEGSEDI® (INOTERSEN)
TEGSEDI was approved by the U.S. Food and Drug
Administration (FDA) for the treatment of the polyneuropathy
of hereditary transthyretin-mediated (hATTR) amyloidosis in adults.
TEGSEDI, discovered and developed by Ionis Pharmaceuticals, is
the world's first and only subcutaneous RNA-targeting drug designed
to reduce the production of human transthyretin (TTR) protein.
TEGSEDI also received marketing authorization in the European
Union and Canada for the
treatment of stage 1 or stage 2 polyneuropathy in adult patients
with hereditary transthyretin amyloidosis.
The approval is based on data from the NEURO-TTR study that was
a Phase 3 randomized (2:1), double-blind, placebo-controlled,
15-month, international study in 172 patients with hATTR
amyloidosis with symptoms of polyneuropathy. In NEURO-TTR, TEGSEDI
demonstrated significant improvement compared to placebo in
measures of neuropathy and quality of life as measured by the
modified Neuropathy Impairment Score +7 (mNIS+7) and in the Norfolk
Quality of Life Questionnaire-Diabetic Neuropathy (Norfolk QOL-DN)
total score. Patients treated with TEGSEDI experienced similar
benefit regardless of subgroups such as age, sex, race, region,
Neuropathy Impairment Score (NIS), Val30Met mutation status, and
disease stage.
The approval is also based on data from the NEURO-TTR Open Label
Extension (OLE) that is an ongoing study for patients who completed
the NEURO-TTR study, designed to evaluate the long-term efficacy
and safety of TEGSEDI.
For TEGSEDI's full prescribing information, please
visit www.TEGSEDI.com.
IMPORTANT SAFETY INFORMATION
BOXED WARNING: THROMBOCYTOPENIA AND
GLOMERULONEPHRITIS
Thrombocytopenia
- TEGSEDI causes reductions in platelet count that may result
in sudden and unpredictable thrombocytopenia, which can be
life-threatening. One clinical trial patient died from intracranial
hemorrhage
- TEGSEDI is contraindicated in patients with a platelet count
below 100 x 109 /L
- Prior to starting TEGSEDI, obtain a platelet count. During
treatment, monitor platelet counts weekly if values are 75 x
109 /L or greater, and more frequently if values are
less than 75 x 109 /L
- If a patient develops signs or symptoms of thrombocytopenia,
obtain a platelet count as soon as possible. The patient should not
receive additional TEGSEDI unless a platelet count is determined to
be interpretable and acceptable by a medical professional
- Following discontinuation of treatment for any reason,
continue to monitor platelet count for 8 weeks, or longer if
platelet counts are less than normal, to verify that platelet
counts remain above 75 x 109 /L
Glomerulonephritis
- TEGSEDI can cause glomerulonephritis that may require
immunosuppressive treatment and may result in dialysis-dependent
renal failure. One clinical trial patient who developed
glomerulonephritis and did not receive immunosuppressive treatment
remained dialysis dependent. In clinical trials, cases of
glomerulonephritis were accompanied by nephrotic syndrome, which
can have manifestations of edema, hypercoagulability with venous or
arterial thrombosis, and increased susceptibility to
infection
- TEGSEDI should generally not be initiated in patients with
urinary protein to creatinine ratio (UPCR) of 1000 mg/g or
higher
- Prior to starting TEGSEDI, measure the serum creatinine,
estimated glomerular filtration rate (eGFR), urine protein to
creatinine ratio (UPCR), and perform a urinalysis. During
treatment, monitor serum creatinine, eGFR urinalysis, and UPCR
every 2 weeks. TEGSEDI should not be given to patients who develop
a UPCR of 1000 mg/g or higher or eGFR below 45
mL/minute/1.73 m2, pending
further evaluation of the cause
- If a dose is held, once eGFR increases to ≥45
mL/minute/1.73 m2, UPCR
decreases to below 1000 mg/g, or the underlying cause of the
decline in renal function is corrected, weekly dosing may be
reinitiated. In patients with UPCR of 2000 mg/g or higher, perform
further evaluation for acute glomerulonephritis, as clinically
indicated. If acute glomerulonephritis is confirmed, TEGSEDI should
be permanently discontinued
TEGSEDI REMS Program
- Because of the risks of serious bleeding caused by severe
thrombocytopenia and because of glomerulonephritis, both of which
require frequent monitoring, TEGSEDI is available only through a
restricted distribution program under a Risk Evaluation and
Mitigation Strategy (REMS) called the TEGSEDI REMS Program
CONTRAINDICATIONS
TEGSEDI is contraindicated in patients with
- Platelet count below 100 x 109 /L
- History of acute glomerulonephritis caused by TEGSEDI
- History of a hypersensitivity reaction to TEGSEDI
WARNINGS AND PRECAUTIONS
Thrombocytopenia
TEGSEDI causes reductions in platelet count that may result in
sudden and unpredictable thrombocytopenia that can be
life-threatening. In Study 1, platelet counts below 100 x
109 /L occurred in 25% of TEGSEDI-treated patients
compared with 2% of patients on placebo. Platelet counts below 75 x
109 /L occurred in 14% of TEGSEDI-treated patients
compared with no patients on placebo. One patient in a clinical
trial experienced a fatal intracranial hemorrhage. Do not initiate
TEGSEDI in patients with a platelet count below 100 x
109 /L. Follow recommended monitoring and treatment
recommendations for platelet count.
Symptoms of thrombocytopenia can include unusual or prolonged
bleeding (eg, petechiae, easy bruising, hematoma, subconjunctival
bleeding, gingival bleeding, epistaxis, hemoptysis, irregular or
heavier than normal menstrual bleeding, hematemesis, hematuria,
hematochezia, melena), neck stiffness, or atypical severe headache.
Patients and caregivers should be instructed to be vigilant for
symptoms of thrombocytopenia and seek immediate medical help if
they have concerns.
Glomerulonephritis and Renal Toxicity
TEGSEDI can cause glomerulonephritis that may result in
dialysis-dependent renal failure. In Study 1, glomerulonephritis
occurred in 3 (3%) TEGSEDI-treated patients compared with no
patients on placebo. One patient did not receive immunosuppressive
treatment and remained dialysis-dependent. If glomerulonephritis is
suspected, pursue prompt diagnosis and initiate immunosuppressive
treatment as soon as possible. Follow recommended monitoring and
treatment recommendations for renal parameters. TEGSEDI should
generally not be initiated in patients with a UPCR of 1000 mg/g or
greater. If acute glomerulonephritis is confirmed, TEGSEDI should
be permanently discontinued.
TEGSEDI is available only through a restricted program under
a Risk Evaluation and Mitigation Strategy (REMS) called the TEGSEDI
REMS Program because of risks of serious bleeding caused by severe
thrombocytopenia and because of glomerulonephritis.
Stroke and Cervicocephalic Arterial Dissection
TEGSEDI may cause stroke and cervicocephalic arterial
dissection. In clinical studies, 1 of 161 (0.6%) TEGSEDI-treated
patients experienced carotid artery dissection and stroke. Educate
patients on the symptoms of stroke and central nervous system
arterial dissection. Instruct patients to seek help as soon as
possible if symptoms of stroke or arterial dissection occur.
Inflammatory and Immune Effects
Inflammatory and immune changes are an effect of some antisense
oligonucleotide drugs, including TEGSEDI. In clinical studies,
serious inflammatory and immune adverse reactions occurred in
TEGSEDI treated patients, including immune thrombocytopenia and
glomerulonephritis, as well as a single case of antineutrophil
cytoplasmic autoantibody (ANCA)–positive systemic vasculitis.
Liver Injury
In clinical studies, 8% of TEGSEDI-treated patients had an
increased alanine aminotransferase (ALT) at least 3 times the upper
limit of normal (ULN) compared with 3% of patients on placebo; 3%
of TEGSEDI treated patients had an ALT at least 8 times the ULN
compared with no patients on placebo. Monitor ALT, aspartate
aminotransferase, and total bilirubin at baseline and every 4
months during treatment with TEGSEDI. If a patient develops
clinical signs or symptoms suggestive of hepatic dysfunction,
promptly measure serum transaminases and total bilirubin and
interrupt or discontinue treatment with TEGSEDI, as
appropriate.
Liver Transplant Rejection
In a clinical study, cases of liver transplant rejection were
reported 2-4 months after starting TEGSEDI in patients whose liver
allografts had previously been clinically stable (for over 10
years) prior to starting TEGSEDI. In these cases, the patients
clinically improved and transaminase levels normalized after
glucocorticoid administration and cessation of TEGSEDI.
In patients with a history of liver transplant, monitor ALT,
AST, and total bilirubin monthly. Discontinue TEGSEDI in patients
who develop signs of liver transplant rejection.
Hypersensitivity Reactions/Antibody Formation
TEGSEDI can cause hypersensitivity reactions. In clinical
studies, 6 of 161 (4%) TEGSEDI-treated patients stopped treatment
because of a hypersensitivity reaction. These reactions generally
occurred within 2 hours of administration of TEGSEDI. Antibodies to
TEGSEDI were present when the reactions occurred. If a
hypersensitivity reaction occurs, discontinue administration of
TEGSEDI and initiate appropriate therapy. Do not use in patients
who have a history of hypersensitivity reactions to TEGSEDI.
Uninterpretable Platelet Counts: Reaction Between
Antiplatelet Antibodies and Ethylenediaminetetraacetic acid
(EDTA)
In Study 1, 23% of TEGSEDI-treated patients had at least 1
uninterpretable platelet count caused by platelet clumping compared
with 13% of patients on placebo. If there is suspicion of
EDTA-mediated platelet clumping, perform a repeat platelet count
using a different anticoagulant (eg, sodium citrate, heparin) in
the blood collection tube. Recheck the platelet count as soon as
possible if a platelet measurement is uninterpretable. Hold TEGSEDI
dosing until an acceptable platelet count is confirmed with an
interpretable blood sample.
Reduced Serum Vitamin A Levels and Recommended
Supplementation
TEGSEDI treatment leads to a decrease in serum vitamin A levels.
Supplementation at the recommended daily allowance of vitamin A is
advised for patients taking TEGSEDI. Patients should be referred to
an ophthalmologist if they develop ocular symptoms suggestive of
vitamin A deficiency (eg, night blindness).
ADVERSE REACTIONS
The most common adverse reactions that occurred in at least 20%
of TEGSEDI-treated patients and more frequently than in those on
placebo were injection site reactions, nausea, headache, fatigue,
thrombocytopenia, and fever. Serious adverse reactions were more
frequent in TEGSEDI-treated patients (32%) than in patients on
placebo (21%).
DRUG INTERACTIONS
Because of the risk of thrombocytopenia, caution should be used
when using antiplatelet drugs (including nonprescription products
that affect platelets) or anticoagulants concomitantly with
TEGSEDI. Because of the risk of glomerulonephritis and renal
toxicity, caution should be used when using nephrotoxic drugs and
other drugs that may impair renal function concomitantly with
TEGSEDI.
Please see full Prescribing Information, including boxed
WARNING, at TEGSEDIhcp.com.
ABOUT HEREDITARY TRANSTHYRETIN (hATTR)
AMYLOIDOSIS
Hereditary ATTR amyloidosis is a severe,
progressive, and life-threatening disease caused by the abnormal
formation of the TTR protein and aggregation of TTR amyloid
deposits in various tissues and organs throughout the body,
including in peripheral nerves, the heart and intestinal tract. The
progressive accumulation of TTR amyloid deposits in these organs
often leads to intractable peripheral sensorimotor neuropathy,
autonomic neuropathy, and/or cardiomyopathy, as well as other
disease manifestations. Hereditary ATTR amyloidosis causes
significant morbidity and progressive decline in quality of life,
severely impacting activities of daily living. The disease often
progresses rapidly and can lead to premature death. The median
survival is 4.7 years following diagnosis. Additional information
on hereditary ATTR amyloidosis, including a full list of
organizations supporting the hATTR amyloidosis community worldwide,
is available at www.hattrchangethecourse.com or by
visiting www.hATTRGuide.com.
ABOUT AKCEA THERAPEUTICS, INC.
Akcea Therapeutics, Inc., a majority-owned affiliate
of Ionis Pharmaceuticals, Inc. (NASDAQ: IONS), is a
biopharmaceutical company focused on developing and commercializing
medicines to treat patients with serious and rare diseases. Akcea
is commercializing TEGSEDI® (inotersen) and
WAYLIVRA® (volanesorsen), as well as advancing a
mature pipeline of novel medicines, including
AKCEA-APO(a)-LRx, vupanorsen
(AKCEA-ANGPTL3-LRx), AKCEA-APOCIII-LRx, and
AKCEA-TTR-LRx, with the potential to treat multiple
diseases. All six medicines were discovered by Ionis, a leader in
antisense therapeutics, and are based on Ionis' proprietary
antisense technology. TEGSEDI is approved in the U.S., E.U.,
Canada and Brazil, and WAYLIVRA is approved in the
E.U. Akcea is headquartered in Boston,
Massachusetts, and is building the infrastructure to
commercialize its medicines globally. Additional information about
Akcea is available at www.akceatx.com and you can follow
us on Twitter at @akceatx.
FORWARD-LOOKING STATEMENT
This press release includes forward-looking statements regarding
the business of Akcea Therapeutics, Inc. Any statement
describing Akcea's goals, expectations, financial or other
projections, intentions or beliefs, including the commercial
potential of Akcea's medicines in development is a forward-looking
statement and should be considered an at-risk statement. Such
statements are subject to certain risks and uncertainties,
particularly those inherent in the process of discovering,
developing and commercializing medicines that are safe and
effective for use as human therapeutics, and in the endeavor of
building a business around such medicines. Akcea's forward-looking
statements also involve assumptions that, if they never materialize
or prove correct, could cause its results to differ materially from
those expressed or implied by such forward-looking statements.
Although Akcea's forward-looking statements reflect the good faith
judgment of its management, these statements are based only on
facts and factors currently known by Akcea. In particular, we
caution you that our forward-looking statements are subject to the
ongoing and developing circumstances related to the COVID-19
pandemic, which may have a material adverse effect on our business,
operations and future financial results. As a result, you are
cautioned not to rely on these forward-looking statements. These
and other risks concerning Akcea's programs are described in
additional detail in Akcea's quarterly reports on Form 10-Q and
annual reports on Form 10-K, which are on file with the SEC.
Copies of these and other documents are available from the
company.
In this press release, unless the context requires otherwise,
"Ionis", "Akcea," "Company," "Companies" "we," "our," and "us"
refers to Ionis Pharmaceuticals and/or Akcea
Therapeutics.
Ionis Pharmaceuticals™ is a trademark of Ionis
Pharmaceuticals, Inc. Akcea Therapeutics®,
TEGSEDI® and WAYLIVRA® are
trademarks of Akcea Therapeutics, Inc.
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