CARLSBAD, Calif., and
CAMBRIDGE, Mass., July 5, 2018 /PRNewswire/ -- Ionis
Pharmaceuticals, Inc. (Nasdaq: IONS), the leader in antisense
therapeutics, and its affiliate, Akcea Therapeutics (Nasdaq: AKCA),
announced today that the final study results from NEURO-TTR, the
pivotal study of TEGSEDI™ (inotersen) in patients with hereditary
ATTR (hATTR) amyloidosis with polyneuropathy, were published in the
July 5, 2018 issue of The New
England Journal of Medicine in a manuscript titled
"Inotersen Treatment for Patients with Hereditary Transthyretin
Amyloidosis."
Results from the study demonstrated that patients treated with
TEGSEDI experienced early, sustained and highly significant benefit
in both co-primary endpoints: the modified Neuropathy
Impairment Score +7 (mNIS+7), a measure of neuropathic disease
progression, and the Norfolk Quality of Life Questionnaire-Diabetic
Neuropathy (Norfolk QoL-DN), compared to placebo-treated patients.
Furthermore, a substantial number of TEGSEDI-treated patients
displayed improvements in disease symptoms as measured in both
co-primary endpoints, compared to their baseline study entry
values. The clinical benefits demonstrated by TEGSEDI were
associated with substantial reductions in the transthyretin (TTR)
protein, the underlying cause of hATTR amyloidosis. For the
full text of this publication, please visit:
https://www.nejm.org/doi/full/10.1056/NEJMoa1716793.
"hATTR amyloidosis is a progressive, systemic and fatal disease
that relentlessly deprives people of their independence and
dignity. People with hATTR amyloidosis experience misfolded TTR
build up in various tissues and organs, resulting in progressively
debilitating symptoms which lead to death within a few years of
symptom onset," said Morie Gertz,
M.D., Roland Seidler Jr. Professor
of the Art of Medicine and chair of the department of Internal
Medicine at the Mayo Clinic. "Unfortunately, currently available
therapeutic options are inadequate to slow the progression of hATTR
amyloidosis. I am encouraged with the benefit in neuropathy
symptoms and quality of life observed in patients treated with
TEGSEDI in this Phase 3 study. I believe TEGSEDI has promising
potential to treat patients with this devastating disease."
"Based on these study results and the feedback we have received
from physicians and patients, we believe TEGSEDI has the potential
to provide people living with hATTR amyloidosis a greater degree of
control over their disease and their lives together with the
convenience of a once weekly, self-administered subcutaneous
injection," said Sarah Boyce,
president of Akcea Therapeutics. "The regulatory reviews in the
U.S. and EU are progressing well and we anticipate approval soon,
bringing us one step closer to achieving our mission to transform
the lives of people with hATTR amyloidosis. We understand the
urgent need for new treatments for this disease and are ready to
launch TEGSEDI."
"We believe the NEURO-TTR Phase 3 results demonstrate a
favorable benefit-risk profile for TEGSEDI to treat patients with
this devastating disease. Patients treated with TEGSEDI experienced
substantial improvements in measures of neuropathy and quality of
life compared to placebo-treated patients, independent of TTR
mutation type, disease stage or presence of cardiomyopathy.
Remarkably, half of the TEGSEDI-treated patients in this study
experienced improvement in their quality of life over the course of
their treatment and nearly 40% improved in a measure of
neurological disease progression," said Brett P. Monia, Ph.D.,
chief operating officer, senior vice president of antisense drug
discovery and translational medicine at Ionis Pharmaceuticals.
ABOUT NEURO-TTR: TEGSEDI PHASE 3 CLINICAL STUDY
The
NEURO-TTR study was a Phase 3 randomized (2:1), double-blind,
placebo-controlled, international study in 172 patients with
polyneuropathy due to hATTR amyloidosis. The 15-month study
measured the effects of treatment with TEGSEDI on neurological
dysfunction and on quality-of-life by measuring the change from
baseline both in the modified Neuropathy Impairment Score +7
(mNIS+7) and in the Norfolk Quality of Life Questionnaire-Diabetic
Neuropathy (Norfolk QOL-DN) total score. The NEURO-TTR OLE is an
ongoing study for patients who completed the NEURO-TTR study and is
intended to evaluate the long-term efficacy and safety profile of
TEGSEDI.
In the NEURO-TTR study, patients treated with TEGSEDI
experienced benefit compared to placebo across both primary
endpoints of the study: the Norfolk Quality of Life
Questionnaire-Diabetic Neuropathy (Norfolk QoL-DN) and the modified
Neuropathy Impairment Score +7 (mNIS+7) at both eight and 15 months
of treatment. In addition, patients treated with TEGSEDI
experienced significant benefit in both the Norfolk-QoL-DN and
mNIS+7, independent of disease stage, types of mutation or presence
of cardiomyopathy. Most TEGSEDI-treated patients experienced
substantial reductions in TTR. Nearly 90% of patients achieved
>50% TTR reduction and nearly 50% achieved over 75% TTR
reduction at 15 months. Median TTR reduction was 79% at Week 65.
These TTR reductions were associated with improvements from
baseline in the Norfolk QoL-DN primary endpoint with a mean
difference in magnitude of 11.68 points, compared to
placebo-treated patients, at 15 months of treatment (mean change
from baseline of 0.99 vs. 12.67, p<0.001). 50% of
TEGSEDI-treated patients had improved Norfolk QoL scores compared
to their baseline scores. Clinically meaningful benefit was also
observed in TEGSEDI-treated patients compared to placebo-treated
patients in the SF-36 physical component score, a measure of
general health quality of life. In addition, TEGSEDI-treated
patients benefited significantly in the co-primary endpoint
assessing disease control, the mNIS+7, achieving a mean difference
in magnitude of 19.73-points, compared to placebo-treated patients,
at 15 months of treatment (mean change from baseline of 5.80 vs.
25.53, p<0.001). 36.5% of TEGSEDI-treated patients had improved
mNIS+7 scores compared to their baseline scores. As previously
reported, encouraging benefit was also observed in TEGSEDI-treated
patients with significant cardiac disease at baseline
(interventricular septum thickness, IVS ≥ 1.5 cm) in multiple
cardiac measures, including mean decreases in left ventricle mass
(p=0.0288), IVS (p=0.0150) and posterior wall thickness (p=0.0425),
which increased, on average, in placebo-treated patients.
Thrombocytopenia and safety signals related to renal function
were identified during the study. Enhanced monitoring was
implemented during the study to support early detection and
management of these issues. Serious platelet and renal events were
infrequent and manageable with routine monitoring, which has proven
effective since implementation.
Adverse events occurring in >=10% of patients and twice as
frequently in TEGSEDI-treated patients compared with
placebo-treated patients included thrombocytopenia/platelet count
decreases, nausea, pyrexia, chills, vomiting, and anemia. Injection
site reactions were observed in about 1% of all injections and were
mild or moderate in severity. There were no discontinuations due to
injection site reactions. There were five deaths in the study, five
(4.5%) in the TEGSEDI arm and zero in the placebo arm. The
mortality rate in the drug-treatment arm is comparable to the death
rate expected in this patient population as evidenced in other
clinical trials. Four deaths were associated with disease
progression and considered unrelated to treatment. As previously
reported, there was one fatal intracranial hemorrhage in
conjunction with serious thrombocytopenia. No serious
thrombocytopenia was observed following implementation of more
frequent monitoring in the NEURO-TTR study.
ABOUT TEGSEDI (inotersen)
TEGSEDI™ (inotersen) is an
antisense drug designed to reduce the production of transthyretin,
or TTR protein, to treat ATTR amyloidosis, a systemic, progressive
and fatal disease. TEGSEDI is currently under regulatory review for
marketing approval in the U.S., EU and Canada. The U.S. Food and Drug Administration
has granted TEGSEDI Orphan Drug Designation and Fast Track Status,
and the European Medicines Agency has granted TEGSEDI Orphan Drug
Designation. In the U.S., TEGSEDI has a PDUFA date of October 6, 2018. The Committee for Medicinal
Products for Human Use (CHMP) of the European Medicines Agency
(EMA) adopted a positive opinion recommending approval of TEGSEDI
for the treatment of Stage 1 or Stage 2 polyneuropathy in adult
patients with hereditary transthyretin amyloidosis (hATTR). The
TEGSEDI expanded access program (EAP) has been initiated for
eligible patients in the U.S. Click here for more information on
the TEGSEDI EAP.
ABOUT HEREDITARY ATTR (hATTR) AMYLOIDOSIS
hATTR
amyloidosis is a progressive, systemic and fatal hereditary disease
caused by the inappropriate formation and aggregation of TTR
amyloid deposits in various tissues and organs throughout the body,
including in peripheral nerves, heart, intestinal tract, eyes,
kidneys, central nervous system, thyroid and bone marrow. The
progressive accumulation of TTR amyloid deposits in these tissues
and organs leads to sensory, motor and autonomic dysfunction often
having debilitating effects on multiple aspects of a patient's
life. People with hATTR amyloidosis often present with a mixed
phenotype and experience overlapping symptoms of polyneuropathy and
cardiomyopathy. People with hATTR with symptoms of polyneuropathy
are classified into 3 stages: Stage 1 patients do not require
assistance with ambulation, Stage 2 patients do require assistance
with ambulation and Stage 3 patients are confined to a wheelchair
or are bedridden.
Ultimately, hATTR amyloidosis results in death within three to
fifteen years of symptom onset. Therapeutic options for the
treatment of patients with hATTR amyloidosis are limited and there
are currently no disease-modifying drugs approved for the disease.
There are an estimated 50,000 patients with hATTR amyloidosis
worldwide. Additional information on hATTR amyloidosis,
including a full list of organizations supporting the hATTR
amyloidosis community worldwide, is available at
www.hattrchangethecourse.com.
ABOUT AKCEA THERAPEUTICS
Akcea Therapeutics, Inc., an
affiliate of Ionis Pharmaceuticals, Inc., is a biopharmaceutical
company focused on developing and commercializing drugs to treat
patients with serious and rare diseases. Akcea is advancing a
mature pipeline of six novel drugs, including TEGSEDI™ (inotersen),
WAYLIVRA™ (volanesorsen), AKCEA-APO(a)-LRx,
AKCEA-ANGPTL3-LRx, AKCEA-APOCIII-LRx, and
AKCEA-TTR-LRx, all with the potential to treat multiple
diseases. All six drugs were discovered by and are being
co-developed with Ionis, a leader in antisense therapeutics, and
are based on Ionis' proprietary antisense technology. TEGSEDI is
under regulatory review in the U.S., EU and Canada for the treatment of people with
hereditary transthyretin amyloidosis, or hATTR. WAYLIVRA is under
regulatory review in the U.S., EU and Canada for the treatment of familial
chylomicronemia syndrome, or FCS, and is currently in Phase 3
clinical development for the treatment of people with familial
partial lipodystrophy, or FPL. Akcea is building the infrastructure
to commercialize its drugs globally. Akcea is a global company
headquartered in Cambridge,
Massachusetts. Additional information about Akcea is
available at www.akceatx.com.
ABOUT IONIS PHARMACEUTICALS, INC.
Ionis is the leading
company in RNA-targeted drug discovery and development focused on
developing drugs for patients who have the highest unmet medical
needs, such as those patients with severe and rare diseases. Using
its proprietary antisense technology, Ionis has created a large
pipeline of first-in-class or best-in-class drugs, with over 40
drugs in development. SPINRAZA® (nusinersen) has been approved in
global markets for the treatment of spinal muscular atrophy (SMA).
Biogen is responsible for commercializing SPINRAZA. TEGSEDI™
(inotersen) and WAYLIVRA (volanesorsen) are two antisense drugs
that Ionis discovered and successfully advanced through Phase 3
studies. TEGSEDI is under regulatory review for marketing approval
in the U.S., EU and Canada for the
treatment of patients with hereditary ATTR amyloidosis, or hATTR.
WAYLIVRA is under regulatory review for marketing approval in the
U.S., EU, and Canada for the
treatment of patients with familial chylomicronemia syndrome, or
FCS. WAYLIVRA is also in a Phase 3 study in patients with familial
partial lipodystrophy, or FPL. Akcea Therapeutics, an affiliate of
Ionis focused on developing and commercializing drugs to treat
patients with serious and rare diseases, will commercialize TEGSEDI
and WAYLIVRA, if approved. Ionis' patents provide strong and
extensive protection for its drugs and technology. Additional
information about Ionis is available at www.ionispharma.com.
AKCEA'S AND IONIS' FORWARD-LOOKING STATEMENT
This
press release includes forward-looking statements regarding the
business of Akcea Therapeutics, Inc. and Ionis Pharmaceuticals,
Inc. and the therapeutic and commercial potential of TEGSEDI™. Any
statement describing Akcea's or Ionis' goals, expectations,
financial or other projections, intentions or beliefs, including
the commercial potential of TEGSEDI, WAYLIVRA or other of Akcea's
or Ionis' drugs 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 drugs that are safe and effective for use as human
therapeutics, and in the endeavor of building a business around
such drugs. Akcea's and Ionis' 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 and Ionis' forward-looking statements reflect the
good faith judgment of its management, these statements are based
only on facts and factors currently known by Akcea and Ionis.
As a result, you are cautioned not to rely on these forward-looking
statements. These and other risks concerning Ionis' and
Akcea's programs are described in additional detail in Ionis' and
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 each 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",
"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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SOURCE Ionis Pharmaceuticals, Inc.