CARLSBAD, Calif., Jan. 8, 2018 /PRNewswire/ -- Ionis
Pharmaceuticals, Inc. (NASDAQ: IONS) announced today that its New
Drug Application (NDA) for inotersen has been accepted for Priority
Review by the U.S. Food and Drug Administration (FDA). Inotersen is
an investigational drug for the treatment of patients with
hereditary TTR amyloidosis (hATTR). Priority Review is granted by
the FDA to drugs with the potential to address a serious condition
and, if approved, would provide a significant improvement in safety
or effectiveness of the treatment, prevention, or diagnosis of a
serious condition. The FDA has set a Prescription Drug User Fee Act
(PDUFA) date of July 6, 2018.
"TTR amyloidosis is a progressive, fatal disease with very
limited treatment options. Receiving Priority Review in the U.S.
and Accelerated Assessment in the EU for inotersen shows that the
regulatory agencies recognize the high unmet need and the urgency
to identify effective therapies to treat patients with this
devastating disease," said Sarah
Boyce, chief business officer of Ionis Pharmaceuticals. "We
continue our launch preparations for inotersen and are on track to
launch inotersen promptly in the U.S. and EU if approved."
"We have been working closely with both the FDA and the EMA
following the completion of our Phase 3 study to expedite the
regulatory review timelines for inotersen," said Brett Monia, Ph.D., senior vice president of
drug discovery and franchise leader for oncology and rare diseases
at Ionis Pharmaceuticals. "Today's outcome reflects our strong
relationship with regulators and the quality and completeness of
our regulatory submissions. It also reflects the potential for
inotersen to serve a major unmet medical need based on the results
of our Phase 3 study, which demonstrated early and sustained
benefit to patients treated with inotersen in multiple aspects of
their disease, including quality of life."
ABOUT INOTERSEN
Inotersen is an antisense drug designed to reduce the production of
transthyretin, or TTR, to treat patients with TTR amyloidosis
(ATTR), a severe, rare and fatal disease. In patients with ATTR,
both the mutant and wild-type (wt) TTR builds up as fibrils in
tissues, such as the peripheral nerves, heart, gastrointestinal
system, eyes, kidneys, central nervous system, thyroid and bone
marrow. The presence of TTR fibrils interferes with the normal
functions of these tissues. As the TTR protein fibrils enlarge,
more tissue damage occurs and the disease worsens, resulting in
poor quality of life and eventually death.
The FDA previously granted inotersen Orphan Drug Designation and
Fast Track Status. A Marketing Authorization Application (MAA) has
been submitted to the European Medicines Agency, which has
granted Accelerated Assessment and Orphan Drug Designation to
inotersen for the treatment of patients with ATTR.
ABOUT INOTERSEN PHASE 3 CLINICAL STUDY
Inotersen completed a Phase 3 study, NEURO-TTR, in patients with
polyneuropathy due to hereditary TTR amyloidosis (hATTR)
in May 2017. Results from the study demonstrated 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, consistent and
significant benefit was observed in both the Norfolk-QoL-DN and
mNIS+7, independent of disease stage, types of mutation, previous
treatment with TTR protein stabilizers or presence of
cardiomyopathy at the beginning of the study. Inotersen-treated
patients benefited significantly in the quality of life primary
endpoint with 50% of patients experiencing improved scores compared
to baseline and 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). In
addition, clinically meaningful benefit compared to placebo was
observed in the SF-36 physical component score, a measure of
general health quality of life. Inotersen-treated patients also
benefited significantly in the co-primary endpoint of disease
control, mNIS+7, with 47% of patients experiencing improved or
stable scores compared to baseline and a mean difference in
magnitude of 19.73 -points, compared to placebo-treated patients,
at 15 months of treatment, (p < 0.001).
Two key safety issues were identified during the study:
thrombocytopenia and safety signals related to renal function.
Enhanced monitoring was implemented during the study to support
early detection and management of these issues. Serious platelet
and renal events were infrequent and easily managed with routine
monitoring, which has proven effective since implementation. Other
serious adverse events were observed in 24.1% of inotersen-treated
patients and 21.7% of placebo-treated patients. No cumulative
toxicities have been identified with long-term exposure.
Adverse events occurring in >=10% of patients and twice as
frequently in inotersen-treated patients compared with
placebo-treated patients included thrombocytopenia/platelet count
decreases, nausea, pyrexia, chills, vomiting, and anemia. Injection
site reactions accounted for less than 1% of all injections and
were mild or moderate in severity. There were no discontinuations
due to injection site reactions. The overall mortality rate in the
NEURO-TTR study was 2.9% and was lower than overall mortality rates
reported in other studies in hATTR patients. There were a total of
five deaths in the study, five (4.7%) in the inotersen arm and zero
in the placebo arm. Four deaths in the inotersen arm 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.
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 three
dozen 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. Drugs that have successfully completed
Phase 3 studies include inotersen, an antisense drug Ionis is
developing to treat patients with hereditary TTR amyloidosis
(hATTR), and volanesorsen, an antisense drug discovered by Ionis
and co-developed by Ionis and Akcea Therapeutics to treat
patients with either familial chylomicronemia syndrome or familial
partial lipodystrophy. Akcea, an affiliate of Ionis, is a
biopharmaceutical company focused on developing and commercializing
drugs to treat patients with serious cardiometabolic diseases
caused by lipid disorders. If approved, volanesorsen will be
commercialized through Ionis' affiliate, Akcea. Inotersen filings
for marketing approval are under review in the U.S. and
EU. Volanesorsen filings for marketing approval are under
review in the U.S., EU, and Canada. Ionis' patents provide strong and
extensive protection for its drugs and technology. Additional
information about Ionis is available
at www.ionispharma.com.
IONIS' FORWARD-LOOKING STATEMENT
This press release
includes forward-looking statements regarding the therapeutic and
commercial potential of inotersen and other products in
development. Any statement describing Ionis' goals, expectations,
financial or other projections, intentions or beliefs 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. 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 Ionis' forward-looking statements reflect the good faith
judgment of its management, these statements are based only on
facts and factors currently known by Ionis. As a result, you are
cautioned not to rely on these forward-looking statements. These
and other risks concerning Ionis' programs are described in
additional detail in Ionis' annual report on Form 10-K for the year
ended December 31, 2016, and its most
recent quarterly report on Form 10-Q, 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," "Company," "we," "our," and "us" refers to Ionis
Pharmaceuticals and its subsidiaries.
Ionis Pharmaceuticals™ is a trademark of Ionis Pharmaceuticals,
Inc. Akcea Therapeutics™ is a trademark of Ionis Pharmaceuticals,
Inc. SPINRAZA® is a registered trademark of Biogen.
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SOURCE Ionis Pharmaceuticals, Inc.