CARLSBAD, Calif., April 22, 2015 /PRNewswire/ -- Isis
Pharmaceuticals, Inc. (NASDAQ: ISIS) announced today positive data
from an ongoing open-label extension (OLE) study of
ISIS-TTRRx in patients with familial amyloid
polyneuropathy (FAP). FAP patients completing the ongoing
Phase 3 study are eligible to enroll in this OLE study in which all
patients receive ISIS-TTRRx. An analysis conducted
on the first group of patients to reach three months of treatment
in the OLE study showed a reduction in transthyretin (TTR) protein
levels up to 92 percent with a median reduction of 78 percent
compared to patients' baseline TTR levels at entry into the Phase 3
study. Patients continue to be enrolled as they complete
dosing in the Phase 3 study. These data will be presented
today at the American Academy of Neurology meeting in Washington, DC.
"TTR amyloidosis is a devastating progressive and fatal
disease. FAP is a genetic disease in which mutations in the
TTR gene cause the TTR protein to accumulate as amyloid in tissues,
peripheral nerves and major organs, and impair their
function. The substantial reduction in TTR protein observed
in this study suggests that ISIS-TTRRx could potentially
be an important new treatment option for patients with TTR
amyloidosis who have very limited therapeutic options," said
Merrill D. Benson, M.D., professor
of medical genetics at Indiana University.
"We are encouraged by the high rate of patient retention
observed in our Phase 3 registration study and by the high rate of
enrollment in the OLE study. We believe that the convenience
of a once weekly, at home subcutaneous injection of
ISIS-TTRRx is a significant contributing factor for the
high retention rate of our Phase 3 study and for the robust
enrollment of our OLE study. In addition, a blinded safety
analysis of the ongoing Phase 3 study shows the safety and
tolerability profile we have observed to date with
ISIS-TTRRx supports continued development.
Notably, the injection site reactions were predominantly mild and
infrequent, occurring in only about 1% of all injections," said
Brett Monia, senior vice president
of drug discovery at Isis Pharmaceuticals. "The substantial
reduction in TTR protein together with our safety profile and our
high patient retention rate gives us confidence that
ISIS-TTRRx may have a significant impact on the
treatment of this disease."
In a platform presentation titled, 'A Phase 3 Study to Evaluate
ISIS-TTRRx in Patients with Transthyretin Familial
Amyloid Polyneuropathy (TTR-FAP): Study Design and Baseline
Demographics', Dr. Benson reported that in the first thirteen
patients to enter the OLE study, reductions of up to 92 percent in
TTR protein after thirteen weeks of treatment with
ISIS-TTRRx were observed. Across all patients
enrolled in the Phase 3 study, 27 TTR mutations were represented to
date, including the Val30Met mutation, which is the most common
mutation found in patients with FAP. ISIS-TTRRx is
designed to reduce all forms of TTR, including both mutant and wild
type, and therefore should provide therapeutic benefit to any FAP
patient regardless of that patient's individual TTR
mutation.
ISIS-TTRRx was also highlighted in a second platform
presentation titled, 'Development of ISIS-TTRRx for
Transthyretin Familial Amyloid Polyneuropathy (TTR-FAP)'. In
this presentation, Dr. Fred
Derosier, executive director of clinical development at Isis
Pharmaceuticals, provided an overview of the ISIS-TTRRx
program including:
- The Phase 1 study, in which ISIS-TTRRx achieved
reductions of up to 96 percent in TTR protein levels.
- The ongoing Phase 3 study is designed to assess the effects of
ISIS-TTRRx on neurological dysfunction and on quality of
life in patients with FAP. Data from this study is planned
for the first half of 2017.
- The open-label extension study of ISIS-TTRRx in
patients with FAP who have completed all fifteen months of dosing
in the Phase 3 study.
- An investigator-initiated open-label study being conducted by
Dr. Merrill Benson in patients with
familial cardiomyopathy (FAC) and senile systemic amyloidosis
(SSA). This ongoing study is designed to assess the safety,
tolerability and efficacy of ISIS-TTRRx in these
patients.
- A Phase 3 study in patients with TTR-related cardiomyopathy
that GSK anticipates initiating later this year.
- A Phase 3 study in Japan in
patients with FAP that GSK anticipates initiating later this
year.
About TTR Amyloidosis and
ISIS-TTRRx
ISIS-TTRRx is a gen 2.0+
antisense drug Isis is developing with GSK for the treatment of TTR
amyloidosis. ISIS-TTRRx is administered as a once
weekly subcutaneous injection and is designed to inhibit the
production of all forms of TTR protein, including both mutant and
wild type, offering a unique approach to treat all types of TTR
amyloidosis.
The Phase 3 study of ISIS-TTRRx is a randomized,
double-blind, placebo-controlled, international study designed to
support an application for marketing approval of
ISIS-TTRRx in patients with FAP. The fifteen month
study will measure the effects of ISIS-TTRRx on
neurological dysfunction and on quality-of-life. For further
study information, please visit www.clinicaltrials.gov and search
for the identifier number NCT01737398.
TTR amyloidosis is a severe, genetic and fatal disease in which
patients with TTR amyloidosis experience TTR build up in major
organs, including peripheral nerves, heart, intestinal tract,
kidney and bladder. Patients with FAP experience ongoing
debilitating nerve damage throughout their body resulting in the
progressive loss of motor functions, such as walking. These
patients also accumulate TTR in major organs, which progressively
impacts their function and eventually leads to death. Therapeutic
options for the treatment of FAP are very limited and there are
currently no drugs approved for the treatment of FAP in the United
States.
ABOUT ISIS PHARMACEUTICALS, INC.
Isis is exploiting
its leadership position in RNA-targeted technology to discover and
develop novel drugs for its product pipeline and for its
partners. Isis' broad pipeline consists of 38 drugs to treat
a wide variety of diseases with an emphasis on cardiovascular,
metabolic, severe and rare diseases, including neurological
disorders, and cancer. Isis' partner, Genzyme, is
commercializing Isis' lead product, KYNAMRO®, in
the United States and other
countries for the treatment of patients with homozygous FH.
Isis has numerous drugs in Phase 3 development in severe/rare
diseases and cardiovascular diseases. These include
ISIS-APOCIIIRx, a drug Isis is developing and plans to
commercialize through its wholly owned subsidiary, Akcea
Therapeutics, to treat patients with familial chylomicronemia
syndrome and partial lipodystrophy; ISIS-TTRRx, a drug
Isis is developing with GSK to treat patients with the
polyneuropathy and cardiomyopathy forms of TTR amyloidosis; and
ISIS-SMNRx, a drug Isis is developing with Biogen to
treat infants and children with spinal muscular atrophy, a severe
and rare neuromuscular disease. Isis' patents provide strong
and extensive protection for its drugs and technology.
Additional information about Isis is available at
www.isispharm.com.
ISIS PHARMACEUTICALS' FORWARD-LOOKING STATEMENT
This
press release includes forward-looking statements regarding Isis'
strategic alliance with GSK, and the development, activity,
therapeutic and commercial potential and safety of
ISIS-TTRRx. Any statement describing Isis' 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. Isis' 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 Isis' forward-looking statements reflect
the good faith judgment of its management, these statements are
based only on facts and factors currently known by Isis. As a
result, you are cautioned not to rely on these forward-looking
statements. These and other risks concerning Isis' programs
are described in additional detail in Isis' annual report on Form
10-K for the year ended December 31,
2014, which is on file with the SEC. Copies of this
and other documents are available from the Company.
In this press release, unless the context requires otherwise,
"Isis," "Company," "we," "our," and "us" refers to Isis
Pharmaceuticals and its subsidiaries.
Isis Pharmaceuticals® is a registered trademark of
Isis Pharmaceuticals, Inc. Akcea Therapeutics™ is a trademark
of Isis Pharmaceuticals, Inc. KYNAMRO® is a
registered trademark of Genzyme Corporation.
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SOURCE Isis Pharmaceuticals, Inc.