CARLSBAD, Calif., Nov. 3, 2015 /PRNewswire/ -- Isis
Pharmaceuticals, Inc. (NASDAQ: ISIS) announced today positive
preliminary results from an ongoing investigator sponsored,
open-label Phase 2 study in patients with TTR amyloid
cardiomyopathy, which included patients with familial amyloid
cardiomyopathy (FAC) and patients with wild-type transthyretin
amyloidosis (wt-TTR amyloidosis, previously referred to as senile
systemic amyloidosis, or SSA). In this study, patients receive one
injection of ISIS-TTRRx once a week. The study will
continue for 24 months. Data from patients treated for 12 months
were presented today (abstract # PM14) by the lead investigator,
Merrill D. Benson, M.D., at the
First European Congress on Hereditary ATTR amyloidosis in
Paris, France. Isis will
review these data and the overall development plan for
ISIS-TTRRx in a webcast scheduled for Tuesday, Nov. 3 at 8:00
a.m. Eastern Time.
"Data from our study is encouraging. The study is designed to
monitor progression of cardiomyopathy in patients treated with
ISIS-TTRRx. The MRI data measured left ventricular mass
for the first three patients to complete 12 months on therapy.
These data show evidence of disease stabilization when compared to
baseline. These observations compare favorably to those from our
previously published natural history data. In the natural history
study1, using the same measurements, we observed disease
progression at 12 months," said Merrill D.
Benson, M.D., professor of pathology and lab medicine,
medical and molecular genetics at Indiana
University School of Medicine. "Our previously reported
echocardiographic measurements in these patients also showed
disease stabilization after six months of ISIS-TTRRx
treatment. The MRI data from longer term treatment I reported today
support our earlier observations."
- Patients in Dr. Benson's previously published natural history
study with an interventricular septum thickness (IVS) >1.3cm
(mean =1.9) at study entry had a mean increase of 14
percent in left ventricular mass as measured by MRI at 12
months.
- Patients entering the Phase 2 ISIS-TTRRx study had
baseline IVS > 1.3cm (mean =2.03). The first three patients
treated with ISIS-TTRRx had a mean
decrease of 1.9 percent in left ventricular mass from
baseline as measured by MRI at 12 months.
- No discontinuations and injection site reactions occurring in
less than two percent of all injections, which were predominantly
mild. The safety and tolerability profile of ISIS-TTRRx
supports continued development.
Isis Pharmaceuticals also announced new data from the ongoing
open-label extension (OLE) study of ISIS-TTRRx in
patients with familial amyloid polyneuropathy (FAP) who have
completed the Phase 3 study. An analysis conducted on the first 38
patients to reach at least three months of treatment in the OLE
study showed a maximum reduction in TTR protein levels of up to 92
percent with a mean maximum (nadir) reduction of 76 percent as
compared to patients' baseline TTR levels at entry into the Phase 3
study. Patients continue to be enrolled in the OLE as they complete
the Phase 3 study. In addition, a blinded analysis of the Phase 3
study showed injection site reactions occurring in approximately
one percent of all injections, which were predominantly mild. The
Phase 3 study is expected to complete enrollment by the end of the
year.
"We are encouraged by the substantial reductions in TTR protein
we have observed in patients who have a variety of variants of the
TTR gene. We believe that the observed tolerability profile and the
convenience of dosing ISIS-TTRRx (one low volume, (1.5
mL) once weekly, subcutaneous injection that enables at home
administration) contribute significantly to the high rate of
patient retention in our Phase 3 FAP study and the high (100
percent) rate of eligible patients enrolling in the OLE study,"
said Brett Monia, senior vice
president of drug discovery and franchise leader for oncology and
rare diseases at Isis Pharmaceuticals. "The substantial reduction
in TTR protein together with our tolerability profile suggests that
ISIS-TTRRx has the potential to be an attractive
treatment for all forms of TTR amyloidosis."
In a poster presented today titled, 'A phase 3 clinical trial
with ISIS-TTRRx, a 2nd-generation antisense
oligonucleotide targeting transthyretin (TTR), for the treatment of
TTR amyloid cardiomyopathy' (abstract # PM15), GSK provided an
overview on the design of the ISIS-TTRRx Phase 3 study
in patients with TTR amyloid cardiomyopathy (CARDIO-TTR). This
randomized, double-blind, international, multi-center study will
evaluate the efficacy and safety of ISIS-TTRRx in
approximately 500 TTR amyloid cardiomyopathy patients diagnosed
with either FAC or wt-TTR amyloidosis. The primary endpoint will be
based on clinical composite outcomes that will include mortality,
cardiac transplant and cardiovascular hospitalization.
"We are committed to a broad development program for
ISIS-TTRRx to treat all patients who suffer from TTR
amyloidosis," said Sarah Boyce,
chief business officer at Isis Pharmaceuticals. "This is
highlighted by GSK's substantial investment in CARDIO-TTR, which
includes both FAC and wt-TTR amyloidosis patients and an additional
small Phase 3 FAP study to support regulatory filings in
Asia. We are encouraged by the
evolving product profile of ISIS-TTRRx across all
forms of TTR amyloidosis as one patient–friendly, once weekly
injection, and we believe it has the potential to be the
first-in-class and best-in-class RNA-targeted drug. GSK is
the right partner for ISIS-TTRRx. They have the
resources to support patient diagnosis and access with a global
sales effort and operations in over 100 countries. GSK plans
to develop ISIS-TTRRx for TTR amyloidosis patients
worldwide."
ABOUT 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 single 300 mg injection, once weekly, at home
self-administered low-volume subcutaneous injection and is designed
to inhibit the production of all forms of TTR protein, including
both hereditary and wild-type, offering a unique approach to treat
all types of TTR amyloidosis. ISIS-TTRRx has already
demonstrated sustained and robust TTR reductions in multiple
clinical studies in multiple indications of TTR-related
amyloidosis.
ISIS-TTRRx is currently being evaluated in a Phase 3
randomized, double-blind, placebo-controlled, international study
in patients with FAP. The study is 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.
ABOUT TTR AMYLOIDOSIS
TTR amyloidosis is a fatal
genetic disease in which patients 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. There are an
estimated 10,000 FAP patients worldwide.
Patients with FAC experience ongoing debilitating heart damage
resulting in progressive heart failure. Therapeutic options
for the treatment of FAC are very limited and there are currently
no drugs approved for the treatment of FAC. There are an
estimated 40,000 FAC patients worldwide.
wt-TTR amyloidosis (previously referred to as senile systemic
amyloidosis or SSA) is a form of TTR amyloidosis associated with
the aging process and is characterized by deposition of amyloid
fibrils derived from normal or wild-type TTR protein.
Although the hereditary forms of TTR are more likely to
misfold and aggregate in various tissues, the normal or wild-type
TTR protein can also cause heart damage. Amyloid deposition
is mainly seen in the myocardium, resulting in arrhythmia (atrial
fibrillation) and/or heart failure. wt-TTR amyloidosis
typically affects male patients over 80 years, but is also
indicated in younger patients, with an onset around 50 years.
There are an estimated 200,000 patients worldwide.
Webcast
At 8:00 a.m. Eastern
Time, Nov. 3, 2015, Isis will
conduct a webcast to discuss the latest data and overall
development plan for ISIS-TTRRx. A live audio
webcast of the presentation will be available on the "Investor
& Media" section of the Company's website,
www.isispharm.com. Interested parties may listen to the call
by dialing 877-443-5662. A replay will be available for a
limited time. The slides presented on the webcast will be
available on Isis' website at www.isispharm.com at the time of the
webcast and for a limited time after.
ABOUT ISIS PHARMACEUTICALS, INC.
Isis 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, Isis has created a
large pipeline of first-in-class or best-in-class drugs, with over
a dozen drugs in mid- to late-stage development. Drugs
currently in Phase 3 development include volanesorsen, a drug Isis
is developing and plans to commercialize through its wholly owned
subsidiary, Akcea Therapeutics, to treat patients with familial
chylomicronemia syndrome and familial partial lipodystrophy;
ISIS-TTRRx, a drug Isis is developing with GSK to treat
patients with all forms of TTR amyloidosis; and
ISIS-SMNRx, a drug Isis is developing with Biogen to
treat infants and children with spinal muscular atrophy.
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
Pharmaceuticals' strategic alliance with GSK, and the development,
activity, therapeutic and commercial potential and safety of
ISIS-TTRRx to treat all forms of TTR amyloidosis. 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, 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,
"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.
1Benson MD et al. Am J Cardiol. 2011 Jul
15;108(2):285-9.
Logo -
http://photos.prnewswire.com/prnh/20130807/LA60006LOGO
To view the original version on PR Newswire,
visit:http://www.prnewswire.com/news-releases/isis-pharmaceuticals-reports-an-update-on-isis-ttr-rx-including-positive-data-from-multiple-clinical-studies-presented-today-at-the-ec-attr-meeting-300170825.html
SOURCE Isis Pharmaceuticals, Inc.