CARLSBAD, Calif.,
April 24, 2018
/PRNewswire/ -- Ionis Pharmaceuticals, Inc. (NASDAQ: IONS),
the leader in antisense therapeutics, today presented top-line data
from the Phase 1/2 study of IONIS-HTTRx (RG6042) in
people with early stage Huntington's disease (HD) at the
70th American Academy of Neurology (AAN) meeting in
Los Angeles, California. Results
from exploratory analyses of data from the study demonstrated
correlations between reductions in mutant huntingtin (mHTT), the
disease-causing protein, and improvements in clinical measures of
Huntington's disease.
HD is a rare, progressive, neurodegenerative disease
caused by genetic mutation in the huntingtin gene, resulting in the
production of mHTT protein, which gradually destroys neurons in the
brain and results in deterioration in mental ability and physical
control. Ionis designed IONIS-HTTRx (RG6042), a
Generation 2+ antisense drug, to specifically reduce the production
of the huntingtin protein, including mHTT.
"Since the discovery of the gene that causes Huntington's
disease 25 years ago, we've been working to discover a drug that
targets the cause of the disease—the mutant huntingtin protein.
With the results from the Phase 1/2 study with
IONIS-HTTRx, we have cleared the first major hurdle in
developing such a drug. The substantial lowering of the mutant
huntingtin protein, combined with additional data from exploratory
clinical measures presented today and the good safety profile we
observed in the study, give us hope that this new drug may have the
potential to slow, or perhaps halt, the progression of this
devastating disease," said Dr. Sarah
Tabrizi, professor of clinical neurology, director of the
University College London's Huntington's Disease Centre and the
global lead investigator on the study. "The next step is to advance
the drug into a larger study designed to demonstrate the potential
clinical benefit of reducing the toxic mutant huntingtin protein in
people with Huntington's disease."
Phase 1/2 Study
Results:
- Significant, dose-dependent reductions in mHTT were
observed in CSF of treated participants with mHTT reductions of up
to approximately 60% and mean reductions of approximately 40% in
CSF observed at the two highest doses, 90 mg (p<0.01) and 120 mg
(p<0.01).
-
- A 40% to 60% reduction in CSF corresponds to an estimated
55% to 85% reduction in mHTT in the cortex and 20% to 50% in the
caudate regions of the brain in humans, based on a predictive model
developed from data collected in rodents and non-human
primates.
- mHTT levels were continuing to decline at the last
measurement time in the study with further decreases in mHTT
anticipated; based on modelling and clinical results, maximum
reduction predicted at approximately six months after first
dose.
- No serious adverse events were reported in treated
participants and most adverse events (AEs) were mild and considered
unrelated to study drug. No participants discontinued from the
study.
Exploratory Clinical Outcome Results:
- In an exploratory post-hoc analysis, the degree of mHTT
lowering was correlated with improved scores at three months in
several clinical measures commonly used in Huntington's disease
clinical studies.
-
- Total Motor Score (TMS): rho=0.39 (p=0.007)
- Symbol Digit Modalities Test (SDMT): rho=-0.30
(p=0.044)
- Stroop Word Reading Test (SWRT): rho=0.08
(p=0.60)
- Total Functional Capacity (TFC) score: rho=-0.27
(p=0.066)
- In addition, a significant correlation was observed with
the degree of mHTT lowering and the Composite Unified Huntington's
Disease Rating Scale (cUHDRS) score at Day 85 (rho=-0.41,
p=0.004).
"These important clinical results further demonstrate that
targeting the reduction of the toxic mutant huntingtin protein with
IONIS-HTTRx has the potential to be disease-modifying,"
added Dr. C. Frank Bennett, senior
vice president of research and franchise leader for the
neurological programs at Ionis Pharmaceuticals. "Following SPINRAZA
for the treatment of patients with spinal muscular atrophy, this is
our second antisense drug to show good target engagement in the
CNS. These drugs, along with the two others we have in clinical
studies and the five we have in preclinical development further
validate the broad potential of our antisense technology to treat
patients with neurological diseases."
About the Phase 1/2 Study
The study was a randomized, placebo-controlled
dose escalation study in 46 people with early
stage Huntington's disease. Study participants were treated for 13
weeks with four intrathecal injections of 10 mg, 30 mg, 60 mg, 90
mg or 120 mg of IONIS-HTTRx (RG6042) or placebo (3:1
active to placebo), administered monthly. The study's primary
objective was to evaluate the safety and tolerability of
IONIS-HTTRx (RG6042). The study was also designed to
measure the effect of IONIS-HTTRx (RG6042) on levels of
the mutant huntingtin protein in the cerebral spinal fluid (CSF).
Exploratory analyses included several clinical measures commonly
used in Huntington's disease studies.
An open-label extension (OLE) study for patients who
participated in the Phase 1/2 study is ongoing.
Ionis' partner, Roche, exercised its option to license
IONIS-HTTRx following the completion of a Phase 1/2
study and is responsible for all development and commercial
activities. Planning is already underway for Roche to advance
IONIS-HTTRx (RG6042) to a pivotal study to demonstrate
the clinical efficacy and safety of
IONIS-HTTRx.
About Huntington's Disease (HD)
Huntington's Disease (HD) is a rare, genetic, progressive,
neurodegenerative disease resulting in deterioration in mental
abilities and physical control. In the U.S., there are
approximately 30,000 individuals (one in 10,000) with symptomatic
HD and more than 200,000 people at risk of having inherited HD. HD
is referred to as a triplet repeat disorder and is one of a large
family of genetic diseases in which certain gene sequences are
mistakenly repeated. In HD, the trinucleotide sequence in the gene
that encodes for the HTT protein is repeated more than 36 times.
The resulting mHTT protein is toxic and gradually damages neurons
in the brain. Symptoms of HD usually appear between the ages of 30
to 50 years and continually worsen over a 15- to 20-year period.
Ultimately, the weakened individual succumbs to pneumonia, heart
failure or other complications. Presently, there is no effective
disease-modifying treatment for HD, and current products focus only
on managing disease symptoms.
About IONIS-HTTRx (RG6042)
IONIS-HTTRx (RG6042) is an antisense drug
designed to reduce the production of all forms of the huntingtin
protein (HTT), including its mutated variant, mHTT, which is the
driver of HD. IONIS-HTTRx
(RG6042) offers a unique approach to treat all
patients with HD, irrespective of their individual HTT mutation.
IONIS-HTTRx (RG6042) has been granted orphan drug
designation by the U.S. Food and Drug Administration (FDA) and
by the European Medicines Agency (EMA) for the treatment
of patients with HD.
About Ionis/Roche Collaboration
Roche and Ionis are collaborating to develop antisense
drugs to treat HD. The alliance combines Ionis' antisense expertise
with Roche's knowledge and experience in clinical development of
anti-neurodegenerative therapeutics. In December 2017, Roche licensed
IONIS-HTTRx from Ionis for $45
million and has renamed the investigational molecule
RG6042. In total, Ionis has generated $100 million in up-front, milestone and license
payments and is eligible to receive an additional $335 million in milestone payments as
IONIS-HTTRx (RG6042) progresses in development and
regulatory approval. If commercialized, Ionis is
eligible to receive tiered double-digit royalties up to the
mid-teens on sales of IONIS-HTTRx
(RG6042). Roche is responsible for all
IONIS-HTTRx (RG6042) development, regulatory and
commercialization activities and costs.
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. Inotersen and
volanesorsen are two antisense drugs that Ionis discovered and
successfully advanced through Phase 3 studies. Inotersen is
under regulatory review for marketing approval in the U.S. and EU
for the treatment of patients with hereditary ATTR amyloidosis.
Volanesorsen 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. Volanesorsen is also in a Phase 3 study in patients with
familial partial lipodystrophy, or FPL. Akcea, an affiliate of
Ionis focused on developing and commercializing drugs to treat
patients with serious and rare diseases, will commercialize
inotersen and volanesorsen, if approved. 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 Ionis' alliance with Roche and the development, activity,
therapeutic potential, commercial potential and safety of
IONIS-HTTRx (RG6042). 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, 2017,
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, "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 Akcea Therapeutics, Inc. SPINRAZA® is a registered
trademark of Biogen.
View original content with
multimedia:http://www.prnewswire.com/news-releases/new-data-from-ionis-htt-rx-phase-12-study-demonstrates-correlation-between-reduction-of-disease-causing-protein-and-improvement-in-clinical-measures-of-huntingtons-disease-300634883.html
SOURCE Ionis Pharmaceuticals, Inc.