CARLSBAD, Calif. and
CAMBRIDGE, Mass., March 6, 2017 /PRNewswire/ -- Akcea
Therapeutics, a wholly owned subsidiary of Ionis Pharmaceuticals,
Inc. (NASDAQ: IONS), today announced that the pivotal Phase 3
APPROACH study of volanesorsen met its primary endpoint of reducing
triglyceride levels in patients with familial chylomicronemia
syndrome (FCS).
APPROACH is a randomized, double-blind, placebo-controlled,
52-week Phase 3 study in 66 patients with FCS, a rare disease
affecting approximately 3,000 to 5,000 patients worldwide. The
average incoming triglyceride level of patients in the study was
2,209 mg/dL. Patients treated with volanesorsen experienced
robust reductions in triglycerides and related benefits as
follows:
- For the primary endpoint of the study, volanesorsen-treated
patients (n=33) achieved a statistically significant (p<0.0001)
mean reduction in triglycerides of 77% from baseline after 3 months
of treatment, compared to a mean increase of 18% in placebo-treated
patients (n=33). This represented a mean absolute reduction
of 1,712 mg/dL in treated patients.
- The treatment effect observed was sustained over the 52-week
treatment period.
- 50% of the treated patients who entered the study with
triglycerides ≥750 mg/dL achieved triglyceride levels less than 500
mg/dL after 3 months of treatment. By comparison, none of the
placebo-treated patients achieved this level (p<0.003).
- Volanesorsen-treated patients with the highest documented
frequency of pancreatitis attacks suffered no attacks during the
52-week treatment period (p=0.02).
- A reduction in abdominal pain was observed in
volanesorsen-treated patients compared to placebo-treated
patients.
"We are excited about the strong profile of volanesorsen in not
only robustly reducing triglycerides, but also providing additional
important patient benefits. FCS is a life-threatening, rare
disease with multiple severe daily and chronic manifestations. We
believe the efficacy and safety data from volanesorsen studies
demonstrate a favorable risk-benefit profile for patients with
FCS," said Paula Soteropoulos,
president and chief executive officer, Akcea
Therapeutics.
The APPROACH study will support the regulatory submission for
FCS of volanesorsen. Additional data from the study will be
presented at an upcoming medical meeting.
"People with FCS have inherited mutations that inhibit the
activity of lipoprotein lipase, the enzyme required to break down
triglycerides carried by chylomicrons. The results from this
study provide encouraging data about triglyceride reduction in
patients with FCS treated with volanesorsen, and are consistent
with data from other clinical trials with the drug. Since
there are currently very few effective treatment options for FCS
patients, I am encouraged that, if approved, volanesorsen could
offer FCS patients an option to achieve the therapeutic benefit
they need," said Daniel Gaudet, M.D.
Ph.D., head of the Clinical Lipidology and Rare Lipid Disorders
Unit, Community Gene Medicine Center, Department of Medicine,
Université de Montreal.
The APPROACH results were consistent with findings from both the
Phase 3 COMPASS study as well as the Phase 2 program for
volanesorsen. In the COMPASS study, the five FCS patients
treated for three months with volanesorsen experienced a 73%
average decrease in triglycerides, which represented a mean
absolute reduction of 1,511 mg/dL. In the Phase 2 program, which
was the subject of two separate publications in the New England
Journal of Medicine, the three FCS patients profiled in one
publication had an average triglyceride reduction after three
months of treatment with volanesorsen of 69% or a mean absolute
reduction of 1,298 mg/dL.
"The success of APPROACH represents an important milestone
towards our first regulatory submissions for volanesorsen in the
U.S., Europe and Canada in 2017," said Dr. Louis O'Dea, chief medical officer, Akcea
Therapeutics. "We seek to bring this new treatment as
expeditiously as possible to FCS patients who have a high unmet
need with potentially life-threatening consequences."
In the study, there were no treatment-related liver adverse
events, including no increases in liver fat. There were no
treatment-related renal adverse events. The most common
adverse event in the volanesorsen-treated group of patients was
injection site reactions (ISRs), which were mostly mild. Five
volanesorsen-treated patients discontinued due to ISRs.
Declines in platelet counts associated with decreases in
triglycerides were observed in many patients. These were generally
well managed with dose adjustment. Five volanesorsen-treated
patients discontinued due to declines in platelets. No patients
discontinued in the last six months of the study after platelet
monitoring was fully implemented. In the volanesorsen Phase 3
program, there were infrequent serious platelet events (grade 4
thrombocytopenia) in three volanesorsen-treated patients, which
resolved without incident following cessation of dosing. In
the entire volanesorsen clinical program 232 individuals have been
treated with volanesorsen, including 66 FCS patients, some for more
than two years.
WEBCAST INFORMATION
Interested parties may listen to the call by dialing 877-443-5662
or access the webcast at www.ionispharma.com. Webcast replay will
be available for a limited time at the same address.
ABOUT VOLANESORSEN, FCS and FPL
Volanesorsen is an
antisense drug in development for two rare metabolic disorders: FCS
and familial partial lipodystrophy (FPL). Volanesorsen is
designed to reduce the production of ApoC-III, a protein produced
in the liver that plays a central role in the regulation of plasma
triglycerides and may also affect other metabolic parameters.
FCS is a severe, rare genetic disorder characterized by
extremely high levels of triglycerides and the risk of recurrent,
potentially fatal pancreatitis. People with FCS are unable to
effectively clear large, triglyceride-rich lipid particles called
chylomicrons due to a deficiency of lipoprotein lipase, an enzyme
that helps to break down triglycerides. There is no effective
therapy available. Additional information on FCS is available
at www.fcsfocus.com and through the FCS Foundation at
http://www.livingwithfcs.org and the LPLD Alliance at
www.lpldalliance.org.
FPL is a severe, rare genetic metabolic disorder characterized
by an inability of the body to store fat in normal locations.
This results in high levels of triglycerides in the bloodstream,
abnormal fat distribution around and within organs, such as the
liver and heart, and a range of metabolic abnormalities, including
severe insulin resistance. People with FPL are at increased
risk of acute pancreatitis in addition to other long-term,
progressive manifestations, such as premature cardiomyopathy,
atherosclerosis, and liver disease. Additional information on
FPL is available through Lipodystrophy United at
www.lipodystrophyunited.org.
For more information about this clinical trial program for
volanesorsen, please visit www.apociii.com.
ABOUT VOLANESORSEN CLINICAL PROGRAM
The volanesorsen
clinical program is focused on generating data to support
registration in two severe, rare, genetic diseases, FCS and
FPL. The program is supported by Phase 1 and Phase 2 studies
that explored volanesorsen doses across both healthy volunteers and
a number of patient populations, including patients with
hypertriglyceridemia, Type 2 diabetes, and FCS. In these
studies, volanesorsen resulted in dose‑dependent, consistent and
sustained reductions in plasma ApoC‑III and in triglyceride levels,
both as a single agent and as an add‑on to fibrates. Akcea
and Ionis have now successfully completed two Phase 3 studies,
APPROACH and COMPASS, which support planned regulatory filings for
the treatment of FCS. Patients with FCS who have completed or
meet the study criteria for the APPROACH study can enroll in an
open-label extension study. Akcea and Ionis are also
currently conducting, BROADEN, a Phase 3 study in patients with
FPL.
ABOUT AKCEA THERAPEUTICS
Akcea Therapeutics is a
development and commercialization company focused on transforming
the lives of patients with serious cardiometabolic lipid
disorders. Akcea has a robust portfolio of development-stage
drugs covering multiple targets and diseases using advanced
RNA-targeted antisense therapeutics. Akcea's most advanced
drug, volanesorsen, is being developed to address two severe, rare,
genetically defined lipid disorders, FCS and FPL. Based on
positive results in the Phase 3 program, Akcea is preparing
regulatory dossiers for volanesorsen for the treatment of FCS and
conducting a Phase 3 study evaluating volanesorsen in patients with
FPL. Akcea's drug pipeline includes three additional novel
antisense drugs designed to address a number of lipid risk factors,
including ApoC-III, triglycerides, Lp(a), and
LDL-cholesterol. Akcea is continuing to assemble the global
infrastructure to develop and commercialize the drugs in its
pipeline. Akcea is a wholly owned subsidiary of Ionis
Pharmaceuticals, Inc. and is located 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 and/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 Ionis
is developing and, if approved, plans to commercialize through its
wholly owned subsidiary, Akcea Therapeutics, to treat patients with
FCS and FPL; IONIS-TTRRx, a drug Ionis is developing
with GSK to treat patients with all forms of TTR amyloidosis; and
SPINRAZATM (nusinersen), a drug Ionis is developing with
Biogen to treat infants and children with spinal muscular
atrophy. Ionis' patents provide strong and extensive
protection for its drugs and technology. Additional
information about Ionis is available at www.ionispharma.com.
FORWARD-LOOKING STATEMENT
This press release includes
forward-looking statements regarding the business of Ionis
Pharmaceuticals, Inc. and Akcea Therapeutics, Inc., a subsidiary of
Ionis Pharmaceuticals, and the therapeutic and commercial potential
of volanesorsen and other products in development. Any
statement describing the companies' 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. The companies' 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 the companies' forward-looking
statements reflect the good faith judgment of its management, these
statements are based only on facts and factors currently known by
the companies. As a result, you are cautioned not to rely on
these forward-looking statements. These and other risks
concerning the companies' programs are described in additional
detail in Ionis Pharmaceuticals, Inc.'s annual report on Form 10-K
for the year ended December 31, 2016,
which is on file with the SEC. Copies of this and other
documents are available at www.ionispharma.com.
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 Pharmaceuticals™ is a trademark of Ionis Pharmaceuticals,
Inc. Akcea Therapeutics™ is a trademark of Ionis
Pharmaceuticals, Inc. SPINRAZATM is a trademark of
Biogen.
To view the original version on PR Newswire,
visit:http://www.prnewswire.com/news-releases/akcea-and-ionis-announce-positive-results-from-pivotal-study-of-volanesorsen-in-patients-with-familial-chylomicronemia-syndrome-fcs-300418191.html
SOURCE Ionis Pharmaceuticals, Inc.