CARLSBAD, Calif., Nov. 24, 2021 /PRNewswire/ -- Ionis
Pharmaceuticals, Inc. (NASDAQ: IONS) today announced that Pfizer
has provided an update on the Phase 2b study of vupanorsen, formerly
IONIS-ANGPTL3-LRx. Vupanorsen is an investigational
antisense therapy being developed for indications in cardiovascular
(CV) risk reduction and severe hypertriglyceridemia (SHTG). In the
dose-ranging study in subjects with elevated non-HDL-C and
triglycerides (TG), the study met its primary endpoint, achieving a
statistically significant reduction in non-HDL-C at all doses
tested at 24 weeks, compared to placebo. In addition, subjects
treated with vupanorsen achieved statistically significant
reductions in TG and ANGPTL3 at all dose levels at 24 weeks,
compared to placebo.
"We were pleased to see statistically significant reductions in
the primary endpoint, non-HDL-cholesterol, and in the secondary
endpoint of triglycerides at all doses tested. The topline results
of the Phase 2b study also showed
that vupanorsen dose-dependently lowered its target,
angiopoietin-like 3. Pfizer is continuing to review the findings to
determine next steps regarding future development. We look forward
to the full data set being presented at a medical meeting next
year," said Sotirios "Sam" Tsimikas, M.D., vice president of
global cardiovascular development and cardiovascular franchise lead
at Ionis.
The most common adverse events were injection site reactions,
which occurred most often in the highest vupanorsen dose group. The
most common laboratory abnormalities were increases in liver
enzymes, alanine aminotransferase (ALT) and aspartate
aminotransferase (AST) and were seen primarily at the higher doses.
There were no Hy's Law cases in vupanorsen-treated subjects, and no
meaningful changes in bilirubin. Certain doses of vupanorsen were
associated with increases from baseline in hepatic fat fraction,
measured by magnetic resonance imaging proton density fat fraction
at Week 24, compared to placebo. No subject had a confirmed
platelet count abnormality or a confirmed reduction in the
estimated glomerular filtration rate. There were no serious adverse
events (SAEs) related to treatment. The incidence of SAEs was
similar between active and placebo groups.
The global multicenter, double-blind, placebo-controlled,
dose-ranging Phase 2b study
TaRgeting ANGPTL3 with
an aNtiSense oLigonucleotide
in AdulTs with dyslipidEmia
(TRANSLATE-TIMI 70) enrolled 286 participants (≥ 40 years old) with
dyslipidemia, defined in this study as participants with elevated
non-HDL-C (≥ 100 mg/dL) and TG (150-500 mg/dL), who are receiving a
stable dose of a statin. Participants received either 80 mg, 120 mg
or 160 mg every 4 weeks, or 60 mg, 80 mg, 120 mg or 160 mg every
two weeks via subcutaneous injection. The study was designed to
assess the efficacy, safety, tolerability and pharmacokinetics of
vupanorsen, and the primary endpoint was percent change from
baseline in non-HDL-C at week 24.
About vupanorsen
Vupanorsen is an investigational antisense therapy discovered by
Ionis and being developed by Pfizer for potential indications in CV
risk reduction and SHTG. Vupanorsen is designed to reduce the
production of ANGPTL3 protein, a key regulator of triglyceride and
cholesterol metabolism, in the liver. This antisense therapy was
developed using Ionis' advanced LIgand Conjugated
Antisense (LICA) technology. The potential therapeutic
benefits of ANGPTL3 reduction are supported by the discovery that
people with a genetic deficiency in ANGPTL3 have reduced levels of
LDL-C and TG, and a decreased risk of diabetes and CV
disease.i In a Phase 1 study, subjects treated with
vupanorsen achieved robust, dose-dependent reductions in ANGPTL3,
TG, LDL-C, non-HDL-C and total cholesterol with a favorable safety
and tolerability profile.ii In a Phase 2a study,
vupanorsen met the primary endpoint of significant reductions in TG
levels and multiple secondary endpoints compared to placebo, with a
favorable safety and tolerability profile.iii
In November 2019, Pfizer licensed vupanorsen from Ionis in
a worldwide exclusive agreement.
About Ionis Pharmaceuticals, Inc.
For more than 30 years, Ionis has been the leader in
RNA-targeted therapy, pioneering new markets and changing the
standards of care with its novel antisense technology. Ionis
currently has three marketed medicines and a premier late-stage
pipeline highlighted by industry leading neurological and
cardiometabolic franchises. Our scientific innovation began and
continues with the knowledge that sick people depend on us, which
fuels our vision of becoming one of the most successful
biotechnology companies.
To learn more about Ionis visit www.ionispharma.com or
follow us on Twitter @ionispharma.
Ionis' Forward-looking Statement
This press release includes forward-looking statements regarding
Ionis' business, and the therapeutic and commercial potential of
vupanorsen and Ionis' technologies and 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, including those related
to the impact COVID-19 could have on our business, and including
those inherent in the process of discovering, developing and
commercializing medicines that are safe and effective for use as
human therapeutics, and in the endeavor of building a business
around such medicines. 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, 2020, and the most recent Form 10-Q
quarterly filing, 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.
References
i JAMA Cardiol. 2018 Oct
1;3(10):957-966.
ii N Engl J Med. 2017 Jul
20;377(3):222-232.
iii Eur Heart J. 2020 Oct 21;41(40):3936-3945.
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SOURCE Ionis Pharmaceuticals, Inc.