Head-to-head data, presented at OPTIONS XII
for the Control of Influenza Conference, demonstrates
advantage of sa-mRNA over conventional mRNA in duration of immune
response; Results highlight CSL and Arcturus Therapeutics'
commitment to advancing COVID-19 vaccine innovation to protect
public health.
WALTHAM,
Mass. and SAN DIEGO,
Sept. 30,
2024 /PRNewswire/ -- Global biotechnology leader CSL
(ASX:CSL; USOTC:CSLLY) and self-amplifying messenger RNA (sa-mRNA)
pioneer Arcturus Therapeutics (Nasdaq: ARCT) today announced the
results of a head-to-head study demonstrating that self-amplifying
(sa-mRNA) COVID-19 vaccine maintained superior immunogenicity
compared to the conventional mRNA vaccine Comirnaty® for
up to one year against Wuhan-Hu-1, Omicron BA.4-5 and certain other
variants, and at one-sixth the dose of the comparator (5 μg vs
30 μg, respectively).
The data, presented as a poster at the OPTIONS XII for the
Control of Influenza conference, highlights 12-month follow-up
analysis of the Phase 3 trial conducted in Japan by Meiji Seika Pharma, evaluating a
booster dose of ARCT-154, showing that the vaccine elicited
superior immunogenicity and antibody persistence over
Comirnaty® for up to 12 months postvaccination, against
multiple SARS-CoV-2 strains and in both younger and older adult age
groups.
"The 12-month results from the ARCT-154 study continue to
establish the durability of immune response from this
self-amplifying mRNA vaccine and reinforce the ability of this
vaccine to provide protection against COVID-19 at lower doses
compared to conventional mRNA vaccines," said Jonathan Edelman, M.D., Senior Vice President,
Vaccines Innovation Unit, CSL. "We are proud to showcase at the
2024 OPTIONS conference with these important data about the first
sa-mRNA COVID-19 vaccine now approved in Japan."
Additional data presented by CSL and Arcturus finds that the
bivalent formula, ARCT-2301, developed on the same platform
as ARCT-154, induces superior immunogenicity over conventional
bivalent mRNA vaccine Comirnaty® that persists against
key variants up to six months postvaccination.
"The recent surge in COVID-19 infections and the emerging new
variants illustrate the critical need for vaccines that provide a
longer duration of protection compared to conventional mRNA
vaccines," said Igor Smolenov, M.D., Ph.D. Chief Development
Officer of Arcturus Therapeutics. "These compelling new studies
reaffirm that these sa-mRNA vaccines have the potential to offer
potent protection against COVID-19."
The COVID-19 vaccine from this sa-mRNA platform targeted against
the JN.1 variant is approved in Japan for immunization against COVID-19 in
adults 18 years and older and is being sold under the trade name
KOSTAIVE®.
ARCT-154 12-month Study Design and Results
The
randomized, double-blind, active-controlled Phase 3 study was
conducted at 11 clinical sites in Japan. The study enrolled
828 adults who had previously been fully immunized with three doses
of mRNA vaccine(s). Participants were randomized equally to receive
a booster dose of either ARCT-154 or Comirnaty®. Immune
responses were measured as neutralizing antibodies against the
Wuhan-Hu-1 and Omicron BA.4-5 strains in sera obtained at Day 1
before booster vaccination, and Days 29, 91, 181, and 361 after
vaccination of participants who were seronegative for SARS-CoV-2
nucleocapsid protein (N-protein), considered to be an indicator of
recent COVID-19 infection. At the same timepoints neutralizing
antibodies against Delta, Omicron BA.2, Omicron BA.2.86, and
Omicron XBB.1.5.6 variants were measured in subsets of participants
(~30 per group). Responses are expressed as group geometric mean
titers (GMT) with 95% confidence intervals, and geometric mean
titer ratio (GMTR) between the two vaccine groups at each
timepoint.
At Day 29, neutralizing antibodies (GMTs unadjusted) against the
Wuhan-Hu-1 strain in ARCT-154 recipients (n = 378) were superior to
those in the Comirnaty® group (n = 374): GMT = 5390 (95%
CI: 4899–5931) vs. 3738 (3442–4060), a GMT ratio of 1.44
(1.27–1.64). This advantage persisted through all time
points. At Day 361 (unadjusted) GMTs were 3396 (3019–3821)
and 1771 (1532–2047) in ARCT-154 (n = 272) and
Comirnaty® (n = 266) groups, a GMT ratio of 1.92
(1.59–2.31). Differences were also observed in responses against
Omicron BA.4-5, with GMT ratios of 1.31 (1.07–1.59) at Day 29 and
1.89 (1.42– 2.50) at Day 361. A subset of subjects who were
seronegative for N-protein displayed similar differences in immune
responses between ARCT-154 and Comirnaty® against
the Delta, Omicron BA.2, BA.2.86, and XBB.1.5.6 variants at Day
361. The GMT ratios were 1.88 (0.79–4.49) against Delta, 2.34
(1.06–5.17) against Omicron BA.2, 2.51 (1.00–6.31) against Omicron
BA.2.86 and 2.81 (1.09–7.28) against Omicron XBB.1.5.6.
Bivalent 6-month Study Design and Results
In this
randomized, multicenter, Phase 3, observer-blind, active-controlled
trial in Japan, fully-immunized
(3‒5 doses of mRNA vaccine) adults were randomized 1:1 to receive a
booster dose of ARCT-2301 or
Comirnaty® Original/BA.4-5. The primary objective
was to demonstrate non-inferiority of the immunogenicity of
ARCT-2301 vs. Comirnaty® Original/BA.4-5 at Day 29
as neutralizing antibody GMT and seroresponse rates (SRR) against
Omicron BA.4-5. Key secondary outcomes included titers of
neutralizing antibodies against Wuhan-Hu-1 and Omicron XBB.1.5.
Between September and November
2023, 930 men and women (19‒80 years) with at least three
prior mRNA COVID-19 vaccinations were enrolled at nine medical
centers in Japan and administered
ARCT-2301 (n = 465) or Comirnaty® Original/BA.4-5 (n =
465) boosters. At Day 29 ARCT-2301 (n = 398) induced superior
neutralizing antibody responses vs. Comirnaty® (n =
405) against Omicron BA.4-5 (GMT ratio 1•49 [95% CI: 1.26–1.76],
SRR difference 7.2% [95% CI: 0.6–13.7]), and against Wuhan-Hu-1
(GMT ratio 1.45 [1.28–1.63], SRR difference 12.5% [5.9–19.0]). The
difference persisted through six months with GMT ratios of 2.17
(95% CI: 1.75-2.69) and 1.98 (95% CI: 1.69-2.31), respectively.
Antibody responses against Omicron XBB.1.5 were also higher after
ARCT-2301 vs. Comirnaty® (GMT ratio 1.63
[1.36–1.94], SRR difference 16.7% [10.1–23.2]).
About sa-mRNA
mRNA vaccines help protect against
infectious diseases by providing a blueprint for cells in the body
to make a protein to help our immune systems recognize and fight
the disease. Unlike standard mRNA vaccines, self-amplifying mRNA
vaccines instruct the body to make more mRNA and protein to boost
the immune response.
About CSL
CSL (ASX:CSL; USOTC:CSLLY) is a global biotechnology company with a
dynamic portfolio of lifesaving medicines, including those that
treat hemophilia and immune deficiencies, vaccines to prevent
influenza, and therapies in iron deficiency and nephrology. Since
our start in 1916, we have been driven by our promise to save lives
using the latest technologies. Today, CSL – including our three
businesses: CSL Behring, CSL Seqirus and CSL Vifor – provides
lifesaving products to patients in more than 100 countries and
employs 32,000 people. Our unique combination of commercial
strength, R&D focus and operational excellence enables us to
identify, develop and deliver innovations so our patients can live
life to the fullest. For inspiring stories about the promise of
biotechnology, visit CSLBehring.com/Vita and follow us
on Twitter.com/CSL. For more information about CSL,
visit www.CSL.com.
About Arcturus
Founded in 2013 and based in San
Diego, California, Arcturus
Therapeutics Holdings Inc. (Nasdaq: ARCT) is a global mRNA
medicines and vaccines company with enabling technologies: (i)
LUNAR® lipid-mediated delivery, (ii) STARR® mRNA Technology
(sa-mRNA) and (iii) mRNA drug substance along with drug product
manufacturing expertise. Arcturus developed
KOSTAIVE®, the first self-amplifying messenger
RNA (sa-mRNA) COVID vaccine in the world to be approved. Arcturus
has an ongoing global collaboration for innovative mRNA vaccines
with CSL Seqirus, and a joint venture in Japan, ARCALIS,
focused on the manufacture of mRNA vaccines and therapeutics.
Arcturus' pipeline includes RNA therapeutic candidates to
potentially treat ornithine transcarbamylase (OTC) deficiency and
cystic fibrosis (CF), along with its partnered mRNA vaccine
programs for SARS-CoV-2 (COVID-19) and influenza. Arcturus'
versatile RNA therapeutics platforms can be applied toward multiple
types of nucleic acid medicines including messenger RNA, small
interfering RNA, circular RNA, antisense RNA, self-amplifying RNA,
DNA, and gene editing therapeutics. Arcturus' technologies are
covered by its extensive patent portfolio (over 400 patents and
patent applications in the
U.S., Europe, Japan, China, and other countries).
For more information, visit www.ArcturusRx.com. In addition,
please connect with us on Twitter and LinkedIn.
Forward-Looking Statements
This press release contains
forward-looking statements that involve substantial risks and
uncertainties for purposes of the safe harbor provided by the
Private Securities Litigation Reform Act of 1995. Any statements,
other than statements of historical fact included in this press
release, are forward-looking statements, including those regarding
strategy, future operations, the likelihood that KOSTAIVE will
provide a longer duration of protection, the likelihood and timing
of future approvals of KOSTAIVE anywhere in the world including
Europe, the plans to submit
additional regulatory filings and timing thereof, that preclinical
or clinical data will be predictive of future clinical results, and
the impact of general business and economic conditions. Arcturus
may not actually achieve the plans, carry out the intentions or
meet the expectations or projections disclosed in any
forward-looking statements such as the foregoing and you should not
place undue reliance on such forward-looking statements. These
statements are only current predictions or expectations, and are
subject to known and unknown risks, uncertainties, and other
factors that may cause our or our industry's actual results, levels
of activity, performance or achievements to be materially different
from those anticipated by the forward-looking statements, including
those discussed under the heading "Risk Factors" in Arcturus' most
recent Annual Report on Form 10-K, and in subsequent filings with,
or submissions to, the SEC, which are available on the SEC's
website at www.sec.gov. Except as otherwise required by law,
Arcturus disclaims any intention or obligation to update or revise
any forward-looking statements, which speak only as of the date
they were made, whether as a result of new information, future
events or circumstances or otherwise.
CSL Media Contacts:
Sue
Thorn
Mobile: 617 799 3151
Email: sue.thorn@cslbehring.com
Australia:
Jimmy Baker
Mobile: +61 450 909 211
Email: Jimmy.Baker@csl.com.au
Asia
Pacific:
Hamish
Walsh
+61 422 424 338
Email: hamish.walsh@seqirus.com
Arcturus Media Contact:
Neda
Safarzadeh
VP, Head of IR/PR/Marketing
Email: IR@arcturusrx.com
View original content to download
multimedia:https://www.prnewswire.com/news-releases/self-amplifying-mrna-covid-19-vaccine-demonstrates-superior-immune-response-compared-with-mrna-vaccine-at-12-months-post-vaccination-302262465.html
SOURCE CSL