New COVID-19 sa-mRNA Results from CSL and Arcturus Therapeutics Demonstrate Longer Duration of Immunity Compared to Conventional COVID-19 mRNA Vaccine Booster

Rhea-AI Summary

CSL and Arcturus Therapeutics announce positive results of a Phase 3 study evaluating a booster dose of ARCT-154, the world's first approved self-amplifying messenger RNA (sa-mRNA) COVID-19 vaccine, compared to a conventional mRNA COVID-19 vaccine. The study conducted in Japan demonstrates Immunological Non-Inferiority to Wuhan Strain and Superior Immunogenicity to Omicron BA.4/5 Variant. The new analysis at 6 months post-vaccination shows that ARCT-154 induces a longer immune response compared to Comirnaty for both the original Wuhan strain and Omicron BA.4/5 variant, and an advantage in antibody persistence. The results follow the approval of the world's first sa-mRNA COVID-19 vaccine for adults by Japan Ministry of Health, Labor and Welfare in November 2023.

Positive

• Positive results of the study demonstrate Immunological Non-Inferiority to Wuhan Strain and Superior Immunogenicity to Omicron BA.4/5 Variant compared to the conventional mRNA COVID-19 vaccine.
• ARCT-154 induces a longer immune response compared to Comirnaty for both the original Wuhan strain and Omicron BA.4/5 variant, and an advantage in antibody persistence.
• The study follows the approval of the world's first sa-mRNA COVID-19 vaccine for adults by Japan Ministry of Health, Labor and Welfare in November 2023.

Negative

• None.

Medical Research Analyst

The recent findings from the Phase 3 study comparing ARCT-154, a self-amplifying mRNA (sa-mRNA) vaccine, with the conventional mRNA vaccine, Comirnaty®, are significant in the context of public health and vaccine development. The study's data indicate that ARCT-154 elicits a longer-lasting immune response at a lower dose, which could have substantial implications for vaccine distribution logistics and cost-effectiveness. The geometric mean titers (GMTs), a measure of the concentration of antibodies, were consistently higher for ARCT-154 recipients over the six-month period, suggesting a more durable immune response.

This extended duration of immunity could reduce the frequency of booster vaccinations needed, potentially easing the burden on healthcare systems and improving global vaccination coverage. Furthermore, the lower dosage requirement of ARCT-154 could alleviate supply chain constraints and enable more efficient use of resources. The implications for stakeholders include potential shifts in vaccine procurement strategies and the need to update immunization guidelines to integrate new vaccine technologies.

Economist

From an economic perspective, the introduction of a more potent and longer-lasting vaccine like ARCT-154 may influence the competitive landscape of pharmaceutical companies involved in COVID-19 vaccine production. The market demand could pivot towards vaccines that offer longer protection and require lower dosages, affecting sales and market shares of existing vaccine producers. For CSL and Arcturus Therapeutics, the successful development and approval of ARCT-154 could translate into significant market opportunities and a stronger bargaining position in supply agreements with governments and international health organizations.

In the long run, the adoption of sa-mRNA technology could lead to cost savings for healthcare systems due to decreased needs for frequent booster campaigns. However, it is essential to monitor the market's reaction to new entrants and the potential for price adjustments across the vaccine portfolio. The financial performance of companies investing in sa-mRNA technology will be closely watched by investors, as the market assesses the scalability and profitability of this innovation.

Market Research Analyst

The market's reception of ARCT-154 will depend on several factors, including regulatory approvals in other regions beyond Japan, the effectiveness of the vaccine against future variants and the ability of CSL and Arcturus Therapeutics to scale production. The reported data suggest a competitive advantage for ARCT-154, but market penetration will hinge on clinical outcomes, cost and the agility of the companies to respond to evolving market needs.

Stakeholders should consider the potential for ARCT-154 to disrupt the current vaccine market, taking into account the ongoing evolution of the virus and public health policies. The ability of the sa-mRNA vaccine to maintain higher GMTs against both the Wuhan strain and the Omicron variant is a crucial factor that may influence future vaccine choices by individuals and healthcare providers. Additionally, the stock market may react to these developments, as positive clinical outcomes typically bolster investor confidence in biotech firms.

Study conducted by Meiji Seika Pharma in Japan

• Short communication follows previously published data in The Lancet Infectious Diseases demonstrating Immunological Non-Inferiority to Wuhan Strain and Superior Immunogenicity to Omicron BA.4/5 Variant Compared to First-Generation mRNA Vaccine Booster 
• New data demonstrates continuous advantage of sa-mRNA over conventional mRNA vaccine in terms of duration of immune response
• These results follow approval of the world's first sa-mRNA COVID-19 vaccine for adults by Japan Ministry of Health, Labor and Welfare in November 2023

KING OF PRUSSIA, Pa. and SAN DIEGO, Feb. 5, 2024 /PRNewswire/ -- Global biotechnology leader CSL (ASX:CSL; USOTC:CSLLY) and Arcturus Therapeutics (Nasdaq: ARCT) today announced the results of a follow-up analysis of a Phase 3 study evaluating a booster dose of ARCT-154 , the world's first approved self-amplifying messenger RNA (sa-mRNA) COVID-19 vaccine, compared to a conventional mRNA COVID-19 vaccine. ARCT-154 was administered at one-sixth the dose of Comirnaty^® (5 μg vs 30 μg, respectively).

The new analysis at 6 months post-vaccination shows that ARCT-154 induces a longer immune response as compared to Comirnaty for both the original Wuhan strain and Omicron BA.4/5 variant and an advantage in antibody persistence.

"These results further support sa-mRNA's differentiating attribute to provide prolonged protection against COVID-19 at lower doses," said Jonathan Edelman, M.D., Senior Vice President, Vaccines Innovation Unit, CSL. "Protecting the global public from viral respiratory diseases remains a top priority for us, and we look forward to continuing to collect and share data at the twelve-month post-booster mark."

"This data, coupled with the initial Phase 3 results and approval in Japan late last year, show that this innovative vaccine technology has the potential to provide significant advancements over conventional mRNA vaccines including prolonged protection at lower doses," said Pad Chivukula, Ph.D., Chief Scientific Officer of Arcturus Therapeutics.

ARCT-154 Six-Month Data Report
This randomized, double-blind, active-controlled study, conducted at 11 sites in Japan assessed the immunogenicity of ARCT-154 and Comirnaty^® at one, three- and six-months post-booster. Participants who displayed seropositivity for SARS-CoV-2 N-protein on Days 1, 29, 91 or 181 were considered indicative of recent COVID-19 infection and therefore, were progressively excluded from the analysis, leaving 332 and 313 participants in ARCT-154 and Comirnaty^® groups, respectively, eligible for inclusion at the six-month immunogenicity evaluation.

At baseline, participants in both groups had similar geometric mean titers (GMTs) surrogate virus neutralizing antibodies against Wuhan-Hu-1 strain  (GMT ratio was 0.94 (95% CI 0.78-1.13)). One-month post-booster, the ARCT-154 group displayed a higher immune response with GMT of 5390 (95% CI 4899-5931, n = 378) compared to Comirnaty^® group with GMT of 3738 (95% CI 3442-4060, n = 367), and a GMT ratio of 1.44 (95% CI 1.27–1.64).

Three months post-booster GMTs were 5928 (95% CI 5414–6491, n = 369) and 2899 (2648–3175, n = 356), with a higher GMT ratio of 2•04 (1•80–2•32). Day 91 titers were equal to or greater than Day 29 titers in 205 of 369 (55•6% [95% CI 50•3–60•7]) ARCT-154 recipients, but in only 108 of 356 (30•3% [25•6–35•4]) Comirnaty^® recipients. Due to different rates of antibody waning, by Day 181 GMTs were 4119 (95% CI 3723–4557, n = 332) and 1861 (1667–2078, n= 313) in ARCT-154 and Comirnaty^® groups, respectively, maintaining a GMT ratio of 2•21 (1•91–2•57) between vaccine groups. GMTs against Wuhan-Hu-1 remained numerically higher 180 days after ARCT-154 than those observed 28 days after the Comirnaty^® booster.

The same pattern of superior immunogenicity and slower decline in Omicron BA.4/5 neutralizing antibodies was observed: GMTs were comparable at baseline (GMT ratio of 0.94 (95% CI 0.71-1.26), and increased to 2125 (95% CI 1841–2453) vs. 1624 (1418–1858) at Day 29 after ARCT-154 and Comirnaty^®, then waned to 1892 (1646–2175) and 888 (764–1031), respectively, at Day 91. Between Days 29 and 91 titers were stable or increased in 128 of 369 (34•7% [95% CI 29•8–39•8]) ARCT-154 recipients, compared with 36 of 356 (10.1% [7•2–13•7]) in the Comirnaty^® group. The difference in neutralizing activity against Omicron BA.4/5 was maintained to Day 181 when GMTs were 1119 (95% CI 960–1305) and 495 (413–595), with a GMT ratio of 2•26 (1•78–2•86) in favor of ARCT-154.

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. Different from 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 Therapeutics
Founded in 2013 and based in San Diego, California, Arcturus Therapeutics Holdings Inc. (Nasdaq: ARCT) is a global late-stage clinical 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 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 deficiency and cystic fibrosis, 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 issued 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.

About Meiji Seika Pharma Co., Ltd.
Meiji Seika Pharma, since it launched penicillin in 1946, has been providing efficacious and high-quality pharmaceutical products such as therapeutics and vaccines for infectious diseases, therapeutics for central nervous system diseases as well as generic drugs in response to various medical needs. As a leading company in the field of infectious diseases, we are strengthening our platform for infection control and prevention with vaccines and antimicrobial agents.

Arcturus 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 plans to collect and share additional data and analyses and the potential of the sa-mRNA technology to provide advancements over conventional mRNA vaccines. 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, 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.

Media Contacts:

CSL Media Contacts:
Sue Thorn
Mobile: 617 799 3151
Email: sue.thorn@cslbehring.com

Australia:
Kim O'Donohue
Mobile: 0449 884 603
Email: kim.odonohue@csl.com.au

Jimmy Baker
Mobile: +61 450 909 211
Email: Jimmy.Baker@csl.com.au

Arcturus Media Contact:
Neda Safarzadeh
VP, Head of IR/PR/Marketing
Email: IR@arcturusrx.com

 

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SOURCE CSL

What are the results of the Phase 3 study conducted by CSL and Arcturus Therapeutics?

The study demonstrates Immunological Non-Inferiority to Wuhan Strain and Superior Immunogenicity to Omicron BA.4/5 Variant compared to the conventional mRNA COVID-19 vaccine. It shows that ARCT-154 induces a longer immune response compared to Comirnaty for both the original Wuhan strain and Omicron BA.4/5 variant, and an advantage in antibody persistence.

What is the ticker symbol for CSL?

The ticker symbol for CSL is CSLLY.

When was the world's first sa-mRNA COVID-19 vaccine approved for adults?

The world's first sa-mRNA COVID-19 vaccine for adults was approved by Japan Ministry of Health, Labor and Welfare in November 2023.

What are the key findings of the study in Japan regarding ARCT-154?

The study shows that ARCT-154 induces a longer immune response compared to Comirnaty for both the original Wuhan strain and Omicron BA.4/5 variant, and an advantage in antibody persistence.