CSL's ARCT-154: The World’s First Self-Amplifying mRNA Vaccine Approved for COVID-19 in Adults

A patient receiving a COVID-19 vaccine.

(Adobe Stock 639765475 by Talia Mdlungu/peopleimages.com)

Despite the appearance of the public emergency waning, the battle against COVID-19 persists. An integral aspect of this ongoing struggle involves the tireless global pursuit of novel vaccines. The quest for innovative and effective vaccine candidates remains crucial in fortifying our defenses against the virus, adapting to emerging variants, and achieving comprehensive immunity in the face of the pandemic’s evolving challenges. This commitment to exploring new vaccine possibilities underscores the collective determination to safeguard communities worldwide and mitigate the long-term impact of the COVID-19 threat.

Answering questions from Infection Control Today^® (ICT^®) about the groundbreaking approval of ARCT-154, the world's first self-amplifying mRNA (sa-mRNA) COVID-19 vaccine by Japan's Ministry of Health, Jonathan Edelman, MD, Senior VP of CSL's Vaccines Innovation Unit, discusses this historic milestone. Edelman elaborates on the vaccine's significance, clinical findings, collaboration with Meiji Seika Pharma, and how sa-mRNA technology addresses challenges, ushering in a new era for vaccine platforms.

ICT: Can you elaborate on the significance of Japan's Ministry of Health, Labour and Welfare granting approval for ARCT-154, the self-amplifying mRNA (sa-mRNA) COVID-19 vaccine, and how it reflects CSL's commitment to global public health?

Jonathan Edelman, MD: This approval in Japan is a historic milestone for CSL, as it marks the world’s first self-amplifying mRNA vaccine approved for COVID-19 in adults. The milestone underscores CSL’s promise to develop and deliver innovations where there is a public health need. The approval also expands CSL’s comprehensive portfolio of innovative vaccines that combat respiratory viral diseases and is the first sa-mRNA vaccine.

ICT: With ARCT-154 being the first sa-mRNA vaccine in the world to be registered, how does this milestone contribute to the evolution of mRNA vaccine technology and its potential impact on protecting against COVID-19 and other infectious diseases?

JE: We believe the technology behind our novel, self-amplifying messenger RNA vaccine, ARCT-154, has the potential to create more potent cellular immune responses with increased duration of protection, all with lower doses of mRNA.

ICT: The approval is based on positive clinical data, including studies conducted in Vietnam and a Phase 3 COVID-19 booster trial. Could you share key findings from these studies and how they demonstrate the efficacy and safety profile of ARCT-154 compared to standard mRNA COVID-19 vaccines?

JE: The efficacy of ARCT-154 was established in a Phase 1,2,3 study conducted in Vietnam during the height of the Delta wave of the pandemic, showing 95% protection against severe disease, including death, and 55% protection against all infections, published on MedRxiv and under peer review currently.

The Phase 3 booster study published in The Lancet Infectious Diseases found that ARCT-154 produced a higher (noninferior) immune response after 4 weeks against the original Wuhan-Hu-1 virus and, importantly, a superior immune response against the Omicron BA4/5 variant of COVID-19 compared to the standard mRNA vaccine Comirnaty. [This was a double-blind, multicenter, randomized, controlled, phase 3, non-inferiority trial.]

ICT: CSL Seqirus partnered exclusively with Meiji Seika Pharma to distribute ARCT-154 in Japan. How does this collaboration strengthen CSL's position in providing innovative vaccines for respiratory viral diseases, especially in the ongoing global efforts to combat COVID-19?

JE: Collaborating with Meiji Seika Pharma provides a partner with the infrastructure in Japan to market and distribute our self-amplifying mRNA COVID-19 vaccine and will mark CSL’s entry into the COVID-19 vaccine market with differentiated, self-amplifying mRNA technology.

ICT: The sa-mRNA technology used in ARCT-154 can potentially create more potent cellular immune responses and increase the duration of protection. Could you discuss how this innovation addresses key challenges in vaccine development and administration and what implications it may have for future vaccine platforms and strategies?

JE: One challenge with the original mRNA vaccines for COVID-19 is that their protection seems to wane within 6 months of administration, requiring frequent revaccination. A second challenge is that they have limited ability to protect against emerging variants until the vaccine is updated to that new variant. We believe sa-mRNA technology found in ARCT-154 can address both of these limitations by providing protection that lasts up to 1 year from vaccination and offering a broader range of coverage for variants of concern as evidenced by the Japan booster study and other data presented at the recent mRNA meeting in Berlin last year.