Today, the company reported positive 12-month antibody persistence data for VLA1553. That read-out follows the findings it released in March from its Phase 3 trial showing the investigational vaccine met all its primary and secondary endpoints.
With its vaccine potentially becoming the first chikungunya jab to receive approval in the US, Valneva’s VP and VLA1553 program director, Katrin Dubischar, shared key insights with us on the companys' Biologics License Application (BLA) submission process to the US Food and Drug Administration (FDA).
“The importance, particularly in the chikungunya indication, of determining the development strategy, of determining the BLA package contents - that, for us, was something that started very early in the process.”
Chikungunya is a sporadically occurring disease, she explained, and not one for which it is easy to develop a straightforward phase three clinical efficacy trial protocol. “Therefore, setting the strategy for this with the FDA was something we needed to do early on in development, and that, for me, was an integral part of the BLA process.”
In August, Valneva initiated rolling submission of its BLA to the FDA, seeking approval for VLA1553. It is on track to finalize that by the end of 2022. If the filing is accepted, the FDA will determine priority review eligibility along with the action due date upon which it will complete its evaluation. The VLA1553 program received FDA Fast Track and Breakthrough Therapy designations in 2018 and 2021, respectively. VLA1553 was also granted PRIority MEdicine (PRIME) designation by the EMA in 2020.
Valneva leveraged external support along the process, using specialized service providers but also undertaking academic collaborations to get access to world class knowledge, said Dubischar. “We have been partnering with the Coalition for Epidemic Preparedness Innovations (CEPI) as well.”
Recognizing the unmet medical need for chikungunya vaccines and the growing public health need that exists, CEPI has made chikungunya one of their target pathogens. “We also received a grant of more than US$20m from that organization, which helped us accelerate and advance the VLA1553 program, including in countries were the chikungunya virus is endemic."
Again, working through a partner, the company was able to get its clinical study in adolescents off the ground in Brazil.
In terms of its collaboration with academic institutes, Dubischar said that work was critical for establishing the studies required to help Valneva determine the surrogate endpoint. The company is seeking licensure of the vaccine based on a surrogate of protection agreed with the FDA that is reasonably likely to predict protection from chikungunya infection.
“In the case of the chikungunya vaccine, our approval pathway is a so-called accelerated approval pathway, by which the FDA can grant the licensure based on a surrogate marker.”
Valneva is eagerly waiting for the regulatory process to play out. “Usually, the FDA takes about two months after receiving a completed application to determine if it is accepting the filing or not. [If our file is accepted], we expect the review to continue throughout next year. We will, of course, work with the FDA during the entire review process.”
Clinical trial leapfrogging
When asked why she believes Valneva has been a forerunner in this space, Dubischar commented: “Our candidate is a live-attenuated vaccine. Given that particular feature, we were able to build certain design elements into our phase one study that allowed us to progress immediately into the phase three program, bypassing a phase two trial, which has really helped us accelerate its development.”
Looking at the key takeaways from the BLA process for other potential applicants, she said that holding repeated discussions with the regulators, alongside engaging often with experts in the field during the early planning stages is crucial, as it can help determine the correct pathway for the product.
In Valneva’s case, the company also found that the FDA was extremely appreciative of the fact that the vaccine candidate was addressing a significant unmet medical need; the drug’s priority designation enabled frequent interaction with the agency, she noted.
“The FDA shares our understanding that this is a potentially serious disease, and that it is, actually, a growing public health concern. It is a disease that is transmitted by mosquitoes, and, in the context of climate change, those mosquitoes are expanding their habitats."
The risk of the chikungunya virus spreading in the EU and the US is high. “This is something we believe needs to be taken very seriously. Therefore, we are eager to progress our vaccine candidate.”
Valneva currently plans to make additional regulatory submissions for VLA1553 in 2023. Meanwhile, the company has also moved to strengthen its management team, hiring Dipal Patel in November as its chief commercial officer. She is a recognized commercial industry leader, said Valneva, and can help the company to advance its chikungunya vaccine candidate towards potential market entry.
To make VLA1553 more accessible to Low and Middle Income Countries (LMIC), Valneva and Instituto Butantan in Brazil signed an agreement in January 2021 for the development, manufacturing and marketing of VLA1553. The collaboration falls within the framework of the agreement signed between CEPI and Valneva in July 2019.