Valneva/Emergent BioSolutions' Candidate Zika Vaccine Shows Early Clinical Promise
Executive Summary
A European/US company collaboration has reported encouraging safety and immunogenicity in early clinical studies with an alum-adjuvanted Zika vaccine based on inactivated whole virus.
A vaccine against Zika virus might have to be used in pregnant women during a Zika infection outbreak and so would need to be very safe and well-tolerated, one of the reasons why the CEO of the European vaccines company Valneva SE is encouraged by interim Phase I data involving its candidate Zika virus vaccine, VLA1601, being developed in collaboration with the US's Emergent BioSolutions Inc..
VLA1601 met the primary endpoint of the Phase I study, showing a favorable safety profile in all doses and schedules tested, the companies reported on Nov. 19. The companies are two of a number of firms attempting to develop a vaccine against the flavivirus, Zika virus, which has been associated with microcephaly in babies born to infected mothers, and Guillain-Barre syndrome (see sidebar).
The WHO has indicated that because of its potential use in pregnant women, a Zika vaccine based on inactivated virus might be more appropriate than other vaccine technologies, and Valneva has adapted its experience with the marketed inactivated Japanese encephalitis virus vaccine, Ixiaro, to the development of VLA1601 for Zika.
"The Zika virus is similar to the Japanese encephalitis virus, and Ixiaro uses an inactivated highly purified whole virus approach, so we were hopeful that VLA1601, based on the same alum-adjuvanted inactivated whole-virus technology, would have a good safety profile, and we saw that in terms of local and systemic tolerability," Valneva CEO Thomas Lingelbach told Scrip. Valneva and Emergent BioSolutions have also developed the Zika vaccine candidate without public funding, he added.
VLA1601 induced both dose- and schedule-dependent neutralizing antibodies against the Zika virus with kinetics similar to those associated with vaccines using the same technology. Seroconversion rates of up to 85.7% were seen 35 days post-immunization, and at interim analysis at day 56. "The seroconversion rate is not yet at the highest level, we would love to have 95%, and that would be the objective of a dose-finding Phase 2b study," Lingelbach noted.
The pathway for further development of VLA1601 has yet to be decided. Final results from the Phase I study, at day 208 after first vaccination, are expected in the first quarter of 2019, along with further immunogenicity data such as geometric mean titres.
At the end of Phase I, Emergent BioSolutions has opt-in rights to VLA1601 under an agreement signed in July 2017 which includes an opt-in milestone of $5.83m and further payments of up to $51m in development and commercial milestones and royalties to be paid to Valneva. (Also see "Deal Watch: GSK Declines Option As Ionis' Inotersen Nears Finish Line" - Scrip, 11 Aug, 2017.)
"We will have to decide whether Emergent will take it over, or to continue the joint development program, or something else, its yet to be decided, but both companies are encouraged and excited by the results," Lingelbach remarked.
With regard to the likely design of Phase III studies, Lingelbach noted that it was problematic to conduct gold-standard field efficacy trials versus placebo in diseases characterized by sudden outbreaks, but a "correlate of protection" acceptable to regulatory authorities might be the way forward.
Valneva is supporting an R&D pipeline, of various vaccine candidates, with a mix of product sales, research collaborations and the raising of additional capital; it reported product sales of €71.1m (+10% CER) in the first nine months of 2018, from the marketing of two travellers' vaccines, Ixiaro/Jespect and the enterotoxigenic Escherichia coli vaccine, Dukarol, and made a small operating profit of €900,000. Its net loss in the period totaled €3.3m. But in addition, Valneva also raised €50m from a private placement in September 2018, led by US healthcare investors, to support its R&D. (Also see "Finance Watch: With The Year's Biggest IPO, CFO Says Allogene Is Ready To Go 'Full Throttle'" - Scrip, 11 Oct, 2018.)
Products in its pipeline include a Lyme disease candidate vaccine, VLA15, which is expected to enter Phase II clinical studies at the end of 2018 and is believed to be the only such vaccine in clinical development, and a candidate Chikungunya vaccine, VLA1553, a potential one-shot vaccine, which is in Phase I studies; GlaxoSmithKline PLC has opt-in rights to the Lyme and Chikungunya vaccines after Phase II under a 2007 agreement.