Bavarian Nordic's Chikungunya Vaccine Succeeds in Phase 3, Building Support for BLA

After posting disappointing news related to its RSV vaccine, Bavarian Nordic rebounded with positive results from its phase 3 trial of its chikungunya vaccine candidate, CHIKV VLP.

The investigational virus-like particle-based chikungunya virus vaccine met all co-primary end points in a double-blind, placebo controlled clinical trial (NCT05072080) in 3254 adults and adolescents age 12 to 64 years.

The mosquito-born disease is historically tied to occurrences in Africa and Asia; however, outbreaks of the virus have cropped up in more than 110 countries across Asia, Africa, Europe, and the Americas since the early 2000s. The spread of the virus has been perpetuated by viral adaptations that make it more easily carried by Aedes albopictus mosquitoes, also known as Asian tiger mosquitoes, as well as increased international trade and travel. Misdiagnosis is common since symptoms overlap with those seen in dengue and Zika viruses. Affected individuals typically experience sudden-onset fever and debilitating joint pain--some of which can last months to years after infection.

“We are highly encouraged by the positive topline results now demonstrated in both Phase 3 studies of our chikungunya vaccine candidate. Our focus remains to finalize the studies and prepare for regulatory submissions next year,” said Paul Chaplin, president and CEO of Bavarian Nordic, in a statement. “With a fast and durable response, our vaccine has the potential to be the best in class to prevent chikungunya infections in adolescents to elderly adults. Chikungunya that can often result in a severe and incapacitating disease affects large parts of the world, and with international travel on the rise again, our CHIKV vaccine offers a significant opportunity to address this large unmet medical need.”

In the trial, participants were randomly assigned to receive a single intramuscular injection of CHIKV VLP or placebo. At up to 22 days post-injection, the vaccine was shown to be highly immunogenic in health adults and adolescents. A strong induction of chikungunya neutralizing antibodies in 98% of vaccines in the active group were observed, which were greater than or equal to antibody titres agreed upon by authorities as a marker of seroprotection.

Significant neutralizing antibodies were observed in 97% of participants at 2 weeks, with 86% of the subjects maintaining seroprotective-levels of the neutralizing antibodies at 6 months. Overall, the vaccine was well tolerated with mild to moderate adverse events.

The company previously disclosed additional topline data from another phase 3 study (NCT05349617), in healthy older adults (at least 65 years old). Results showed that the vaccine induced neutralizing antibodies in 87% of vaccines 22 days after injection.

The results of the late-stage trials will be used to support a biologics license application in the US as well as a marketing authorization application with the European Medicines Agency in 2024. The company hopes to make the vaccine available in 2025.

The news is a boon to Bavarian Nordic, who posted disappointing results from its phase 3 clinical trial of MVA-BN RSV, its late-stage vaccine candidate in the increasingly crowded RSV pipeline. The randomized, double-blind, placebo-controlled trial enrolled more than 20,000 older adults at least 60 years of age. The data showed that the vaccine had a 59% efficacy in preventing at least 2 lower respiratory tract disease (LRTD) symptoms; however, it only showed a 42% efficacy in symptoms of more severe LRTD, missing the co-primary end points.

Based on this, the company has decided to discontinue its RSV program. That makes for 1 less player in the RSV space, which currently has 2 vaccines approved for older adults from Pfizer and GSK, and a pending FDA approval for a pediatric indication for Pfizer's maternal vaccine.

Competition isn't only steep in RSV, though. Bavarian Nordic's chikungunya vaccine is a few steps behind another investigational vaccine from Valneva, who published phase 3 trial results of its vaccine candidate, VLA1553, back in June in The Lancet. Those trial results are supporting a BLA that is already under priority review by the FDA with a PDUFA date sometime later this month, setting it up to be potentially the first licensed vaccine to address this unmet need.

In the phase 3 trial that included 4128 participants, a single vaccination of VLA1553 induced seroprotective chikungunya virus neutralizing antibody levels in 98.9% of participants within 28 days, irrespective of age, with sustained antibodies through 180 days post-vaccination. With an overall safe profile, the results "position VLA1553 as an excellent candidate for the prevention of chikungunya," the study authors concluded.