The long wait for phase 3 data on Inovio Pharmaceuticals' COVID-19 vaccine just got longer. With DNA vaccine INO-4800 generating significantly lower antibodies against omicron than the original SARS-CoV-2, Inovio has paused enrollment and asked regulators to change the primary endpoint to prevention of severe disease.
Real-world data on authorized vaccines and a readout from a clinical trial of the Sanofi-GlaxoSmithKline jab show products designed to work against the original SARS-CoV-2 virus are less effective at preventing symptomatic infection with omicron. Having suffered setbacks including a 14-month clinical hold, Inovio is in the unenviable position of testing a vaccine against the ancestral virus in the omicron era.
Tests using clinical samples from individuals vaccinated with INO-4800 have eliminated lingering hopes that the vaccine triggers a stronger antibody response against omicron than authorized products, leaving Inovio facing the prospect of its candidate providing limited protection against symptomatic infection. In response, Inovio wants to switch its primary endpoint from symptomatic infection to severe disease.
“Omicron has thrown a curveball to all vaccine developers, with reduction in antibody responses from the original ancestral strain targeted vaccine,” Inovio CEO Joseph Kim, Ph.D., told investors on a quarterly result conference call. “We are taking a proactive step knowing that our probability of success in demonstrating prevention of severe disease with our vaccine against COVID-19 virus is high, and that’s the label that we would look for.”
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Kim’s confidence that INO-4800 can prevent severe disease is underpinned by in vitro evidence that the T-cell response is maintained against omicron. That mirrors the experience of other vaccines, which are no longer stopping almost all symptomatic infections but are still largely keeping people out of the hospital.
Inovio now plans to seek regulatory approval for the new endpoint. It is unclear how long that will take, with Kim sidestepping a direct analyst question about the timeline and only committing to completing the process “as expediently as possible.” The only certainty is that data from the trial will no longer land in the first half of 2022, as was previously expected.
The delay stems from a data safety monitoring board recommendation to pause enrollment while the informed consent form and investigator brochure are updated to reflect the potential impact of omicron. Participants who have already received their first dose can receive their second shot, and the pause isn’t related to safety. Kim said a “significant number” of participants have already been dosed.
One question for Inovio is whether its trial, which has a sample size of 7,000 to 10,000, is large enough to show a drop in severe COVID-19 in the vaccine arm. Severe COVID-19 is rare—Pfizer saw 31 cases at the six-month analysis of its 42,000-subject clinical trial—and omicron appears to be milder than early forms of the virus. Inovio has assessed the sample size, Kim said, and expects the original enrollment target to be sufficient.