A single injection of an experimental long-acting antiviral drug has demonstrated significant protection against influenza in a large-scale clinical trial, offering a potential new approach to flu prevention that doesn't rely on the immune system.
The drug, called CD388, reduced the risk of symptomatic flu infections by 76% at its highest dose in a Phase 3 trial involving 5,000 participants across the US and UK during the 2024 flu season, according to results from biotech company Cidara.
Novel Antiviral Approach Shows Promise
CD388 contains zanamivir, an FDA-approved antiviral drug effective against all flu strains that infect humans. However, while standard zanamivir is typically cleared from the body within hours, Cidara's researchers chemically modified the compound to persist in the body for months, where it can rapidly destroy invading flu viruses.
"It doesn't engage the immune system," said Jeffrey Stein, CEO of Cidara, highlighting a key distinction from traditional vaccines that rely on immune response activation.
The trial recruited participants aged 16 to 64 who were not at high risk for flu complications and had not yet received a flu vaccine that year. Researchers divided participants into four groups: three received single injections of CD388 at low, medium, or high doses, while the control group received a placebo.
Significant Reduction in Flu Infections
After approximately six months of follow-up, the results showed striking differences between treatment groups. While 33 people in the placebo group developed symptomatic flu infections, only eight participants who received the high dose of CD388 became ill with flu.
The medium and low-dose groups also showed substantial protection, with risk reductions of 61% and 58% respectively. "All doses demonstrated significant protection against influenza illness," said Nicole Davarpanah, chief medical officer at Cidara.
Side effects were similar across all groups, with injection site tenderness being the most common adverse reaction reported.
Advantages Over Current Vaccines
The approach offers several potential advantages over existing flu vaccines. Unlike seasonal vaccines, which require annual reformulation to match predicted circulating strains, CD388 would not need strain-matching and could be particularly valuable during "poor match" years when vaccine effectiveness drops significantly.
Current seasonal flu vaccines typically achieve around 60% effectiveness, but this can fall to as low as 10% when health authorities incorrectly predict the dominant strains for a given flu season.
"[Unlike vaccines, it] would not need to be matched to circulating strains and might be more effective in 'poor match' years or as part of pandemic preparedness should a novel influenza strain, such as H5N1 strains, move into humans," noted Penny Ward at King's College London.
Potential for Vulnerable Populations
The drug's mechanism of action could prove particularly beneficial for populations that typically respond poorly to vaccination, including older adults and immunocompromised individuals, since it doesn't rely on host immune response activation.
Based on prior data on zanamivir, flu strains are also unlikely to evolve resistance to the modified compound, according to Ward.
Cidara is planning additional trials to test CD388 in immunocompromised people aged 12 and above, a population that could particularly benefit from this approach.
Future Development Plans
Rather than replacing vaccines entirely, Stein suggests the drug may work best in combination with existing vaccination strategies, though this combination approach has not yet been tested in clinical trials.
The results come at a time of increasing vaccine hesitancy in some populations. "It avoids the controversy that is unfortunately now associated with vaccines," Stein noted.
The development represents a significant advance in flu prevention strategies, potentially offering a new tool for pandemic preparedness and protection of vulnerable populations who may not respond adequately to traditional vaccination approaches.
