Non-Vaccine Seasonal Flu Preventive Shows Promise in Phase 2b Clinical Trial: Cidara Therapeutics

Cidara Therapeutics' investigational long-acting antiviral CD388 achieved statistically significant prevention efficacy (PE) against symptomatic influenza in adults aged 18 to 64 years, according to topline results of the company's phase 2b NAVIGATE trial. The randomized, double-blind, placebo-controlled study enrolled more than 5,000 healthy unvaccinated adults who were randomly assigned to receive single doses of CD388 of 450 mg, 300 mg, and 150 mg at the beginning of the influenza season.

_{©Kateryna_Kon/stock.adobe.com}

Researchers observed statistically significant PE across the 3 doses over 24 weeks compared to placebo, the company said in a statement, satisfying the NAVIGATE study's primary endpoint:

450 mg: 76.1% PE vs placebo (P < .001)

300 mg: 61.3% PE (P = .002)

150 mg: 57.7% PE (P = .005)

Placebo: 2.8% influenza-like illness (ILI) incidence.

PE was also statistically significant for a group that combined the 2 higher dose groups at 68.6% (P < .001).

The study also met investigators' secondary endpoints using fever thresholds lower than that used for the primary endpoint. NAVIGATE confirmed the drug's efficacy at the CDC-defined threshold of 37.8°C or greater and at 37.2°C or greater, with PE maintained through 28 weeks at statistically significant levels.

"Results such as these are unprecedented in influenza and support our confidence in the potential of CD388 to offer robust, once-per-season protection against influenza A and B," said Jeffrey Stein, Ph.D., president and chief executive officer of Cidara. "As a long-acting antiviral drug, CD388 was designed to provide once per season protection against all strains of influenza in all people, irrespective of immune status."

Researchers defined the primary endpoint as protocol-defined influenza-like illness (ILI), which required central laboratory-confirmed RT-PCR positive influenza infection via nasopharyngeal swab, new onset fever (oral temperature ≥38.0°C), and new onset of at least two respiratory symptoms or one respiratory symptom plus one systemic symptom.

Secondary endpoints using lower fever thresholds confirmed the drug's efficacy. At the CDC-defined threshold of ≥37.8°C, prevention efficacy reached 76.1%, 55.3%, and 54.7% for the 450mg, 300mg, and 150mg groups respectively. At ≥37.2°C, efficacy measured 71.1%, 49.6%, and 46.5% for the corresponding dose groups. All secondary endpoints achieved statistical significance, and efficacy persisted through 28 weeks.

CD388 was well tolerated, according to Cidara, with no drug-related adverse events reported across dosing arms. The safety profile, including occurrence of injection site reactions, was described as similar to placebo.

"Results such as these are unprecedented in influenza and support our confidence in the potential of CD388 to offer robust, once-per-season protection against influenza A and B...irrespective of immune status," Jeffrey Stein, PhD, president and chief executive officer of Cidara, said in the statement.

CD388 is a novel drug-Fc conjugate (DFC) comprising multiple copies of a neuraminidase inhibitor conjugated to a proprietary Fc fragment of a human antibody. Unlike vaccines or monoclonal antibodies, the low molecular weight biologic functions as a long-acting small molecule inhibitor. CD388 is designed to provide universal protection against seasonal and pandemic influenza strains regardless of immune status. A single intramuscular or subcutaneous injection is anticipated to provide season-long protection against infection. DFC activity is not reliant on an immune response and so efficacy is expected regardless of immune status, the company said.

Cidara announced groundwork data for the NAVIGATE trial in March 2023, with promising efficacy and safety data from a planned interim analysis of a phase 2a trial evaluating the pre-exposure prophylactic activity of CD388 against the H3N2 influenza A virus strain, according to a news release at the time. Although the sample was small (n = 56), half receiving a single dose of CD388 150 mg and half placebo, Cidara reported a decrease in viral replication in the upper respiratory tract and in influenza infection in those treated with the study drug. There were no safety or tolerability signals reported. The phase 2a data established preliminary clinical proof of concept for the ongoing CD388 development program.

The company has submitted an end of phase 2 meeting request to the FDA to discuss the phase 2b results and design of the phase 3 development program. Cidara plans to present additional results from the NAVIGATE trial at upcoming scientific conferences in 2025.

References

1. Cidara Therapeutics announces positive topline results from its phase 2b NAVIGATE tiral evaluating CD388, a non-vaccine preventative of seasonal influenza. Cidara Therapeutics. News release. June 23, 2025. Accessed June 30, 2025. https://www.globenewswire.com/news-release/2025/06/23/3103267/0/en/Cidara-Therapeutics-Announces-Positive-Topline-Results-from-its-Phase-2b-NAVIGATE-Trial-Evaluating-CD388-a-Non-Vaccine-Preventative-of-Seasonal-Influenza.html

2. Cidara Therapeutics announces promising interim phase 2a data assessing the safety and efficacy of a single dose of CD388 in an influenza challenge model. News release. Cidara Therapeutics. March 1, 2023. Accessed June 30, 2025. https://www.cidara.com/news/cidara-therapeutics-announces-promising-interim-phase-2a-data-assessing-the-safety-and-efficacy-of-a-single-dose-of-cd388-in-an-influenza-challenge-model/\