A Novel Influenza Antiviral in Development Could Offer Months of Illness Prevention

Antiviral Fc conjugates (AVCs) could be the future of influenza prevention and treatment, offering months of protection and taking the guesswork out of the seasonal flu vaccine.

More than 155 million people in the United States received a seasonal flu vaccine during the 2017-2018 flu season. During that season, the US Centers for Disease Control and Prevention (CDC) estimates that 48.8 million people experienced flu illness, leading to 959,000 hospitalizations and 79,400 deaths. Although the flu vaccine is the best way to prevent flu illness, the vaccine was just 36% effective overall during the 2017-2018 season.

As research continues into the development of more effective flu vaccines, Cidara Therapeutics recently presented data on its Cloudbreak immunotherapy platform candidate for an influenza antiviral, offering a new approach to preventing and treating flu illness. According to the company, it has developed a single molecule that offers a potent, long-acting, and bi-specific biologic designed to target and destroy influenza virus while also directing and enhancing the immune response at the site of infection. The approach straddles the preventive effects of flu vaccination along with an antiviral medication’s capability to treat flu illness.

In an interview with Contagion^® Cidara Therapeutic's senior vice president of research, Les Tari, PhD, said that the company is advancing to preclinical development candidates this quarter after starting the influenza program in July. “With molecules like this, we’re not looking to replace vaccines, which play a critical role in public health,” said Tari. “What we know is that vaccine efficacy is far from excellent, especially in the elderly and very young. Our vision is that one to two subcutaneous doses of our AVCs could prevent influenza in humans for an entire flu season, with or without concomitant vaccine administration—and cover strains that are missed by the vaccine in any given year. And since our AVCs possess potent intrinsic antiviral activity even in the absence of immune engagement, we can also protect patient populations with compromised immune systems, where vaccines don’t perform well.”

Although antiviral medications such as Tamiflu have a 48-hour window of treatment following onset of symptoms, Cidara says their novel AVCs showed significant protection in mice out to 72 hours post-infection and have been effective against influenza viruses resistant to Tamiflu. “Our antiviral agents are engineered carefully to target specific, highly conserved regions on the pathogen that are difficult to mutate without a major fitness cost,” explained Tari. “By adding the synergistic immune mediated killing mechanism to the action of the antiviral, we see enhanced activity, which should also minimize the probability of developing resistance. Additional benefits of this strategy are improved potency of the antiviral due to the multivalent presentation on the Fc, and a dramatic improvement in half-life compared to conventional small molecule approaches.”

Cidara’s data is promising so far and shows that AVCs exhibit potent activity against both seasonal and pandemic strains of influenza, as well as highly potent in vitro and in vivo activity, but Tari emphasizes that the company will conduct several years of rigorous development before AVCs become mainstream and make a public impact. “Taken together, we believe our AVCs have the potential to become a critical part of the global fight against influenza, both in prevention and treatment,” he concluded.