The US Department of Health and Human Services (HHS) announced major funding support for two new flu treatments—a new type of antiviral targeted for hospitalized patients and a monoclonal antibody.
If the drugs advance through clinical trials and are approved, they would break new ground in the battle against influenza. The new antiviral would give doctors a strong tool that can be given during a wider treatment window than current medications, and the monoclonal antibody would be the first of its kind for treating flu.
Funded through the HHS Assistant Secretary for Preparedness and Response (ASPR), the initial support for both drugs is worth $132.6 million over the next several years, with possible extensions bringing the total to $335.5 million.
First in a new antiviral class
Yesterday HHS announced a contract for advanced development for the experimental drug JNJ-872, in a new class of antivirals. Early studies suggest the drug can yield clinical benefits even when given much later than 48 hours after symptoms begin.
Neuraminidase inhibitors like oseltamivir (Tamiflu) and zanamivir (Relenza) are often used for patients hospitalized for flu, but they are typically more effective when given within 48 hours.
Robin Robinson, PhD, director of ASPR's Biomedical Advanced Research and Development Authority (BARDA), said in an HHS statement that patients aren't typically hospitalized for flu within 48 hours of developing symptoms, so effective treatment options are needed later in the illness course. "This is a critical health priority as tens of thousands of flu patients are hospitalized each year in the United States, and that number can be even higher in a pandemic."
Formerly called VX-787, the drug was developed by Boston-based Vertex Pharmaceuticals, which licensed it in June 2014 to Janssen Pharmaceuticals, a division of Johnson & Johnson. The drug is an azaindole inhibitor of the cap-snatching function of the PB2 subunit of the influenza A virus polymerase complex.
HHS said the drug has a different mechanism of action compared with current flu medications, and that having drugs with unique mechanisms of action may be important for antiviral-resistant strains, especially when potential pandemic strains emerge. The agency added that its support for the drug is also based on possible use in people at high risk for flu complications, such as older people, children, and those with underlying medical conditions.
In its announcement, HHS said the contract will provide up to $103.5 million for late-stage clinical development over the next 51 months, with an option for additional work that would total about $131 million. Funding is designed to cover phase 3 studies in high-risk and hospitalized populations and final development of a validated commercial-scale manufacturing process.
BARDA will provide technical assistance and consult with Janssen to explore a new approach for manufacturing JNJ-872 for possible use in the company's future products. Called "continuous manufacturing," the process eases interruptions at multiple production states, enabling a continuous flow of materials throughout the process.
"We're interested in manufacturing innovation as part of medical countermeasure development to be as agile, efficient, and cost-effective as possible, and continuous manufacturing has that potential," Robinson said.
Monoclonal antibody treatment
Today HHS announced a contract to help support an experimental monoclonal antibody treatment for flu (VIS410) developed by Visterra, Inc., based in Cambridge, Mass. Monoclonal antibodies bind to parts of flu viruses that are common to a wide range of strains, neutralizing them and reducing the body's viral load. HHS added that the treatment's flu virus target evolves more slowly than those of other drugs, which could make VIS410 a useful tool in managing antiviral-resistant strains.
Robinson said in a statement today that having multiple antiviral treatment options is important not only in pandemic settings, but also for seasonal flu. "Developing antiviral drugs that work against many strains of influenza provides a cost-efficient way to boost pandemic preparedness and at the same time potentially alleviate the suffering of hundreds of thousands of people who are hospitalized with influenza every year," he said.
HHS said the initial $29.1 million, 40-month contract will cover safety and efficacy trials, manufacturing of materials for clinical studies, and manufacturing optimization. It said preclinical studies have suggested that the treatment is more effective than current antivirals and is likely to be safe and effective in patients with flu risk factors.
The agency added that, under the contract, studies will also explore if the treatment has benefits when given more than 48 hours after symptom onset.
BARDA's contract with Visterra could be extended for up to 5 years for a total of $204.5 million, which would clear the way for larger trials in severely ill and hospitalized flu patients, including children.
Last month researchers published promising preclinical results showing that the treatment protected mice against H3N2 and H7N9 flu viruses. The Proceedings of the National Academy of Sciences (PNAS) study also suggested a synergistic effect with oseltamivir.
The company said in an Aug 18 press release that the findings support continued development of VIS410 as a single-administration treatment for seasonal and pandemic flu.
In general, monoclonal antibody treatment is costly, because the production process is more complicated, and high doses are sometimes needed.
Sep 28 HHS press release
Sep 29 HHS press release
Jun 19, 2014, CIDRAP News scan "Maker of candidate flu drug enters licensing agreement"
Aug 18 Visterra press release
Aug 17 PNAS abstract