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Objective 3: Therapeutics – deployment, early availability, and novel development

BARDA Pandemic Influenza Preparedness and Response Strategy

Current Preparedness Activities

The influenza therapeutics program is focused on filling the gaps in treatment across the spectrum of influenza infection. While the Strategic National Stockpile has a significant quantity of influenza antivirals, which are anticipated to be effective against pandemic influenza, there are limitations in utility and benefit of those products.  Currently, there are no FDA-approved treatments for hospitalized patients with influenza and approved antivirals have shown to be ineffective at treating patients very late in the disease course. To address this gap, BARDA is investing in therapeutics for the treatment of acute respiratory distress syndrome (ARDS), including ARDS caused by influenza infections. 

Specifically, BARDA is planning a Phase 2 platform clinical trial investigating three host-directed therapeutics for the treatment of ARDS. In late 2023, BARDA partnered with PPD, a Fisher Lifesciences Company, to conduct the platform trial and the first patients are expected to be randomized into the study in 2024. In addition to collecting safety and efficacy data on enrolled patients, biomarker data investigating the natural history of this heterogeneous disease will be collected. The biomarker data should aid in the planning of a pivotal phase 3 clinical study by identifying specific patients that may benefit from a specific therapeutic or therapeutic mechanism of action.


Future Research Priorities

Another gap in the spectrum of available therapeutics for influenza is pre-exposure prophylaxis (PrEP). There are four antivirals approved for the treatment of influenza, with three also approved for post-exposure prophylaxis (PEP) of influenza and two with PrEP indications (oseltamivir and zanamivir). Oseltamivir and zanamivir must be dosed every day to achieve PrEP, which creates patient compliance issues as well as being logistically challenging to provide enough antivirals for PrEP in an influenza pandemic. 

BARDA is planning to invest in up to 10 PrEP therapeutic candidates that require one dose to provide six months of protection, which is the entire influenza season (minimum requirement is one month of protection for a single dose). The end goal is to provide an FDA-licensed therapeutic for PrEP to protect healthcare workers and first responders in the event of an influenza pandemic with a novel virus. These populations may be highly exposed to pandemic influenza patients, and a PrEP therapeutic can be a bridge until a well-matched pandemic influenza vaccine becomes available. In addition, there is a likely seasonal market for a PrEP therapeutic that could be used in combination with seasonal influenza vaccines to protect the most vulnerable patient populations, including older adults and immune compromised people. This program is in the very early stages of development with most platforms and candidate therapeutics in preclinical stages of development. It is likely a few years until this program is ready for phase 2 clinical evaluation.

BARDA will be investing in platform technology improvements that can meet the needs of a PrEP therapeutic. Platform improvements include, but are not limited to, the following:

  • Targeted delivery of nucleic acid therapeutics to the upper and lower respiratory tract, 
  • Inhaled delivery of nucleic acid therapeutics that allow for a minimum of once-a-month dosing,
  • Targeted delivery of monoclonal antibodies (mAbs) to the upper and lower respiratory tract, and
  • Inhaled delivery of mAbs that allow for a minimum of once-a-month dosing.