HHS offers some forecasts on medical countermeasures

Dec 11, 2012 (CIDRAP News) – A new report from the US Department of Health and Human Services (HHS) offers a few predictions on when certain new countermeasures against biological threats will become available, including a forecast for two novel influenza drugs and possibly a next-generation anthrax vaccine within the next 5 years.

The 2012 Public Health Emergency Medical Countermeasures (PHEMCE) Implementation Plan outlines expected developments for the next few years for anthrax, smallpox, pandemic flu, botulism, and other bacterial and viral threats.

It says HHS's Biomedical Advanced Research and Development Agency (BARDA) "will support advanced development of at least two drugs with novel mechanisms of action through Phase III clinical studies; two drugs are expected to be approved in the U.S." in fiscal years 2015 to 2017.

The report also says that two more flu antivirals are expected to be approved in the long term, meaning in fiscal 2018 or later.

The report doesn't name the drugs, but BARDA Director Robin Robinson, PhD, noted that one of the antivirals BARDA is supporting is NexBio's Fludase, also known as DAS181. "This product candidate inhibits a cell surface molecule rather than a viral target like currently licensed flu antiviral drugs," he told CIDRAP News.

On Oct 3 BARDA announced a $26.5 million contract for further development of Fludase, saying it could be effective against all known flu strains, including ones resistant to existing antivirals. The major existing US-approved drugs, oseltamivir (Tamiflu) and zanamivir (Relenza), are neuramindase inhibitors, which work by blocking newly hatched viral particles from exiting infected cells.

Robinson said other flu drugs in the pipeline include laninamivir and intravenous zanamivir, both of which are neuraminidase inhibitors. Laninamivir, marketed in Japan under the name Inavir, is a single-dose, long-acting drug given by inhaler. It is also known as CS-8958.

In 2011 BARDA awarded Biota Scientific Management of Melbourne, Australia, a $231 million, 5-year contract to establish manufacturing of laninamivir in the United States and to support clinical trials.

Laninamivir was developed by the Japanese company Daiichi Sankyo but is co-owned by Biota, according to previous reports. It was approved in Japan in 2010.

Second of two reports
The 60-page PHEMCE Implementation Plan follows up on a report that was released in June, the 2012 HHS PHEMCE Strategy. The two documents explain the government's plans for developing medical countermeasures to protect the US civilian population from chemical, biological, radiological, and nuclear weapons.

The PHEMCE is described as the coordinating body for the federal agencies in charge of the countermeasures, which include medicines, vaccines, devices, and other interventions.

The implementation plan is intended to explain how the government prioritizes medical countermeasures spending. The three prioritization criteria are (1) addressing the most significant threats, (2) fostering approaches with the potential to provide protection against multiple threats, and (3) maintaining the ability to use the countermeasures developed.

Other criteria that influence priorities include addressing the needs of the whole population, including vulnerable groups, balancing rapid acquisition of countermeasures against gains in capabilities that may be achieved through other long-term efforts, and considering the life-cycle costs of countermeasures.

Much of the implementation plan addresses four broad goals and general approaches for achieving them. One section focuses on specific threats and the plans for defending against them, listing near-term (fiscal 2012-14), mid-term (2015-17), and long-term (2018 and later) plans.

Anthrax defenses
The report predicts that the long-sought goal of a next-generation anthrax vaccine may become available in the mid term (2015-17). It notes that multiple recombinant protective antigen (rPA) vaccines are in the development pipeline.

In the same time frame, the report says, BARDA will support expansion of the domestic manufacturing capacity for the existing anthrax vaccine, made by Emergent BioSolutions. The effort will include validating new manufacturing processes, conducting additional non-clinical and clinical studies, and pursuing licensing of a new facility.

In near-term anthrax vaccine efforts, the National Institutes of Health (NIH) is working to improve the existing vaccine by developing and testing adjuvants that could improve its performance and reduce the number of doses required, the report explains. Clinical testing of adjuvants is under way, and advanced development is expected by fiscal 2014.

The existing vaccine is given to US military member who serve in high-risk parts of the world; it requires five doses over 18 months.

BARDA is also supporting efforts to expand the existing vaccine's indications to include postexposure prophylaxis and extend its shelf life, the report notes.

Pandemic flu activities
The report discusses a wide range of pandemic flu countermeasures in addition to new antivirals.

For the near term, the NIH "is focusing on a wide array of novel viral antigen and universal influenza vaccine concepts, with several candidates entering preclinical development over the next several years," the report says. The agency expects to move several universal vaccine candidates into early clinical trials in the mid term.

Further, "BARDA will support at least one novel viral antigen or universal vaccine candidate expected to be evaluated in Phase II clinical studies in the mid term," the report states.

In a recent comprehensive report on flu vaccines, experts at the University of Minnesota said few of the many vaccines now in development are truly innovative, in the sense of using an antigen other than the head of the virus's hemagglutinin protein. Hemagglutinin constantly evolves to evade the immune system, which necessitates reformulation of the vaccine each year. The report was written by a team from the university's Center for Infectious Disease Research and Policy, which publishes CIDRAP News.

The PHEMCE report notes that for the intermediate and long term, cell-based and recombinant-based flu vaccines are key elements of the US pandemic flu strategy, with the aim of providing domestic manufacturing surge capacity.

A the Centers for Disease Control and Prevention, experts will continue refining the Influenza Risk Assessment Tool (IRAT), designed to measure the pandemic risk of influenza A viruses that are circulating in animals but not in humans, according to the report.

Also, the CDC aims to seek approval in the near term for a test to distinguish the two major lineages of influenza B.

The report also discusses plans to develop and maintain defenses against smallpox and botulism. On the smallpox front, plans include publishing within the next 2 years a guidance document on national vaccination strategies to be used if a smallpox case occurs.

See also:

Dec 9 PHEMCE Implementation Plan

Implementation plan fact sheet

Oct 3 HHS press release about Fludase contract

Oct 15 CIDRAP News story "Report: Complacency, misperception stymie quest for better flu vaccines"

Jun 27 CIDRAP News story "HHS updates medical countermeasures strategy"

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