The COVID-19 pandemic has had significant global consequences, with healthcare systems stretched to their limits, a growing death toll, and economic devastation as economies came grinding to a halt.

The pandemic
and its aftereffects will be with us for some time to come, but this isn’t the
first pandemic humanity has weathered, and it won’t be the last. Given accelerating
advances in medical technology, there is plenty to discuss in terms of how we
can be better prepared for the next infectious disease event.

While COVID-19 is widely thought to have arisen naturally through transmission between an animal and a human, intentional release of an infectious agent, for instance through an act of bioterrorism, could be a factor in future pandemics. Strikingly, this could involve diseases that humans have eradicated in the wild, such as smallpox.

Smallpox is highly contagious with a significant mortality rate, and is estimated to have killed up to 300 million people in the 20th century alone. However, sustained vaccination campaigns led to its eradication by 1980, although known samples of the virus still exist in laboratories in Russia and United States.

If these samples were to be used to create a biological weapon, they could start a smallpox epidemic, as smallpox vaccinations have not been administered for a long time, meaning that very few people now have immunity. Moreover, it is unknown whether those that have been vaccinated in their youth decades ago are still immune to smallpox.

Preparing for
such unlikely, albeit catastrophic scenarios, is something we may need to invest
more time and effort in. One example of an existing defense against a smallpox epidemic
is TPOXX, a pharmaceutical
treatment for smallpox developed by SIGA Technologies
in collaboration with various US government agencies.

Medgadget had the opportunity to discuss approaches to
increasing health security against the next big infectious disease event with
SIGA Technologies CEO, Dr. Phil Gomez.    

Conn Hastings, Medgadget: Please give us an overview of the smallpox treatment offered by SIGA technologies. How does it work and how can it be used? 

Phil Gomez, SIGA Technologies: SIGA Technologies has developed TPOXX® (USAN tecovirimat,
ST-246), the first drug approved by the U.S. Food and Drug Administration (FDA)
that is specifically indicated for the treatment of smallpox disease in adults
and pediatric patients weighing at least 13 kg. TPOXX
inhibits systemic spread of variola virus (the virus that causes smallpox) by
preventing the formation of a secondary viral envelope. In the absence of this
envelope, viral particles remain inside the cell in which they are produced and
cannot spread to and infect other cells.

Although naturally occurring
smallpox was eradicated in 1980 following coordinated, decades-long global
vaccination campaigns, there is growing concern that smallpox could be used as
a bioweapon. A smallpox bioterror attack could be particularly serious because
the majority of today’s population is not immune to the virus, as routine
vaccination ended in the 1970s. Vaccination alone would likely not be effective
in the event of a smallpox bioterror attack due to the fact that vaccine would
need to be administered within 3-5 days of infection to be effective as
therapy, yet symptoms do not appear until 14 days after infection. As the first
antiviral agent specifically indicated for the treatment of smallpox, TPOXX
would play a critical role in responding to a smallpox bioterror attack by
offering a safe and effective treatment to those infected prior to being
vaccinated.

Medgadget: What inspired you to pursue and develop a treatment for a disease that has been eradicated?

Phil Gomez: SIGA has been working in the field of infectious disease since its formation over 20 years ago. As the company scanned its library of existing compounds and acquired new ones, the field of Health Security became an interest in the late 1990s as concerns around potential influenza pandemics and bioterrorism increased. After the anthrax attacks in the United States in late 2001, SIGA focused on the TPOXX molecule in partnership with the U.S. Department of Defense and the National Institutes of Health (NIH) to evaluate its utility for smallpox. The program ramped up rapidly after proof-of-concept studies in non-human primates were successfully completed in 2003.

Medgadget: How might a smallpox outbreak occur? How would it compare with the current COVID-19 pandemic?

Phil Gomez: Smallpox is both highly contagious and highly lethal and there is a significant concern that smallpox could be used as a potential bioweapon. DNA synthesis technology and the possibility of unaccounted for smallpox stocks pose significant risks. While there are two publicly acknowledged stocks of the smallpox virus held by the United States and Russia, some believe that additional stores of the virus could be in the hands of governments or organizations that might use them to cause harm. The DNA sequence of the smallpox genome is in the public domain and could potentially be synthesized in a laboratory from scratch or created by genetically modifying a similar virus.

A smallpox bioterror attack could be especially damaging because
the majority of today’s population is not immune to the virus, as routine
vaccination ended in the 1970s. It is estimated that without vaccination or
treatment, each person infected with smallpox would infect 5–7 others. Rapid
spread from person-to-person can occur through speaking, breathing or touching.
Smallpox also can be transmitted by direct contact with infected fluids and
contaminated objects. Furthermore, vaccination must occur within 3-5 days of
exposure to smallpox, when patients are still asymptomatic, to be effective.
These limitations underscore the need for an effective smallpox antiviral
therapy, in addition to any available vaccine.

In terms of comparison with the current pandemic, smallpox is both
more infectious and more lethal than SARS-CoV-2, the virus that causes
COVID-19. For example, although the data are evolving, it is currently
estimated that each person infected with SARS-CoV-2 can infect 2–2.5 other
people. In contrast, as noted above, it is estimated that without vaccination
or treatment, each person infected with smallpox would infect 5–7 others.
Additionally, while the fatality rate of SARS-CoV-2 has not yet been determined,
the fatality rate among patients with confirmed cases of COVID-19 in the United
States to date appears to be significantly lower than smallpox, which historically
has had a fatality rate of up to 30%. Given the higher infectivity rate and
higher lethality, a potential smallpox outbreak could be more devastating than
what we are experiencing with the current COVID-19 pandemic.

Medgadget: Arguably, humanity was underprepared for the global pandemic we are currently experiencing. What lessons do you think we can learn from this?

Phil Gomez: The field of Health Security has studied and
planned for a pandemic for many years. The United States and other governments
have taken steps that made us more prepared for this pandemic than we would
have been 20 years ago. As a simple example, my lab at NIH was part of the team
that made the first SARS vaccine, which took 20 months to get to the first
human clinical study. That was a tremendous effort, and the “world record” for
vaccine speed in 2003. After many investments in new technologies and further
evolution in efforts to address Ebola, Zika, and influenza, the first
SARs-CoV-2 vaccine was in the clinic in three months.

Having said
that, the overall investment in pandemics has not been sufficient. The
challenge with a pandemic, as we have seen, is that it has an incredible impact
on both human health and the health of the economy. We must make investments in
health security and pandemic preparedness that are proportional to the potential
impact of the problem, and I believe that is the most important lesson we can
learn. In some ways we are fortunate that COVID-19 is not the most dangerous pathogen
that could have caused a pandemic. As noted above, smallpox has higher rates of
fatality and transmissibility. We must make sure we have sufficient quantities
of vaccines, treatments, and diagnostics to rapidly respond to the major
threats, whether they are common threats such as influenza, emerging threats
such as SARS-CoV-2, or threats that seem to be tamed but could re-emerge, such
as smallpox.

Medgadget: Is it feasible to develop, manufacture and stockpile a huge range of vaccines, treatments and equipment for unlikely but potentially catastrophic infectious disease events, or are resources better spent on improving treatments for common illnesses, such as cardiovascular disease and cancer? 

Phil Gomez: The lesson we have learned from COVID-19 is
that a pandemic will have both a tremendous direct impact on human health as
well as a severe adverse impact on the general functioning of the entire
healthcare infrastructure, interfering with the treatment of a very broad cross
section of serious diseases and health conditions. The bottom line, therefore,
is that we must prioritize potential infectious disease and bioterror threats
even as we work to improve prevention and treatment approaches to more common
diseases. To date, most pandemic preparedness investments have been made by the
government while the private sector has played a dominant role in investing in
more common diseases. I think the current pandemic will force a recognition
that all sectors need to work together to ensure that we are appropriately
prepared – and can hopefully obviate or at least better mitigate – the next
pandemic. And hopefully what we learn from increased collaboration in this
arena will also translate into more effective strategies for investing in and
advancing care for other serious and more common diseases.

Medgadget: How will healthcare change in the future as a result of the current pandemic? Do you think we will be better prepared for the next one?

Phil
Gomez:
Yes, I do believe we will be
better prepared for the next one, as we have learned a lot, improved our
planning and increased investments since previous outbreaks. The World Health Organization
has published a report on likely pathogens that could cause future outbreaks,
and I firmly believe we must develop pharmaceutical products (e.g. treatments,
vaccines, diagnostics) for items on that list, and stockpile them globally in
case of future outbreaks. For example, we ought to prioritize development of
“pan-coronavirus” treatments and vaccines. Our drug, TPOXX, was FDA-approved
for the treatment of smallpox, but our R&D program for TPOXX examines other
orthopoxviruses like monkeypox, cowpox, and vaccinia, all of which cause human
disease. Monkeypox cases have been increasing in Africa after the cessation of
smallpox vaccination in the late 1970s and could emerge as a global threat. We
are seeking approval in the European Union and Canada for a broader indication
for TPOXX to treat these other orthopox infections.

I also think we will advance
“platform technologies” for vaccines to ensure we can respond to the next
unknown pathogen rapidly and effectively. Additionally, we must not forget the
importance of diagnostics to understand an outbreak early and monitor the
evolution and response to mitigation.

Finally, I think we will have a different concept of normal after this. Social distancing and awareness of infectious disease transmission will likely change social and business behaviors in ways that will be with us for a long time. I hope to be back with my friends and colleagues soon, but I suspect we will greet each other with a smile and wave rather than a handshake for some time to come. 

Product info page: TPOXX…

Link: SIGA Technologies…



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