Monoclonal antibody antiviral drugs to treat patients with influenza are on track to hopefully be approved by the Food and Drug Administration (FDA) pending further research and trials, according to the Department of Health and Human Services (HHS).
A monoclonal antibody therapeutic drug is a novel approach to treating patients with influenza the development of which is being advanced with funding from the HHS’s Office of the Assistant Secretary for Preparedness and Response (ASPR), HHS announced this week.
According to HHS, “Monoclonal antibodies bind to specific parts of the virus, neutralizing the virus and decreasing the amount of virus in the body.”
Last week, Homeland Security Today reported that HHS’s Office of the Assistant Secretary for Preparedness and Response (ASPR) is working on the development of an experimental influenza antiviral drug that may be more potent and could have a longer treatment window than existing drugs.
The public health community has desperately been investigating new antivirals to combat influenza because more and more strains of influenza increasingly have been found to be resistant to Tamiflu and Relenza, the two primary antivirals used to treat severe cases of influenza.
Meanwhile, researchers from Plymouth University are collaborating with world-leading industrial biotechnology and synthetic biology business Ingenza to develop an efficient, scalable microbial production system for epidermicin, a new class of antibiotic being developed for use in the fight against infections caused by antibiotic-resistant bacteria.
The research team is led by Dr. Mathew Upton, Associate Professor in Medical Microbiology at Plymouth University Peninsula Schools of Medicine and Dentistry, School of Biomedical and Healthcare Sciences.
“This partnership will support the development of an exciting new family of antibiotics that rapidly kill harmful bacteria, even at low doses," Upton stated. These ground breaking new medicines have huge potential to save lives, because they kill bacteria that cause some of the most significant diseases for which there are very few antibiotics left.”
Upton stressed that, “No new classes of antibiotics have been discovered for 30 years and there is a critical need for new antibiotics to treat infections caused by resistant bacteria. If we don’t do this, we risk returning to the time before antibiotics where minor infections could be fatal and routine surgery is not possible. The project will develop methods for producing epidermicin in large amounts, with the ‘lead’ drug investigated for use in human clinical trials for reducing infection following surgery."
Antibiotic resistance has in recent years been identified as one of the biggest threats to global human health. Health services across the world are struggling to contain bacterial infections as the antibiotic arsenal available to them dwindles in effectiveness. It’s estimated that antibiotic-resistant microorganisms cause more than two million infections in the US each year, resulting in at least 23,000 deaths and a cost of $34 billion.
“We’re looking at a little known and largely ignored health crisis secondary to a pandemic or large-scale terrorist bombing like a nuke or something,” a source involved in federal emergency medical preparedness planning told Homeland Security Today in October 2007.
Known as Hospital Acquired Infections, or HAI, these infections can cause serious illnesses and, in severe cases, death. Indeed, infectious diseases are a major cause of illness, disability and death, statistics and authorities point out.
Virologists and emergency public health authorities are alarmed by the thought of a rapidly spreading combination of cytokine storm activating antiviral resistant pandemic flu and antibiotic-resistant Staphylococcus aureus, or MRSA.
"It is now pretty well accepted that one of the precursors for secondary bacterial pneumonia is cytokine storm. Usually the secondary invaders are Streptococcus pneumoniae, Haemophilus influenzae, Chlamydia trachomatis, Mycoplasma pneumonia and Legionella pneumophila," Homeland Security Today was told by a government public health official.
Continuing, the official said "staph can also occur, including MRSA. I think that HAI’s could come from any of these sources if the patient was hospitalized for any length of time. Given the stresses on both hospital systems and personnel during a pandemic, where there is such a profound diminution of both these assets, I believe the likelihood of HAI’s would be increased. These events would compound (extend) the pandemic, but would not fit the strict definition of a separate event."
Consequently, in a mass treatment health care setting, this problem could exacerbate and overwhelm the already overwhelmed emergency care community.
“Yes, of course bacterial infection following influenza should be of concern, and antibiotic resistant bacteria of even greater concern,” the late, world renowned virologist, Laver, told Homeland Security Today before he died.
Pandemic health preparedness authorities, virologists and other scientists expressed alarm over the findings of two studies that indicated a potentially significant number of people died during the horrific 1918 influenza pandemic in part because highly opportunistic bacterial infections were able to flourish in these flu victims because the virus had severely weakened their immune systems.
Prior to relatively recent studies linking virulent influenza to the onset of opportunistic bacterial infections, a team led by Menno de Jong of the Oxford University Clinical Research Unit in Ho Chi Minh City, Vietnam, urged “the focus of clinical [pandemic] management should be on preventing this intense cytokine response by early diagnosis and effective antiviral treatment.”
“If virus replication can be stopped in the early stages, then the likelihood of bacterial infection will be greatly reduced,” Laver said.
The Plymouth University/Ingenza collaboration will work towards developing effective ways to produce epidermicin, which has the potential to be tested in human trials for diseases such as MRSA as a nasal spray. Ingenza’s unique and proprietary genetic and fermentation technologies will accelerate the translation of epidermicin into the commercial reality of scalable, cost effective manufacturing, researchers said.
Back at HHS, “The drug VIS410 being developed by Visterra Inc. of Cambridge, Massachusetts targets a part of the influenza virus that is common to a wide range of flu strains. The target area evolves much more slowly than areas targeted by currently approved drugs, which could allow VIS410 to be effective against flu strains that become resistant to current antiviral drugs," the department stated.
“Having multiple antiviral treatment options available for influenza is essential to saving lives in a pandemic and every day,” said Robin Robinson, Ph.D., director of ASPR’s Biomedical Advanced Research and Development Authority (BARDA) whose office will oversee the project. “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.”
Still, medical authorities told Homeland Security Today they do not know if these new antivirals will also become resistant to new flu strains, or how soon they will need to be administered to patients in order to be effective.
Under a 40-month, $29.1 million agreement with BARDA, Visterra Inc. will conduct clinical studies of the safety and efficacy of VIS410, manufacture materials for use in clinical studies and optimize manufacturing processes. This work will provide support and data needed for the company to submit a request for FDA review and approval of the drug.
HHS said, “The studies also will seek to determine the drug’s efficacy when administered more than 48 hours after the onset of influenza symptoms and to rule out side effects. Current treatment options work best when administered within 48 hours of symptom onset,” although the late renowned virologist Dr. Graeme Laver told Homeland Security Today during extensive interviews before his passing that existing antivirals Tamiflu and Relenza, both of which he played a key role in the development of, optimally should be taken much sooner.
“Early treatment is the only way to go,” he said.
Laver explained to Homeland Security Today that it’s “much better to use Tamiflu only for early treatment. If people with flu symptoms take Tamiflu immediately, say within six or so hours after symptom onset, the infection should be rapidlyterminated, the person should recover, and then, and this is important, should then be immune to reinfection for the rest of the pandemic. Much better than any vaccine. This has been called ‘Aborted-infection Immunization,’ and to use Tamiflu in this way would allow many health care workers and so on to go about their business without fear of reinfection.”
“People will, of course, say, ‘but Aborted-infection Immunization has never been shown to work,’ ” Laver said, adding, “Of course not, but then neither has long-term prophylaxis or the use of pre-pandemic vaccines. But my bet is that it will!”
To work, Laver stressed Tamiflu must be taken in proper doses within 6 to 12 hours after onset of symptoms.
"Forty-eight hours is about the limit the drug is effective," he said.
A former professor of biochemistry and molecular biology at the John Curtin School of Medical Research at the Australian National University in Canberra, Laver studied influenza viruses for nearly 40 years. He and Dr. Robert Webster (another world-renowned virologist at St. Jude Children’s Research Hospital) are credited with having first found the link between human flu and bird flu. In the 1960’s, both received world acclaim when they developed a new and innovative generation of vaccines for flu viruses.
Laver told HHS in 2008 that if antivirals are used prophylaxically, once treatment “is stopped, the person taking Tamiflu is just as susceptible to infection as before. Early treatment would be so much better.”
Laver also strongly believed that Tamiflu and other antivirals should be available over-the-counter [OTC] in pharmacies, where flu victims can get it without the time-wasting need to first get a prescription from a doctor. There is no need for a prescription and the time taken to get one can render Tamiflu pretty well useless, he stated.
“To have people familiar with the correct use of Tamiflu (and Relenza) for seasonal influenza infections would mean the community would be ‘trained’ in the correct use of these drugs in the event of a pandemic. I imagine that, in this case, there would be much less panic than would occur otherwise.”
Laver further stressed that it would be “much better to hold stocks of [antivirals] in every pharmacy in the country, where it can be got quickly after diagnosis by a trained pharmacist or other health care worker.”
Laver also said “using a rapid flu test to assist this would be a good idea, so that people who think they have the flu can be properly diagnosed quickly and take the drugs very soon after symptom onset. This rapid procedure of ‘test and treat’ would mean that the infection should be immediately terminated and the flu victim experience a quick recovery. Seems quite simple, really!”
HHS said, “Pre-clinical studies suggest that VIS410 may be more effective than currently approved antiviral drugs and could be safe and effective in treating patients for whom influenza poses high risks, such as the elderly, children and those with chronic conditions such as chronic obstructive pulmonary disease or heart disease.”
The contract between BARDA and Visterra Inc. could be extended up to a total of five years and $204.5 million. If the contract is extended, the company will conduct larger clinical studies of the drug’s efficacy in severely ill and hospitalized patients including children.
If full development is successful, the drug would provide another treatment option for patients who are hospitalized due to seasonal or pandemic influenza infections. In the United States, more than 200,000 people are hospitalized each year due to seasonal flu complications, and seasonal influenza contributes to approximately 36,000 deaths annually.
The new antiviral monoclonal antibody development project is part of BARDA’s integrated portfolio for advanced research and development, innovation, acquisition and manufacturing of vaccines, drugs, diagnostic tools and non-pharmaceutical products for public health emergency threats. In addition to pandemic influenza, these threats include chemical, biological, radiological and nuclear agents and emerging infectious diseases and antimicrobial resistance.
ASPR leads HHS in preparing the nation to respond to and recover from adverse health effects of emergencies, supporting communities’ ability to withstand adversity, strengthening health and response systems and enhancing national health security.
HHS is the principal federal agency for protecting the health of all Americans and providing essential human services, especially for those who are least able to help themselves.
Editor’s note: This report has been updated to reflect that the FDA has not yet approved monoclonal antibody therapeutic drugs to treat influenza.