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PostPosted: Wed Aug 06, 2014 12:27 am 
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Questions and Answers on experimental treatments and vaccines for Ebola

This FAQ addresses questions the public has about potential treatments and vaccines for Ebola.

For further information on drug development, approval process, and research please contact the appropriate agency:

FDA media office: fdaoma@fda.hhs.gov
NIH media office: niaidnews@niaid.nih.gov
CDC media office: media@cdc.gov
ASPR media office: Gretchen.Michael@hhs.gov

What is ZMapp?

ZMapp, being developed by Mapp Biopharmaceutical Inc., is an experimental treatment, for use with individuals infected with Ebola virus. It has not yet been tested in humans for safety or effectiveness. The product is a combination of three different monoclonal antibodies that bind to the protein of the Ebola virus.

How effective is the experimental treatment?

It is too early to know whether ZMapp is effective, since it is still in an experimental stage and has not yet been tested in humans for safety or effectiveness. Some patients infected with Ebola virus do get better spontaneously or with supportive care. It's important to note that the standard treatment for Ebola remains supportive therapy.

This consists of the following measures:
•balancing the patients' fluids and electrolytes;
•maintaining their oxygen status and blood pressure; and
•treating them for any complicating infections.

Why aren't more people getting ZMapp?

At this time, very few courses of this experimental treatment have been manufactured. Since the product is still in an experimental stage, it is too early to know whether ZMapp is effective. The manufacturer of this experimental treatment continues to research and evaluate the product's safety and effectiveness. It has not yet been tested in humans for safety or effectiveness and much more study is needed.

Did the NIH play a role in getting the experimental therapy to the two U.S. patients in Liberia?

This experimental treatment was arranged privately by Samaritan's Purse, the private humanitarian organization, which employed one of the Americans who contracted the virus in Liberia. Samaritan's Purse contacted the Centers for Disease Control and Prevention (CDC), who referred them to the National Institutes of Health (NIH). NIH was able to provide the organization with the appropriate contacts at the private company developing this treatment. The NIH was not involved with procuring, transporting, approving, or administering the experimental treatments.

Will patients in West Africa be able to access this experimental treatment? How much supply is there?

The product is still in an experimental stage, and the manufacturer reports that there is a very limited supply, so it cannot be purchased and is not available for general use. The manufacturer has been planning for phase 1 clinical trials and does not have the capacity to manufacture large quantities of the treatment. The drug has not gone through clinical trials, meaning its safety and effectiveness has not yet been tested in humans. The manufacturer of the experimental treatment continues to research and evaluate the product's safety and effectiveness.

Is ZMapp available under the Food and Drug Administration's expanded access to investigational drugs?

Currently there are only experimental treatments for Ebola virus infection in the earliest stages of development. When a drug is not approved, the FDA can authorize access to potentially promising products through other mechanisms, such as through an emergency Investigational New Drug (IND) application. In order for an experimental treatment to be administered in the U.S., such a request must be submitted to and authorized by the FDA. The FDA cannot comment on the specifics of ongoing drug development programs and cannot reveal information that is not otherwise public concerning submissions covering such programs such as IND applications submissions. The FDA stands ready to work with companies and investigators treating these patients.

Is ZMapp a vaccine?

No. ZMapp is being developed as a therapeutic product for treatment of people infected with Ebola virus, but not to prevent infection in the same manner as a vaccine. The best way to prevent infection currently is with stringent infection control measures.

What's the difference between therapy and vaccine?

Vaccines are usually given to people before they are exposed to a virus or bacteria that causes a disease. A vaccine stimulates the immune system to generate antibodies and cellular immunity that can fight off an infection if it were to occur. Typically, therapeutics are provided to people who are already infected with the virus. With the experimental ZMapp treatment, the monoclonal antibodies bind to the virus, so that the human immune system can clear the virus.

Are there Ebola vaccines available for use or in development?

There are currently no FDA approved vaccines for Ebola. The NIH's National Institute of Allergy and Infectious Diseases is working on developing an Ebola vaccine. NIH recently announced they are expediting their work, and aiming to launch phase 1 clinical trials of an Ebola vaccine in the fall. NIH is also supporting the Crucell biopharmaceutical company in its development of an Ebola/Marburg vaccine as well as Profectus Biosciences in its development of an Ebola vaccine. Additionally, NIH and the Thomas Jefferson University are collaborating to develop a candidate Ebola vaccine based on the established rabies vaccine.

Is the U.S. government involved in the development of ZMapp?

The U.S. government, specifically, the NIH's National Institute of Allergy and Infectious Diseases, the Department of Defense's Defense Threat Reduction Agency (DTRA), and the HHS' Biomedical Advanced Research and Development Authority (BARDA), has provided support for the development of this experimental treatment.

Are there other companies developing experimental treatments or vaccines?

Two other companies, Tekmira and Biocryst Pharmaceuticals, receive funding from the Department of Defense's Defense Threat Reduction Agency and have therapeutic candidates for Ebola in early development. The Department of Defense is working with a company called Newlink to develop an Ebola vaccine candidate. BioCryst, with NIH support, is working to develop an antiviral drug to treat Ebola virus that is expected to begin Phase 1 testing later this year.
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PostPosted: Wed Aug 06, 2014 10:16 am 
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(Reuters) - Drugmakers' use of the tobacco plant as a fast and cheap way to produce novel biotechnology treatments is gaining global attention because of its role in an experimental Ebola therapy.

The treatment, which had been tested only in lab animals before being given to two American medical workers in Liberia, consists of proteins called monoclonal antibodies that bind to and inactivate the Ebola virus.

For decades biotech companies have produced such antibodies by growing genetically engineered mouse cells in enormous metal bioreactors. But in the case of the new Ebola treatment ZMapp, developed by Mapp Pharmaceuticals, the antibodies were produced in tobacco plants at Kentucky Bioprocessing, a unit of tobacco giant Reynolds American.

The tobacco-plant-produced monoclonals have been dubbed "plantibodies."

"Tobacco makes for a good vehicle to express the antibodies because it is inexpensive and it can produce a lot," said Erica Ollmann Saphire, a professor at The Scripps Research Institute and a prominent researcher in viral hemorrhagic fever diseases like Ebola. "It is grown in a greenhouse and you can manufacture kilograms of the materials. It is much less expensive than cell culture."

In the standard method of genetic engineering, DNA is slipped into bacteria, and the microbes produce a protein that can be used to combat a disease.

A competing approach called molecular "pharming" uses a plant instead of bacteria. In the case of the Ebola treatment, Mapp uses the common tobacco plant, Nicotiana benthanmianas.

The process is very similar. A gene is inserted into a virus that is then used to infect the tobacco plant. The virus acts like a micro-Trojan Horse, ferrying the engineered DNA into the plant.

Cells infected with the virus and the gene it is carrying produce the target protein. The tobacco leaves are then harvested and processed to extract the protein, which is purified.

ZMapp's protein is a monoclonal antibody, which resembles ordinary disease-fighting antibodies but has a highly specific affinity for particular cells, including viruses such as Ebola. It attaches itself to the virus cells and inactivates them.

APPROVAL PROCESS

The drug so far has only been produced in very small quantities, but interest in it is stoking debate over whether it should be made more widely available to the hundreds of people stricken with Ebola in Africa while it remains untested.

“We want to have a huge impact on the Ebola outbreak,” Mapp CEO Kevin Whaley said in an interview at company headquarters in San Diego. "We would love to play a bigger role.”

Whaley said he was not aware of any significant safety issues with the serum. He would not discuss whether the company has been contacted about providing the drug overseas.

But he did note the novel manufacturing process carries its own risk, and would have to be cleared by the U.S. Food and Drug Administration as part of the approval process.

The FDA would, for example, have to be satisfied that the plant extraction process had not led to contamination of the resulting drug.

The tobacco plant grows quickly, said Reynolds spokesman David Howard, and "it takes only about a week (after the genes are introduced) before you can begin extracting the protein."

He declined to say how much medication each plant can yield or whether Kentucky Bioprocessing is in a position to produce ZMapp in significant quantities.

Scripps' Saphire said it can still take anywhere from one to three months to produce the ZMapp serum for wider use given the complexities of the process.

PENTAGON FUNDING

In 2007, Kentucky Bioprocessing entered into an agreement with Mapp Biopharmaceutical and the Biodesign Institute of Arizona State University to refine the tobacco-plant approach. The approach attracted funding support from the Pentagon's Defense Advanced Research Projects Agency (DARPA).

For all the hope, however, the plant technique has delivered few commercial products. In 2012 the FDA okayed a drug for the rare genetic disorder Gaucher disease from Israel's Protalix BioTherapeutics and Pfizer. Called Elelyso, it is made in carrot cells, and is the only such drug to reach the market.

Other companies have fallen far short, though it is not clear if the technique was to blame. Calgary-based SemBioSys Genetics Inc, which used safflowers to produce an experimental diabetes drug, folded in 2012 before it finished clinical trials.

Even Kentucky Bioprocessing, which at one point was developing monoclonal antibodies against HIV (the virus that causes AIDS), C. difficile bacterial infection, and the human papillomavirus, has dropped the last two projects, Howard said.

Last year Mitsubishi Tanabe Pharma Corp acquired a majority share of Quebec City-based Medicago, which is developing influenza and other vaccines using the tobacco-plant technology. The other 40 percent is owned by tobacco giant Philip Morris International.

(Reporting by Sharon Begley, Toni Clarke and Deena Beasley; Editing by Michele Gershberg and Martin Howell)

http://www.reuters.com/article/2014/08/ ... ce=twitter

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PostPosted: Wed Aug 06, 2014 12:32 pm 
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Giving Americans Drug for Ebola Virus Prompts Flak
Liberian Authorities Question Why Two Received Experimental Treatment; Second U.S. Patient Returns From Africa

By CAMERON MCWHIRTER in Atlanta, PETER LOFTUS in Philadelphia and DREW HINSHAW in Accra, Ghana CONNECT
Updated Aug. 5, 2014 11:33 p.m. ET

ATLANTA—As the second U.S. Ebola patient arrived in Atlanta on Tuesday, health authorities in Liberia raised questions about how the woman and an American doctor were given an experimental U.S. treatment unavailable to the hundreds of Africans sickened by the deadly virus.

While still in Liberia, both Nancy Writebol, who was working at an Ebola center for a Christian charity, and Kent Brantly, a physician there, received an experimental drug known as ZMapp. The drug's safety hasn't been tested in humans, and experts said it is too soon to know if it is effective.

For the drug to be used in Liberia, it would have to be approved by the country's Ministry of Health Ethical Committee, said Bernice Dahn, Liberia's chief medical officer.

Dr. Dahn said she wasn't aware of the committee approving any experimental Ebola treatment, though she also wasn't aware of any being disapproved. It is conceivable a treatment was approved without her knowledge, she said. Liberia's assistant health minister, Tolbert Nyenswah, didn't know of any approval. Liberia's presidency also wasn't aware, said Information Minister Lewis Brown.

Now, Dr. Nyenswah said, officials have been beset with requests from dying patients and their relatives for the same treatment.

"This is something that has made our job most difficult," Dr. Nyenswah said. "The population here is asking: 'You said there was no cure for Ebola, but the Americans are curing it?'"

Liberian officials were set to meet Wednesday with the World Health Organization to see about getting the experimental drug rushed into use for other patients, said Dr. Nyenswah.

Ebola, which is usually fatal, causes fever, headaches, vomiting and diarrhea and can cause internal bleeding. The virus is transmitted through bodily fluids. The Ebola outbreak, the largest in history, started in February and has spread through Liberia, Guinea and Sierra Leone.

Details of how ZMapp was administered to the patients in Liberia—and who authorized its use—remained sketchy Tuesday.

Bruce Johnson, president of SIM USA, the Charlotte, N.C.-based charity with which Ms. Writebol, 59, and her husband, David, went to Africa, said at a news conference Tuesday that the decision to use the drug was left to the patients, their families and their doctors.

An Obama administration official said Tuesday that the treatment was arranged by Samaritan's Purse, a humanitarian organization that sponsored Dr. Brantly in Liberia. The National Institutes of Health provided Samaritan's Purse with contacts at the company developing this treatment, the official said.

"The NIH did not procure, transport, approve or administer the experimental treatments in Liberia," the official said.

A spokeswoman for the U.S. Food and Drug Administration said the FDA can provide access to experimental treatments by a mechanism known as an emergency investigational new drug application, and that the agency's approval is required before an experimental drug can be given in the U.S.

Mapp Biopharmaceutical Inc. of San Diego, which developed ZMapp, describes the drug as a cocktail of three "humanized" monoclonal antibodies that are manufactured using tobacco plants. A monoclonal antibody is a laboratory-engineered version of natural antibodies found in humans and animals that help combat disease. Monoclonal antibodies are typically injected or infused; some already on the market treat diseases ranging from cancer to rheumatoid arthritis.

ZMapp was derived from mouse cells that were "humanized," or infused with human components, to work in people, said Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases.

The cocktail comprises components of two older experimental drugs: MB-003, which was developed by Mapp; and ZMab, developed by Defyrus Inc. of Toronto and the Public Health Agency of Canada. MB-003 showed promise in treating monkeys infected with Ebola, according to a study published last year in the journal Science Translational Medicine.

ZMapp is made by infecting tobacco plants with certain proteins, growing them in the plants, then extracting and purifying the proteins, according to David Howard, spokesman for tobacco-products maker Reynolds American Inc. RAI +1.18% A Reynolds unit, Kentucky BioProcessing LLC, has a contract to make the drug in Owensboro, Ky., Mr. Howard said.

Kentucky BioProcessing is working with Mapp and government agencies to increase production of ZMapp, he said. In addition, the company complied with a request from Emory University, at whose hospital the two patients are being treated, and Samaritan's Purse to provide a limited amount of ZMapp to Emory, said Mr. Howard. He declined to say how much was provided. An Emory spokeswoman wouldn't confirm the request.

Ms. Writebol, the patient who arrived in Atlanta on Tuesday, is in stable condition and was able to have potato soup and coffee on Sunday, according to SIM USA. Her husband, who isn't infected, is expected to arrive in Atlanta in a few days.

For 12 years, Emory University Hospital has housed a specially built isolation unit equipped to treat patients exposed to deadly infectious diseases. Ms. Writebol will be in the unit with Dr. Brantly, a 33-year-old doctor from Texas who was infected at the same Ebola center where the two worked. Samaritan's Purse had no updates on his condition Tuesday, but it reported over the weekend that his condition was improving.

Separately, the Centers for Disease Control and Prevention is testing blood from a man who recently returned from West Africa with symptoms consistent with Ebola and has been hospitalized in New York.

Also Tuesday, British Airways said it was suspending flights to Liberia and Sierra Leone this month due to the Ebola scare.

—Colleen McCain Nelson contributed to this article

Write to Cameron McWhirter at cameron.mcwhirter@wsj.com, Peter Loftus at peter.loftus@wsj.com and Drew Hinshaw at drew.hinshaw@wsj.com

http://online.wsj.com/articles/second-e ... 1407256243

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PostPosted: Wed Aug 06, 2014 1:16 pm 
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WHO ‏@WHO 31m
WHO to convene a panel of medical ethicists to explore the use of experimental treatments in the ongoing #Ebola outbreak in West Africa
11:44 AM - 6 Aug 2014 · Details

WHO ‏@WHO 26m
Panel to discuss whether medicines never been tested and shown to be safe in people should be used in the #Ebola outbreak

WHO ‏@WHO 23m
Panel also to discuss given the extremely limited amount of experimental meds for #Ebola available, if it is used, who shld receive it

WHO ‏@WHO 17m
Currently there is no registered medicine or vaccine against #Ebola, but there are several experimental options under development

WHO ‏@WHO 6m
The gold standard for assessing new #medicine involves a series of trials in humans, starting small to make sure the meds is safe to use

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PostPosted: Wed Aug 06, 2014 6:14 pm 
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Ethical Issue: Who Gets Experimental Ebola Drug?
WASHINGTON — Aug 6, 2014, 5:58 PM ET
By LAURAN NEERGAARD AP Medical Writer

The use of an experimental drug to treat two Americans diagnosed with Ebola is raising ethical questions about who gets first access to unproven new therapies for the deadly disease. But some health experts fear debate over extremely limited doses will distract from tried-and-true measures to curb the growing outbreak — things like more rapidly identifying and isolating the sick.

The World Health Organization is convening a meeting of medical ethicists next week to examine what it calls "the responsible thing to do" about whatever supplies eventually may become available of a medicine that's never been tested in people.

At least one country involved in the outbreak is interested in the drug. Nigeria's health minister, Onyenbuchi Chukwu, said at a news conference that he had asked the U.S. Centers for Disease Control and Prevention about access. CDC Director Tom Frieden "conveyed there are virtually no doses available" but basic supportive care can work, a CDC spokesman said Wednesday.

There is no proven treatment or vaccine for Ebola, which so far has infected more than 1,700 people and killed more than 930 in West Africa in what has become the worst outbreak of this viral hemorrhagic fever.

"How many times have we found magic therapies that ended up ... doing more harm than good?" cautioned University of Minnesota professor Michael Osterholm, who advises the U.S. government on infectious disease threats.

"Vaccine and drug treatment right now is not going to be the main way you bring this to a stop," he added.

Scientists stress that there's no way to tell if the experimental drug ZMapp really made a difference for two American aid workers infected while working in Liberia.

"We don't even know if it works," stressed Dr. Anthony Fauci of the National Institutes of Health, which helped fund research that led to the drug's development.

The drug is a cocktail of three antibodies engineered to recognize Ebola and bind to infected cells so that the immune system can kill them. People's immune systems make antibodies to fight off various diseases, and attempts to cull those antibodies — from the blood of people who survive an illness, or from animals — date back to the 19th century and early diphtheria treatment. Using modern techniques to fight Ebola, scientists culled antibodies from laboratory mice, Fauci said, and ZMapp's maker now grows the antibodies in tobacco plants and then purifies them.

Fauci said the manufacturer has told the government that it would take two to three months to produce even "a modest amount." So the NIH is exploring ways to ramp up production, necessary to attempt formal testing or to consider more so-called compassionate use.

"Everybody's trying to speed things up," he said.

To help improve diagnosis in affected countries, the Food and Drug Administration on Wednesday authorized emergency use of an experimental blood test to detect Ebola. Early symptoms — fever, vomiting and diarrhea — can be confused with other illnesses. The test was developed by the Defense Department, and is only for use in DOD-designated laboratories.

This week, the WHO is convening an emergency committee to determine if the outbreak warrants being declared a "public health emergency of international concern," meaning it poses significant risk to other countries and requires more of an international response.

The WHO said that particularly in Liberia, health officials face community resistance from residents who fear going to the hospital and secretly care for ill loved ones at home, thus exposing themselves. Ebola is transmitted only through direct contact with the blood and other bodily fluids of someone who is sick.

But health care workers have to recognize the virus, too. Authorities in Nigeria have acknowledged that they didn't immediately suspect Ebola in the first known patient to travel to that country.

"The bottom line with Ebola is we know how to stop it: traditional public health," said CDC's Frieden said Wednesday: Finding and isolating patients, finding and educating who's been in contact with them and strict hospital infection control.

"Do those things with meticulous care and Ebola goes away," he said.

Minnesota's Osterholm fears those tried-and-true methods could be overshadowed by misunderstanding about any availability of the experimental drug.

"If the Americans had this serum all the time, why didn't they send it to us Africans to help save lives?" said Winston Ojukutu Macauley, a social commentator in Sierra Leone.

But taking an experimental drug requires making sure the patients fully understand there's no proof it will help — and it might even harm, said Osterholm, noting that 40 percent of Ebola patients are surviving. And would it be appropriate for the U.S. to offer a drug to people in developing countries that hasn't been tested on its own citizens?

That's among the things the WHO meeting could address. Even if enough doses were available for wider experimental use, "we need to find a way to do this in a fair manner so that we can live with ourselves when someone asks why this person got it and why not that person?" said Dr. Heinz Feldmann, NIAID's virology chief.

———

AP Medical Writer Maria Cheng reported from London. Associated Press writers Clarence Roy-Macaulay in Freetown, Sierra Leone, and Bashir Adigun in Abuja, Nigeria, contributed to this report.

http://abcnews.go.com/Technology/wireSt ... ePage=true

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PostPosted: Wed Aug 06, 2014 7:34 pm 
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CDC answers questions about Ebola "secret serum" ZMapp
Updated by Julia Belluz on August 6, 2014, 11:00 a.m. ET
@juliaoftoronto julia.belluz@voxmedia.com

There has been a flood of interest about the experimental serum used to treat the American Ebola patients, so the Centers for Disease Control and Prevention just released their answers to common questions that have been popping up. For example:
Image

Patients

They basically outline that this treatment is still very much at the pre-human phase of clinical trial development, and so it's a long way off from reaching patients. You can read more here.

This effort is part of CDC's response to public interest and anxiety over Ebola. Time magazine reported that there has been a flurry of worried callers to the agency over Ebola in recent weeks. "We've triaged those calls and about half-dozen or so resulted in specimen coming to CDC for testing and all have been negative for Ebola," CDC spokesman Tom Skinner told Time.

In this StoryStream
Ebola outbreak: the deadliest in history
11:00A
CDC answers questions about Ebola "secret serum" ZMapp
AUG 5
American Ebola victims are the subjects of a science experiment
25 updates

http://www.vox.com/2014/8/6/5974809/cdc ... erum-zmapp

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PostPosted: Thu Aug 07, 2014 8:09 am 
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Ebola Therapy From an Obscure Biotech Firm Is Hurried Along
By ANDREW POLLACKAUG. 6, 2014

Inside special isolation units at an Atlanta hospital on Wednesday, Kent Brantly and Nancy Writebol, the two Americans infected with Ebola in West Africa, appeared to be responding to an experimental medicine devised by an obscure biotechnology company with ties to the Defense Department.

In West Africa, the estimated death toll from the outbreak kept rising, to 932, by the latest official count.

How and why Dr. Brantly and Ms. Writebol received the drug, ZMapp, is one of the many mysteries surrounding what has been called a “secret serum,” including the big one: Does it really work? The Americans are the only two patients who have been treated with the medicine, out of perhaps thousands who might have benefited so far, raising old questions about who does — and does not — have access to medications, including experimental drugs.

A Reynolds American plant in Owensboro, Ky., makes ZMapp inside the leaves of tobacco plants, but production is very limited. Credit Kentucky Bioprocessing, via European Pressphoto Agency
“It’s absolutely overwhelming,” Larry Zeitlin, the president of Mapp, said in an interview Wednesday. “We are discussing with the F.D.A. the right path to make the drug available to people as quickly and safely as possible,” he added, referring to the Food and Drug Administration.

There were signs that efforts to increase production were beginning. Caliber Biotherapeutics, a Texas company established with funding from the Defense Department to respond to biological threats, has received inquiries from the government about whether it could help manufacture ZMapp, said R. Barry Holtz, the company’s chief science and technology officer.

The World Health Organization said it would convene a panel of medical ethicists early next week to explore the use of the experimental treatment in the outbreak in West Africa. Currently, neither ZMapp nor any other medicine or vaccine is approved for treatment of the virus, but there are several experimental options under development.

How quickly the drug could be made on a larger scale will depend to some extent on the tobacco company Reynolds American. It owns the facility in Owensboro, Ky., where the drug is made inside the leaves of tobacco plants. David Howard, a spokesman for Reynolds, said it would take several months to scale up.

Mapp was started in 2003 by Dr. Zeitlin and Kevin J. Whaley. They have worked together for many years, starting at Johns Hopkins University, on research that uses crops to produce immune system proteins to treat diseases in people.

Dr. Whaley, the chief executive of Mapp, and Dr. Zeitlin have not spoken much publicly since the news of the treatment broke on Monday, saying they are too busy and want to avoid the limelight. The privately held company has only nine people and has been financed solely by government grants and contracts, they said.

“We definitely would like to ramp up to have an impact on the Ebola epidemic,” Dr. Whaley said. But he added, “We’re not decision makers on many of these issues. There are regulatory and legal issues that have to be addressed.”

The drug had never before been tried in people, though it and some predecessor drugs had been tested in monkeys, showing some effectiveness. Mapp was only now gearing up to start the larger animal toxicity studies typically needed before testing it in humans, with an eye to doing the first human safety studies in healthy volunteers next year. For that reason there were very few doses available when the Ebola outbreak started.

Now the company is trying to move faster and it is likely the drug will be tested in patients rather than healthy volunteers.

ZMapp uses an approach called passive immunotherapy. Instead of having a vaccine stimulate the immune system to make antibodies that attack the virus, passive immunotherapy simply supplies the antibodies to the patients. For some infectious diseases, these antibodies are extracted from the blood of patients who have survived the infection and presumably have effective antibodies.

ZMapp instead consists of antibodies that are made by exposing mice to a key Ebola protein and harvesting their antibodies. Those antibodies are then genetically modified to make them more like human antibodies and therefore less likely to provoke an immune reaction if injected into people.

The gene for each antibody is then introduced into the leaves of tobacco plants using a system developed by Icon Genetics, a German company. The leaves then produce the antibody.

In one study published last year, three out of seven monkeys treated with antibodies developed by Mapp survived being infected with Ebola, even though treatment did not start until four days after the infection. Both animals in the control group died. The treatment worked even better in another study when begun earlier after exposure to the virus.

It turns out another tiny company, Defyrus, based in Toronto, was independently developing a similar treatment with the Public Health Agency of Canada.

The companies agreed to combine the best of their antibodies into a single cocktail called ZMapp, which is what the two American aid workers received. The data for ZMapp in monkeys has not been published but is said to be substantially better than for the predecessor drugs.

Dr. Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases, said it was “too early to make any conclusions about how effective this intervention is,” since it was tested in only two people.

Still, there is interest in scaling it up.


Monoclonal antibodies produced by pharmaceutical companies for use in treating cancer or other diseases are typically made in genetically engineered cells of mammals grown in vats. But Mapp chose to use plants instead because large quantities can potentially be produced more quickly and cheaply.

About 15 years ago, it was thought that genetically engineered crops would be widely used to produce human proteins for use as drugs. When Dr. Whaley and Dr. Zeitlin were both researchers at Johns Hopkins University in 1998, they published a paper with Monsanto scientists about a soybean genetically engineered to produce an antibody against genital herpes. But that idea has largely been abandoned, especially when it comes to using food crops, because of concerns that drugs produced in crops might inadvertently get into someone’s cornflakes.


Even so, research has continued, funded by the Defense Department, on quickly producing proteins in tobacco plants that are grown inside buildings.

“You can start making protein within a matter of days,” said Robert L. Erwin, president of iBio, another company that is working on this technology.

Still, it seems that this product will take several months to produce in any quantity. The capacity of the Kentucky facility is small, meant to support only the small scale human safety tests that Mapp had been planning. The tobacco plants have to be grown for about a month before they can be infected with the antibody gene and the proteins have to be harvested and purified.

“Starting from zero and going to 60 is not so easy, but once you’re at sixty you can keep going at that rate,” Dr. Whaley said. He would not say how many doses could be made and how quickly.


Dr. Fauci of the infectious diseases institute said officials had been told it would be a moderate amount even after several months. “You’re not talking about thousands of doses or even hundreds of doses,” he said.

But there are some other companies that can also make drugs in tobacco, including Caliber, which has a larger capacity than the Kentucky facility. So the government is exploring using them to supplement production.

“We told them we have the capacity and are ready,” said Dr. Holtz of Caliber. He said that together Caliber and the Kentucky facility of Reynolds could produce large quantities in six months.

Dr. Michael V. Callahan, an infectious disease specialist at Massachusetts General Hospital who has responded on the ground to Ebola outbreaks, said the use of ZMapp for the two Americans raised some concerns given the limited existing supply. “What was the prioritization that allowed these patients to be treated?” he said.

According to the Department of Health and Human Services, the reason was that Samaritan’s Purse, the organization that employed one of the aid workers, contacted the Centers for Disease Control, which in turn referred them to National Institutes of Health, which in turn referred them to Mapp.

Doing clinical trials in Africa will likely require approvals from authorities there. And treating large numbers of patients with ZMapp, which needs to be given intravenously, could be difficult.

“What can you give in an austere treatment environment where there is very little nursing care?” asked Dr. Callahan. Authorities, along with the San Diego biotech company, are trying to figure it all out. Dr. Zeitlin said, “We’re kind of in uncharted territory here.”

A version of this article appears in print on August 7, 2014, on page B1 of the New York edition with the headline: An Obscure Biotech Firm Hurries Ebola Treatment. Order Reprints|Today's Paper|Subscribe

http://www.nytimes.com/2014/08/07/busin ... share&_r=0

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PostPosted: Fri Aug 08, 2014 1:07 pm 
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Title:Next-Generation Monoclonal Antibodies: Challenges and Opportunities
Authors:Gigi Kwik Gronvall, Kunal J. Rambhia, Amesh Adalja, Anita Cicero, Tom Inglesby, and Robert Kadlec
Publication: Center for Biosecurity of UPMC, February 15, 2013
Publisher:This project was supported by DTRA Chem Bio Directorate, and in collaboration with TASC, Inc, under contract #HDTRA1-11-D-0004.
Date posted: February 15, 2013
See also:
Full Report (PDF) • Video Brief with Dr. Gigi Gronvall
Introduction:
The Center for Biosecurity of UPMC conducted this study to provide leaders in the US Department of Defense (DOD) with an expert assessment of the technical feasibility and strategic implications of next-generation monoclonal antibodies (mAbs) as medical countermeasures (MCMs) for DOD personnel. Our assessment includes identification of potentially appropriate DOD investments in mAb technologies.
SUMMARY OF FINDINGS

As a technology platform, monoclonal antibodies have value for DOD as a defense against bioweapons and emerging infectious diseases.

Monoclonal antibodies have great potential usefulness to counter biological warfare agents and naturally occurring infectious disease threats that are not addressed by currently available countermeasures. Monoclonals display exquisite specificity, are able to recruit additional host immune components to fight infection, confer near-immediate immunity once administered, can be successfully administered to all populations regardless of current immune status, and have a generally low rate of adverse reactions. Further, mAbs may offer pre- and postexposure protection in addition to potential therapeutic benefits, even in the case of antibiotic resistance. There is also a body of scientific evidence that mAbs may be effective in treating disease caused by biological warfare and natural pathogens of concern to DOD.
Although commercial development of mAb technologies is mature, mAbs are not commonly used to prevent or treat infectious diseases.

Monoclonal antibodies have become a commercial blockbuster drug platform, with the biggest portion of sales growth in the pharmaceutical industry. However, the concentrated effort in monoclonal antibody development has focused on oncological indications and immunological diseases, such as rheumatoid arthritis (RA). There is one commonly used licensed product for prevention of respiratory syncytial virus (RSV) in premature babies, another recently FDA approved for inhalational anthrax disease, and a handful of mAb products undergoing clinical evaluation for infectious disease indications, including methicillin-resistant Staphylococcus aureus and Clostridium difficile.
mAbs are poised to play a critical role in infectious disease management.

In spite of the lack of commercial attention to infectious disease mAbs, there are a number of reasons to believe they may be more desirable in the future, because of the declining clinical effectiveness of antibiotics; the large number of immunocompromised people who could benefit from mAbs; the growing recognition of the microbiome, which is disrupted by antibiotics; and the increased availability of diagnostic tests that may make mAbs more feasible to administer. In addition, because many infectious disease indications may require administration of a cocktail of mAbs, it is encouraging that the FDA has allowed cocktails of mAbs to be clinically tested as one product.
High cost per dose is a hallmark of mAbs, but costs are dropping.

Monoclonal antibodies are expensive. As a biologic class of drugs, they cost more to manufacture than small-molecule drugs, and FDA-licensed mAbs are currently among the most expensive drugs for patients and insurance companies. Many factors contribute to the cost of a particular mAb, but the most important factor influencing their price appears to be the market—the market will bear a high cost for mAbs, so they carry a big price tag. Some indicators suggest the cost of mAbs is dropping; this has been attributed to insurance company actions and greater mAb manufacturing standardization.
Monoclonal antibody products have greater regulatory success than other drug classes, but all biodefense products share common regulatory risks.

Monoclonal antibodies, in general, do not carry as much regulatory risk as other medical countermeasures, and the FDA has recent and historical experience with evaluating mAb products. This makes mAbs especially attractive for DOD, which is required to use only FDA-approved MCMs for prevention and treatment. However, biodefense products in general are riskier than other MCMs because they often require application of the FDA Animal Efficacy Rule, which allows for FDA approval based on animal model efficacy data and human safety data.
Areas for Action by DOD

As a class, mAbs will not replace vaccines or drugs in a complex MCM strategy, but they can be an important adjunct of a comprehensive approach that may be well-suited for specific DOD populations and for specific pathogens. Therefore, the question confronting DOD is not whether mAbs should be employed, but how to use mAbs technologies effectively. This report recommends that DOD take the following actions to take advantage of mAb technologies:
Include mAbs as part of the DOD medical countermeasure strategy.
Develop a library of mAbs that are IND-ready (ie, have attained investigational new drug status) and can be used as prophylaxis or treatment against a range of pathogens.
Consider fast-tracking 3 mAbs for development as a proof of concept: one for treatment of a high-risk bacterial pathogen, one for prophylaxis against a fast-moving virus, and one for prophylaxis against a toxin.
Establish partnerships with mAb developers by describing clear, specific requirements for mAbs that will be needed and pursued.
Engage private industry and academia in mAb research and development (R&D) through clearly defined research partnerships, such as precompetitive consortia to develop new mAb technologies, which may also accelerate the lowering of production costs.
Invest in R&D for improved means of mAb administration that meet DOD operational requirements.
Leverage R&D of mAbs to enhance ongoing efforts to develop rapid point-of-care diagnostics.
http://www.upmchealthsecurity.org/our-w ... ortunities

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PostPosted: Fri Aug 08, 2014 6:31 pm 
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Federal panel to ponder using Ebola drugs; FDA eases hold on one
The Obama administration is setting up an Ebola working group to consider making policy for the possible use of experimental drugs in West Africa's Ebola epidemic, Reuters reported yesterday, while the Food and Drug Administration (FDA) lifted a barrier to the potential use of an unlicensed drug made by a Canadian company.

There are no licensed drugs for Ebola, but several companies have experimental drugs. Two infected American medical workers were recently treated with one of them, ZMapp, and some are advocating broader emergency use of candidate drugs.

An unnamed Obama administration official told Reuters the working group is being formed under Nicole Lurie, assistant secretary for preparedness and response at the Department of Health and Human Services.

The group will include officials from such agencies as the National Institutes of Health (NIH) and the Centers for Disease Control and Prevention (CDC), said Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases (NIAID).

Fauci told Reuters he was unsure when the group would meet or who would be there, but said, "I'm sure they'll tap people from NIAID with competence in clinical trials. . . . You need to balance compassion with the need to figure out if something actually works."
Aug 7 Reuters story

Meanwhile, the FDA has loosened its "full clinical hold" on TKM-Ebola, an experimental drug made by Tekmira Pharmaceuticals of Vancouver, B.C, permitting its potential use in Ebola patients, the company announced yesterday.

In a press release, Tekmira President and CEO Mark Murray, PhD, commented, "We are pleased that the FDA has considered the risk-reward of TKM-Ebola for infected patients. We have been closely watching the Ebola virus outbreak and its consequences, and we are willing to assist with any responsible use of TKM-Ebola."

Tekmira said the FDA's hold on clinical use of the drug still applies to the "multi-ascending dose portion" of a phase 1 clinical trial.

TKM-Ebola is being developed under a $140 million contract with the US Department of Defense. In an earlier study, the drug protected monkeys from an otherwise lethal dose of Ebola Zaire virus.
Aug 7 Tekmira press release

http://www.cidrap.umn.edu/news-perspect ... ug-08-2014

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PostPosted: Mon Aug 11, 2014 8:40 am 
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Petitioning Makers of ZMapp, United Nations and CDC
The experimental drug ZMapp should be made available immediately in Guinea, Sierra Leone, Liberia and Nigeria.
Image

Petition by
Ify Asogwa
London, United Kingdom

The latest Ebola virus outbreak has quickly become a continental epidermic and countries in Africa are struggling to contain the spread. There is a danger that if not contained it could spread like wildfire resulting in the needless loss of valuable human lives in the countries in West Africa that have reported cases of infections.

We have read with interest and dismay of the 2 Americans and 1 Spanish that were infected with Ebola and have been evacuated by their countries then treated with the experimental drug ZMapp. ZMapp has been successful in helping their recovery from the Ebola virus which is known to have a 90% mortality rate. The countries where these individuals are from were able to procure this expereimental drug ZMapp quickly enough to prevent the loss of their lives. This is in contrast with the lives of people in West Africa that are dying everyday as the disease continues to spread and the health authorities struggle to contain it.

Guinea, Sierra Leone, Liberia and Nigeria , the four countries in Africa battling with the Ebola outbreak have requested access to ZMapp and instead of this live saving medicine being provided immediately in order to save lives and prevent the outbreak of a epidermic that would be a contiental disaster, they are still embroiled in the bureaucratic processes which were obviously waivered for Spain and the US citizens.

I invite you to stand with me and the people in Guinea, Sierra Leone, Liberia and Nigeria who are under immediate threat from this global epidermic and sign this petition calling on the makers of ZMapp, the United Nation and The Centers for Disease Control and Prevention , United States to provide immediate access to this life saving medicines.

We believe Every human life is VALUABLE and deserves to be fought for. If you believe the same then please sign this petition and share it on social media.

LET'S GET THE WORLD TO ACT NOW TO SAVE LIVES.

To:
Makers of ZMapp, United Nations and CDC, LeafBio, Inc. 6160 Lusk Blvd. #C104 San Diego, CA 92121 VM/Fax 858 625 0335
Ban Ki-moon, Secretary General, United Nations, 1st ave. and 46th street New York, NY 10017 USA
CDC, Dr. Tom Frieden, Centers for Disease Control and Prevention 1600 Clifton Rd. Atlanta, GA 30333 USA
Dr Gro Harlem Brundtland, Director General , WHO, Avenue Appia 20 CH-1211 Geneva 27
The experimental drug ZMapp should be made available immediately in Guinea, Sierra Leone, Liberia and Nigeria.
Sincerely,
[Your name]

http://www.change.org/en-GB/petitions/m ... e_petition

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