A New Hope with a new drug for H1N1 Flu

Athena Gurno thought her allergies were acting up when she started coughing in early October. But within days, Ms. Gurno, the 30-year-old mother of a young girl, was in a Seattle hospital, close to death from the H1N1 flu.

Desperate, her doctors tried a still-experimental drug called peramivir. After getting her second dose, Ms. Gurno started to recover, though she is still in intensive care, according to her father, John Spikowski.

“This saved Athena’s life,” Mr. Spikowski reported on a blog that tracks his daughter’s progress.

Peramivir might also be a life saver for its developer, BioCryst Pharmaceuticals, an unprofitable biotechnology company in Birmingham, Ala., that was founded in 1986 but has not yet had a drug reach the market.

On Thursday, the federal government ordered, on an emergency basis, 10,000 treatment courses of peramivir for its national stockpile. It is paying $22.5 million, or about $2,250 a patient. Shares of BioCryst rose nearly 13 percent, to $11.39.

Peramivir is given intravenously, making it usable by hospitalized patients who are too ill to take two approved flu drugs that work against the virus in similar ways — Tamiflu by Roche, which is typically given as a pill, or Relenza from GlaxoSmithKline, which is inhaled.

Late Thursday, the government announced orders for intravenous versions of Tamiflu and Relenza, which are much cheaper — a development that could force shares of BioCryst to give up some of their gains on Friday.

Peramivir, still being tested in clinical trials, is not approved by the Food and Drug Administration for general use. But on Oct. 23, the F.D.A. granted authority for the drug to be used in emergencies for patients hospitalized with H1N1 flu who cannot take or do not benefit from Tamiflu or Relenza.

Before that, peramivir had been available only through a more cumbersome “compassionate use” procedure. Of the 32 patients who received the drug that way, 29 were still alive, BioCryst said in late October.

Although there are still questions about peramivir’s true effectiveness, some critics say the government moved too slowly to make the drug available, and that even now, access is too restricted. For each patient, doctors must call an 800 number or fill out a form on a Web site run by the Centers for Disease Control and Prevention. The drug is then sent overnight from a central stockpile.

“If you have a critically ill patient, to delay therapy, it’s just incomprehensible to me,” said Dr. Richard Whitley, a professor at the University of Alabama and the president of the Infectious Diseases Society of America. He said the drug should be distributed so that hospitals could have it in stock.

But Dr. Nicole Lurie, assistant secretary for preparedness and response at the Department of Health and Human Services, said the limited supplies made more general distribution impossible. Some doctors said they were satisfied with the existing system.

“I think it’s fairly accessible,” said Dr. Thomas M. File Jr., chief of infectious diseases at Summa Health System in Akron, Ohio, who has treated a pregnant woman with peramivir. Some of the push to make the drug more widely available is coming from investors in BioCryst, including Kleiner Perkins Caufield & Byers, the prominent Silicon Valley venture capital firm. John Doerr, the company’s technology guru, was in Washington this week making the case for greater availability of peramivir, according to a person who met with him there.

Other investors — both supporters of BioCryst stock and those betting the price will fall — have commented at government meetings on flu preparations, often without revealing their financial interests.

Anecdotes like Ms. Gurno’s aside, the efficacy of peramivir is still in question, according to the government. While some clinical trials showed the drug had an effect in resolving flu symptoms, others did not show statistically significant differences between peramivir and either a placebo or Tamiflu.

The question for both investors and federal authorities is how much more of the drug BioCryst can sell. So far, the order has been far less than some investors had hoped, though the price of the order announced Thursday was higher than expected.

Dr. Lurie, the federal official, said there had been 237 requests to use the drug since the emergency use authorization was granted nearly two weeks ago. Many doctors want to provide the treatment for 10 days instead of the recommended 5, she said, so the 10,000 courses the government ordered might actually treat as few as 5,000 patients.

The government has the right to buy up to 30,000 more treatment courses at the same price.

BioCryst says it will have perhaps 40,000 more treatment courses available within a few weeks, and a total of 120,000 by the end of the year. It also says it has signed up partners to try to win sales in Brazil, Mexico, Israel and China.

“We’re getting a lot of interest from countries outside the United States,” Jon P. Stonehouse, the company’s chief executive, said in an interview Thursday.

Shionogi, a Japanese drug company with licensing rights from BioCryst, ran its own clinical trials and this week applied for approval to sell the drug in Japan as a treatment for everyday flu, in competition with Tamiflu.

But in the United States, BioCryst plans to try to win approval for treatment only of hospitalized patients. It is now beginning phase 3 trials — the last stage before seeking F.D.A. approval.

Virtually all the money to develop the drug comes from $180 million in grants from the Department of Health and Human Services. Yet the company gets to keep as profit anything it makes from selling the drug to the federal government or to other governments. Mr. Stonehouse defended the price of the drug, saying it would save the health system money by getting patients out of intensive care earlier. “The cost of being in the I.C.U. and on a ventilator is extremely high,” he said.

But peramivir will soon have competition. The federal government said late Thursday that it had also ordered 10,000 treatment courses each of intravenous versions of Tamiflu and Relenza, with options to buy 30,000 more courses of each.

Those drugs could not be used, however, until they received emergency use authorizations from the F.D.A.

The government is paying an average of only $450 a course for those other drugs — only one-fifth of what it is paying for peramivir.

Right now, Dr. Lurie said, peramivir is the only drug that can be used intravenously so the government had to pay a high price. “I would say that one of the things that happens in the market when you have competition is that the price drops.”

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One-dose drug to fight flu

A New antiviral drug requiring only one dose is close to reaching the market, after Australian developer Biota announced successful trials in Asia.

The drug - laninamivir - is a potential successor to the firm's Relenza, which along with Tamiflu is taken for swine flu.

The new drug can be taken once to treat flu, or weekly as a preventative. The alternative drugs must be taken every day.

Biota managing director Peter Cook said commercial availability was ''within sight'', after trials in Japan, Taiwan, Hong Kong and Korea proved it safe and effective. Trials on adults and children found a single dose worked just as well to rid patients of the flu as taking Tamiflu twice a day for five days.

In children, the drug got rid of the illness more quickly than the Tamiflu regimen.

Biota's partner Daiichi Sankyo will apply to Japanese authorities to manufacture and market the drug next year.

However, before Biota can get market approval in the US and Australia, it must complete more trials that compare its performance with a placebo.

Mr Cook said the single dose meant national stockpiles against flu pandemics would be easier to build - and it could ensure patients completed a course of antivirals. He said it was effective against seasonal, avian and swine flu strains.

Increasing the range of antiviral drugs would slow the spread of resistant strains of influenza. Several strains of seasonal flu have already proven resistant to Tamiflu, and there are early signs in laboratory tests of some resistance to Relenza.

Like Relenza, the new drug is taken with an inhaler device, which restricts its use in children. Like Relenza and Tamiflu, the new drug works by preventing the spread of viruses from the lungs to elsewhere in the body.

Source : www.theage.com.au

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Regular flu vaccine little help against new strain

The seasonal flu vaccine provides virtually no protection against the new H1N1 influenza strain, federal health researchers confirmed on Thursday.

Their study using stored blood samples supports an intriguing theory that people over the age of 60 have some immunity to the new H1N1 strain, perhaps because it resembles an older version of seasonal flu.

The findings are important as U.S. and global health officials grapple with the question of whether to offer a vaccine against the new swine flu virus, which has infected more than 11,000 people globally and killed at least 85.

They also illustrate the need for a so-called universal influenza vaccine -- one that can protect people from a range of strains of the constantly changing virus.

"We would love to have an influenza vaccine that did not have to be reformulated each year," Dr. Anne Schuchat of the U.S. Centers for Disease Control and Prevention said at a news briefing.

The researchers at the CDC, Food and Drug Administration, National Institute of Allergy and Infectious Diseases, along with, universities and vaccine makers, looked at blood samples given after people were vaccinated for seasonal flu.

Seasonal flu vaccines carry an H1N1 component, an H3N2 strain and an influenza B strain. They tested these samples against both seasonal flu viruses and the new H1N1 strain.

Blood from children showed no immune system protection from the new strain, they wrote in the CDC's weekly report on death and disease.

PRE-EXISTING IMMUNITY

"Results among adults suggest that some degree of pre-existing immunity to the novel H1N1 strains exists, especially among adults aged over 60 years," the researchers added.

One possible explanation is that older adults were either infected with or vaccinated against a much older strain that more closely resembles the new H1N1 strain.

Schuchat said it is odd that genetic analysis shows the new swine flu virus is very different from any other H1N1 virus seen previously. There may be an aspect to flu viruses that the human immune system recognizes that does not show up in the genes, she said.

"We are wondering whether there were viruses around in the 1930s, 1940s, 1950s that were immunologically similar," she said.

The H1N1 family of flu viruses was first documented when it caused the 1918 influenza pandemic. H1N1 viruses have been circulating among humans and pigs on and off since then but with frequent mutations and shifts.

Because of these changes, the seasonal flu vaccine must be reformulated every year.

Schuchat said the tests done for the study cannot show whether the immunity seen in the blood samples was enough to protect people from infection with the new strain.

On Thursday the CDC reported 5,764 confirmed U.S. cases of the new flu and nine deaths. Schuchat said it is likely more than 100,000 people have been infected.

An unusually high proportion of those being infected and hospitalized with serious disease are young adults, teenagers and older children. Seasonal flu, in contrast, is usually far more severe in very young children, people over the age of 65 and people with chronic disease.

"We think this virus is initially amplifying among teenagers in schools and college students coming back from spring break and mixing," Schuchat said. It may move into other age groups later, she said.

Source : www.reuters.com

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A new way of the treating the flu

What happens if the next big influenza mutation proves resistant to the available anti-viral drugs? This question is presenting itself right now to scientists and health officials this week at the World Health Assembly in Geneva, Switzerland, as they continue to do battle with H1N1, the so-called swine flu, and prepare for the next iteration of the ever-changing flu virus.

Promising new research announced by Rensselaer Polytechnic Institute could provide an entirely new tool to combat the flu. The discovery is a one-two punch against the illness that targets the illness on two fronts, going one critical step further than any currently available flu drug.

"We have been fortunate with H1N1 because it has been responding well to available drugs. But if the virus mutates substantially, the currently available drugs might be ineffective because they only target one portion of the virus," said Robert Linhardt, the Ann and John H. Broadbent Jr. '59 Senior Constellation Professor of Biocatalysis and Metabolic Engineering at Rensselaer. "By targeting both portions of the virus, the H and the N, we can interfere with both the initial attachment to the cell that is being infected and the release of the budding virus from the cell that has been affected."

The findings of the team, which have broad implications for future flu drugs, will be featured on the cover of the June edition of European Journal of Organic Chemistry.

The influenza A virus is classified based on the form of two of its outer proteins, hemagglutinin (H) and neuraminidase (N). Each classification ? for example H5NI "bird flu" or H1N1 "swine flu" ? represents a different mutation of hemagglutinin and neuraminidase or H and N.

Flu drugs currently on the market target only the neuraminidase proteins, and disrupt the ability of the virus to escape an infected cell and move elsewhere to infect other healthy cells. The new process developed by Linhardt is already showing strong binding potential to hemagglutinin, which binds to sialic acid on the surface of a healthy cell, allowing the virus to entire the cell.

"We are seeing promising preliminary results that the chemistry of this approach will be effective in blocking the hemagglutinin portion of the disease that is currently not targeted by any drug on the market," he said.

In addition, Linhardt and his team have shown their compound to be just as effective at targeting neuraminidase as the most popular drugs on the market, according to Linhardt.

The approach can also be modified to specifically target the neuraminidase or the hemagglutinin, or both, depending on the type of mutation that is present in the current version of the flu, according to Linhardt.

In the next steps of his research, Linhardt will look at how their compounds bind to hemagglutinin, and he will test the ability to block the virus first in cell cultures and then in infected animal models.

"It is still early in the process," he said. "We are several steps away from a new drug, but this technique is allowing us to move very quickly in creating and testing these compounds."

The technique that Linhardt used is the increasingly popular technique of "click chemistry." Linhardt is among the first researchers in the world to utilize the technique to create new anti-viral agents. The process allows chemists to join small units of a substance together quickly to create a new, full substance.

In this case, Linhardt used the technique to quickly build a new derivative of sialic acid. Because it is chemically very similar to the sialic acid found on the surface of a cell, the virus could mistake the compound as the real sialic acid and bind to it instead of the cell, eliminating the connections to hemagglutinin and neuraminidase that are required for initial infection and spread of the infection in the body. The currently available drugs are translation-state inhibitors whose chemical structure allows them to only effectively target the neuraminidase.

Source : www.scienceblog.com

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