With news that migratory birds could carry avian flu to the United States sometime this spring, people across the nation have stepped up their worrying. And scientists have stepped up their efforts. Companies are scrambling to develop tests, drugs and vaccines to detect, treat and prevent human cases and head off the potential for a pandemic.
Just how hopeful are drug makers that such products will turn into blockbusters, simultaneously making their mark on the virus and company cash flow?
Consider this: Though pandemic flu is a fear rather than a certainty — unlike, say, heart disease, which is the leading killer in the United States — AVI BioPharma, a Portland, Ore., biopharmaceutical company, has sold off most of its cardiac drug business to concentrate on infectious disease drugs, notably treatments for pandemic flu. That, despite the fact that the company filed only in March with the Food and Drug Administration to begin testing its leading avian flu drug candidate in humans.
AVI BioPharma’s business strategy — betting the farm on a product largely of use only if, and it’s a big if, the H5N1 virus moves significantly from birds to humans — is actually a growing phenomenon. More and more companies, and investors, are putting up cash, and hope, that a growing list of products will be the ones to turn H5N1 into a preventable or treatable illness.
Kleiner Perkins Caufield and Byers, for example, a highly regarded venture capital firm in Menlo Park, Calif., announced its $200 million Pandemic and Bio Defense Fund earlier this year, with money earmarked for products aimed at detecting, preventing and treating "global pathogenic infectious diseases."
And in early April, the avian flu index on 19 products tracked by the investment strategy firm TrendMacrolytics, also based in Menlo Park, was up 12 percent over the month before. The S&P 500 index was up only 1 percent for the same time period.
Most of the companies now working on diagnostic tests, vaccines and drugs for avian flu have had at least prototype products in their pipeline for years. But Donald Luskin, TrendMacrolytics’ chief investment officer, says three things have heated up the scientific fervor over a possible pandemic in just the last few months: embarrassment of the Bush administration over its Hurricane Katrina response, resulting in a massive effort to inform the public about pandemic flu; the recent spread of avian flu to developed countries including Israel, Turkey and Scotland; and the fact that scientists now know that avian flu is likely being spread by migratory birds "which means that by the end of 2006 there will be avian flu in birds on every continent."
Science still preliminary
At this point, however, experts think the science is impressive but still very preliminary.
So far, only one new drug for avian flu, Peramivir, made by BioCryst of Birmingham, Ala., has started U.S. human clinical trials, says John McCamant of the Medical Technology Stock Letter.
Peramivir is a neuraminidase inhibitor, which means it is in the same drug class as Tamiflu and Relenza, both of which are already approved to prevent and treat influenza. But Tamiflu may not be effective against all strains of the bird flu virus, and Relenza, an inhaled drug, may not be effective for people with chronic lung problems and in people whose lungs are impacted by the virus.
In its oral form, Peramivir did not prove to be effective, but the company is now testing it in injectable form, which did seem to work in animal studies.
While BioCryst and its investors are hopeful about the potential effectiveness of injectable Peramivir, Klaus Stohr, head of the World Health Organization’s pandemic flu effort, reminded a group of scientists gathered for a sobering meeting on pandemic flu vaccines at Cleveland’s Case Western Reserve University in early April that there is no evidence yet that neuraminidase inhibitors reduce deaths from pandemic flu.
The vaccine conference was sobering because the group, gathered together to learn about novel pandemic flu vaccine approaches, took place just a couple of weeks after the New England Journal of Medicine published a study confirming what was already suspected — the current stockpiled vaccine against avian flu made by sanofi pasteur, one of two companies with a government contract for pandemic flu vaccine, only generates an immune response at a dose of 90 micrograms, or 12 times the dose needed for the annual seasonal flu vaccine. If the dose needed per person can’t be decreased, the current U.S. stockpile only has enough vaccine for 4 million people.
But new technological ideas for avian flu abound. "I’m often struck by the innovation that comes out of crisis," says Dr. Bruce Gellin, head of the U.S. government’s Vaccine Program Office.
Dr. Anthony Fauci, head of the National Institute of Allergy and Infectious Diseases (NIAID), which is handing out the bulk of government funding for avian flu research, counts about 30 companies now testing vaccines for pandemic flu.
According to research by Griffin Securities of New York City, MedImmune, a firm in Gaithersburg, Md., is investigating 16 nasal spray versions of an avian flu vaccine, one for each variation of the hemagglutinin protein — the H in H5N1. The H can change over time, rendering developed vaccines insufficient or ineffective, so an armamentarium could be an important approach.
And Novavax of Malvern, Pa., has a "virus-like particle" technology which could allow the company’s vaccine to mimic the virus to create an immune response rather than having to actually inject bits of the virus, as is usually done.
While information on vaccines in development will be front and center at three World Health Organization meetings in Geneva at the end of April and early in May, Arthur Heuer, a professor of engineering at Case Western, who chaired this month’s vaccine conference, acknowledged that it will be years before we know whether the new vaccine ideas are effective.
Working with what’s available now
Should a pandemic not wait, one approach may be to increase the immune response of the vaccines now in the stockpile, using products called adjuvants, or additives.
Alum is the only adjuvant currently approved by the Food and Drug Administration, but it provides a fairly weak response, say experts, and adjuvants are difficult to develop and require human trials for approval. A novel adjuvant in development by Chiron, a vaccine firm recently purchased by Novartis, has shown immune response when combined with an experimental avian flu vaccine. GlaxoSmithKline also is working on a novel adjuvant, and Hemispherx Biopharma of Philadelphia is testing an adjuvant that could boost the effectiveness of both antiviral drugs and vaccines.
If pandemic flu strikes the globe in the next year or two, researchers such as Anne Moscona, an associate professor of medicine at the Weill Cornell Medical School in New York City, who has published several articles in the last few months on treating pandemic flu, says our best hope would still be the older approaches — quarantine, the neuraminidase drugs and use of the small amount of stockpiled vaccines.
But even with the possibility of a sudden pandemic, key scientists say the flurry of current research — even though products could be years away — is absolutely worthwhile.
Why? Because we should have been doing it all along. Most avian flu conferences, and there are some held each week, start with admonishment for global health officials and private industry for not ensuring greater vaccine manufacturing capacity around the world and for not beginning drug and vaccine research, and stockpiling, years or even decades sooner.
Whether a pandemic hits in the next year or two, another one is likely to be along sometime in the future, and researchers say the current effort can only improve the sad state of scientific preparedness we’re in now.
Toward that end, serious scientists applaud the growing variety of approaches.
"The beauty of science is [most apparent] when you have multiple, individual initiatives going on by creative people," says Fauci of NIAID. "At the end of the day, you get the best science out of it."
Fran Kritz is a freelance writer based in the Washington, D.C., area.