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WASHINGTON, Oct 26, 2004 (United Press International via COMTEX) -- The flu vaccine shortage now facing the United States could be duplicated in an antibiotics shortage in the future. The current situation painfully demonstrates what happens when the number of drugmakers producing a vaccine drops from more than a half dozen in the 1970s to just two -- and really only one active manufacturer, Aventis Pasteur -- today.
S. James Matthews, associate professor of clinical pharmacy at Northeastern University in Boston, told UPI's HealthBiz that of 506 drugs in the research and development pipeline, only five are new antibiotics.
"We could envision in the future a time where we have an organism and we don't have a drug to treat it," Matthews said. "This is frightening. This is worse than any bioterror attack because this would be something that would affect thousands and thousands of people just in the United States, with the ramifications of not being able to treat the patients ... and they're not going to make it."
The loss of antibiotic drugs to resistance is a well-known issue, but it represents just part of the problem and risk for pharmaceutical companies that want to get the longest possible patent-protected use for a drug to recoup what could be a decade of R&D and $1 billion in costs.
Antibiotics, somewhat like vaccines, are short-use medications, typically requiring only a week or two of treatment, either alone or in combination with other drugs. They are not the moneymakers that hypertension drugs or cholesterol-lowering statins, which are used long-term, would be. It's also a well-used pipeline -- much of what is new really is a remix and update of what already has been available.
"It's probably a fair statement to say that over time -- over the past few years -- the bigger companies probably have reduced their activity with regard to antibacterial drug development," Dr. Mark Goldberger, of the Food and Drug Administration's Center for Drug Evaluation and Research, told HealthBiz. "I think a lot of that decision-making is related to the particular economics of antibacterial drugs."
Goldberger added, however, for the great majority of patients today, there are adequate antibiotics available.
"As we move forward, the likelihood of some problems coming up is likely to increase," he said. "The problem is you don't get a brand new antibacterial overnight. If you think there is going to be a problem five years down the road you have to be working very actively now to have products five years down the road."
Goldberger said the situation makes him and others in the field nervous. "Not that there is an acute issue now, (but) the trends are not necessarily favorable," he said.
Many larger drugmakers have turned over antibacterial R&D to smaller companies, which Goldberger said have run into problems because of the expertise required in developing molecules combined with the timeline for development and the huge cost.
"In the long run ... fundamental drug decisions will come from larger companies and they are under pressure to maximize revenues," he said.
One big drugmaker, Wyeth, still investigates antibacterials. Dr. Evan Loh, a company vice president who oversees the clinical infectious-disease pipeline, said the company "has made a big commitment to provide agents that will be able to hopefully fight these superbugs currently being written about."
Wyeth's latest offering is tigecycline, for treating complicated skin infections. It represents a small, antibacterial niche with the potential for stronger sales. Loh said the company is optimistic its indications can be expanded and it hopes to seek an FDA new drug application by the end of the year.
Tigecycline did not happen overnight, however, it was discovered in 1991 and its approval is tentatively slated for 2006-2007, which means any antibiotic shortage problem predicted today might not have a solution for a decade or more.
"There are barriers in the sense that today's regulatory environment requires a higher level of scrutiny (for safety and efficacy)," Loh said.
He added there also are R&D challenges involving contracts with company drug investigators, "so that all of them understand who is responsible for what," and everyone has appropriate coverage and support for clinical trials -- the cost of which often are borne by the pharmaceutical company.
"My hope is that we will have enough companies (doing antibiotic research) in the future," he said. "More companies in the mix pushes innovation, pushes creativity, and pushes timelines."
In an editorial last week in the journal Nature, Dr. Carl Nathan, of Weill Cornell Medical College in New York City, wrote of the need for the United States to look carefully at the lessons of the flu vaccine shortage and then strike a new approach to basic antibacterial research. He said there is much common ground between scientists who are worried about drug resistance -- and who have attracted more public attention because they fear a return of many diseases long-ago eradicated in the United States -- and health officials who are struggling to find enough antibiotics to treat those same types of infections in developing nations.
Those fighting antibiotic resistance "will demand that there be a solution," he said. "The diseases of poor countries at any moment can be in the rich countries. We risk returning to a time we thought we put behind us."
The question then becomes how to get Big Pharma back in the antibiotic hunt.
Nathan proposed a new player in the game -- a not-for-profit drug company that would focus on identifying and developing new molecules. The group would license its intellectual property free to any company that commits to producing the drug to serve the needs of patients and society.
"My real goal is to get people to recognize that we have a huge problem," Nathan told HealthBiz. "It's not good enough to sit and wait, like with the flu vaccine. The same thing is going to happen, but I think it could be even more devastating with regard to antibiotics."
Nathan said investors do not realize they actually are making medical policy by putting such stringent financial pressures on pharmaceutical companies and must change what is an acceptable return on investment. He said drug companies should move away from broad-spectrum antibiotics and focus on more specific antibiotics that will not soon become resistant because they have limited use.
Goldberger acknowledged ideas such as those of Nathan and others are worth discussing, but said the bottom line is that the government does not have the resources to fund the long-term R&D needed to bring new antibacterials to market.
The Infectious Diseases Society of America, in Alexandria, Va., is pushing for the government instead to support legislation commonly called "Bioshield II." It builds on the Project Bioshield legislation signed into law last July to encourage development of treatments for a stockpile of drugs in case a bioterrorism response is needed.
"We pressed for that to be expanded to include antibiotics, but that was not accepted," Robert J. Guidos, IDSA's director of policy and government relations, told HealthBiz. "Since the Bush administration first announced Bioshield I in February 2003, no Americans have died as a result of bioterrorism, but tens of thousands have died as a result of antibiotic-resistant organisms and influenza. Don't we need to fix that problem?"
IDSA also said other incentives should be considered -- tax credits, strengthened intellectual property rights, liability protections and a federally guaranteed purchase program. Guidos said IDSA spoke with 10 drug and biotech companies and asked them about incentives they thought would work and got a varied response, depending on the size of the company.
Large companies, he said, could use the tax credits but small companies do not have the income to make credits worthwhile.
"Uniformly we heard there was a need for FDA to re-think the way they do some requirements to prove these products are safe and effective," he said.
Goldberger said FDA has been trying to "develop a paradigm" to help companies research and develop antibacterials in a more timely and cost-efficient manner, but he added the trade-off always is in the quality of the data.
"There is a relationship between data and how comfortable you feel with conclusions you draw from it -- efficacy and safety," he said, "so be careful of those trade-offs."
There may not be an antibiotic crisis at the moment -- the problem is getting industry and government to act as though one is occurring, but long enough before it really happens, to assure a solution.
Copyright 2004 by United Press International.