It's official: Project Bioshield is in tatters. Earlier this week the department of Health and Human Services canceled its contract with VaxGen to develop millions of doses of a next–generation anthrax vaccine. The cancellation came after repeated setbacks and acrimony between the company and the federal agency.
Federal health officials yesterday scuttled the largest piece of the Bush administration's two–year program to counter bioterrorism, canceling an $877.5 million contract with VaxGen to develop an anthrax vaccine after the company missed a deadline to begin human testing.
The decision, delivered in a one–page letter, ends a troubled effort by the small California firm that has come to symbolize the failures of the government's ambitious $5.6 billion Project BioShield. The termination occurred on the same day President Bush signed legislation attempting to salvage the program by reorganizing its management and pumping more money into firms doing the work.
"It's very disappointing that they took such aggressive and dramatic action without engaging in a discussion with us about potential ways for salvaging all the work that has gone into this program," said Lance Ignon, VaxGen's vice president of corporate affairs. "We believe there is a high probability that this technology would lead to a modern anthrax vaccine."
The company has spent more than $175 million of its own money on the project, its only current contract, he said.
The cancellation means the government will continue to depend on a controversial anthrax vaccine, used by the military and made by Emergent BioSolutions of Gaithersburg, years longer than expected. A spokesman for the Department of Health and Human Services said the agency remains committed to developing a next–generation anthrax vaccine but has not decided whether to hold another competition.
"We are moving as aggressively and quickly as we can to reach that goal," said Bill Hall, a department spokesman.
VaxGen was picked for the project in 2004 despite having never successfully produced a drug. It was known for a failed attempt at an AIDS vaccine, and the company has had accounting and management problems, which caused it be delisted from the Nasdaq Stock Market.
In signing on to develop an anthrax vaccine, the company agreed to meet the government's aggressive timetable, producing a drug in five years, half the industry standard for such a product. VaxGen was to be paid as it began delivering the 75 million doses to the government, enough for 25 million people, roughly the equivalent of the population in the New York and Washington areas combined.
The problems plaguing this program seem to be reflective of the fact that bioterrorism preparedness remains an unattractive field for the biggest and most sophisticated biotech and pharmaceutical companies. This leaves the government in the unenviable position of turning to small, untested companies to develop novel technologies and maneuver through the complex FDA approval process.
In the meantime, Congress and the Bush Administration is trying salvage the current model. The President recently signed the Pandemic and All–Hazards Preparedness Act, which creates a public–private partnership with the authority to issue preliminary research funding to small companies and universities for pre-clinical and early clinical research. It is hoped that this will help small companies maintain viability until they have products that are ready for government purchase. Still, we'll have to wait several years to see if this new approach pays off.
The many familiar over–the–counter (OTC) pain medicines that millions of consumers use every day can become surprisingly dangerous under the right (or wrong) circumstances. To help consumers understand these risks the FDA is proposing labeling changes for many OTC pain relievers, particularly for drugs containing acetaminophen.
The dangers of over–the–counter painkillers will be prominently highlighted on the labels of hundreds of common remedies under a proposal announced yesterday by the Food and Drug Administration.
The proposed warnings—about possible liver failure from acetaminophen and gastrointestinal bleeding from other medicines like aspirin, ibuprofen, naproxen and ketoprofen—follow alarms about overusing such medications.
"These drugs are used by tens of millions of people every week, and they are quite safe," Dr. Charles Ganley, director of the F.D.A. office of nonprescription drugs, said in a news conference.
But Dr. Ganley said that when the drugs are used by so many people rare problems could add up. Doctors have raised concerns about overdoses from drugs containing acetaminophen, a leading cause of acute liver failure.
More than 200 million Americans a year take products like Tylenol with acetaminophen, and overdoses cause up to 450 deaths a year from acute liver failure.
Suicides account for most of the deaths, but up to 200 occur when patients unknowingly take too much or combine multiple medications that include the drug, according to statistics presented to the drug agency.
"People will take a medicine to go to sleep at night and they'll take a cold medicine and they'll take a medicine for their joint pains, and they won't realize that each of one of those products contains, say, acetaminophen," said Dr. Paul B. Watkins, a professor of medicine at the University of North Carolina at Chapel Hill. "They are unknowingly taking four times the maximum daily dose of acetaminophen."
The proposed rules would mean that any of the hundreds of over–the–counter products with acetaminophen would have to list it prominently on the principal display panel of the container and the outer carton. The containers would include a prominent warning that acetaminophen overdoses can cause liver failure and that the drug should not be used by people drinking three or more alcoholic drinks.
Separately, products containing aspirin and other painkillers known as nonsteroidal anti–inflammatories like ibuprofen, ketoprofen and naproxen will warn of gastrointestinal bleeding. One study found 15 deaths as a result of gastrointestinal bleeding for each 100,000 users of the medications, also known as NSAIDs.
The Government Accountability Office (GAO) recently released a report that found that the pharmaceutical industry is spending ever larger sums of money on the research and development of new medicines, but fewer new drugs are coming on the market. The billion–dollar question, however, is what to make of these findings.
Drug companies are becoming less innovative, with the number of new drugs being developed failing to keep pace with the substantial increases in spending on research and development, according to congressional investigators.
A report released yesterday by the Government Accountability Office, the investigative arm of Congress, found that annual research and development spending by the pharmaceutical industry increased 147 percent, to $60 billion, between 1993 and 2004. At the same time, the number of new drug applications to the Food and Drug Administration grew by only 38 percent, and it generally has declined since 1999.
What is more, about two–thirds of the new applications were for drugs that simply represent modifications to existing medicines, while 32 percent were for potentially innovative new drugs.
"Over the past several years it has become widely recognized throughout the industry that the productivity of its research and development expenditures has been declining," investigators wrote in the 52–page report. "That is, the number of new drugs being produced has generally declined while research and development expenditures have been steadily increasing."
There are several reasons for the decline, investigators said, including a growing difficulty in translating basic research into effective medicines; a shortage of physician–scientists who have both medical and research expertise; and a bigger emphasis on developing "blockbuster" drugs that bring in the most money, which has reduced the numbers and types of new drugs. The industry also increasingly has been trying to develop treatments for complex diseases such as cancer, resulting in higher failure rates.
Three Democratic lawmakers who requested the report—Rep. Henry A. Waxman (Calif.) and Sens. Richard J. Durbin (Ill.) and Edward M. Kennedy (Mass.)—said it shows that the drug development system should be reexamined.
"The findings... raise serious questions about the pharmaceutical industry claims that there is a connection between new drug development and the soaring price of drugs already on the market," Durbin said in a statement. "Most troubling is the notion that pharmaceutical industry profits are coming at the expense of consumers in the form of higher prices and fewer new drugs."
We find it likely that the industry is actually becoming more innovative, rather than less. By pursuing novel drug targets the industry is bumping up against more unforeseen side effects (like Vioxx) and running into more late-stage clinical trial failures (like torcetrapib). Over the past 30 years, the industry has been tremendously productive, and the “low-hanging fruit” has already been plucked. As companies push the boundaries of known science, high-profile failures are bound to crop up.
As for complaining about blockbuster drugs, the industry has to recoup its enormous R&D costs and still earn a healthy profit. And this naturally leads the industry towards the development of drugs for chronic illnesses like heart disease, cancer, and diabetes. And many drugs for these conditions replace more expensive forms of hospital and physician care.
Lately, the biotech industry seems to have a better track record when it comes to innovation. But this has to be taken with a grain of salt as well, given the billions of dollars in funding that Big Pharma pumps into small biotech companies.
More troubling than the GAO's findings (which are unsurprising) is the political climate in Congress, which seems eager to add new regulations to what is easily the most heavily regulated industry in the world. This will dampen innovation and drive up costs even further, exacerbating the very problems Congress is trying to solve.