"The policy and execution of the policy by regulatory authorities really matter in terms of how drugs are developed and even
what drugs we attempt to develop in the first place," says Steve Projan, vice president of biological technologies, Wyeth
Research. "The regulatory authorities have become very gun-shy, and their response is larger trials to assess the safety of
drugs. But there are only a certain number of 20,000-patient trials we can run until we run out of money."
Projan says new trial-design requirements for antibiotics dangerously limit the number of potential players. He is calling
for provisional FDA approval of antibiotics based on Phase II data, followed by rigorous Phase IV monitoring. "That way, we
get the large safety datasets that we need to assess the safety of drugs, but we do it in a manner in which we don't have
to sell the farm and mortgage the house to pay for the large trials that are currently demanded," he says.
Others say the need for new antibiotics is too important for FDA to pursue its current course for long. "As the medical need,
such as MRSA, becomes even more self-evident, then the regulatory environment will become more balanced," says Susan Froshauer,
CEO of Rib-X Pharmaceuticals, a start-up focused on next-generation antibiotics.
Today's Market: No "International Machinery"
Augmentin. Zithromax. Cipro. These are just some of the blockbuster brands that have reached the end of their patent life
in recent years. By the time J&J's juggernaut drug Levaquin goes off patent in 2011, Big Pharma will have effectively exited
the business of broad-spectrum antibiotics for community-acquired infections.
At first glance, these massive patent expirations may seem to be a good thing for the developing world. "When Cipro went off
patent, the cost went down to nominal unit prices, and Asia-based companies began shipping Cipro out by the crateload," says
Jonathan Angell, an infectious-diseases analyst at Datamonitor. "And with more patent expiries en route, like Avelox, Zyvox,
and Levaquin, there will be another generation of generic drugs that are available."
In the face of massive genericization of broad-spectrum antibiotics, pharma has turned its attention to the high-value hospital
market. (Meanwhile, generic arms of companies like Sandoz and Greenstone remain profitable in this area.) These hospital-administered
therapies serve niche indications, but they can cost "an arm and a leg," says Datamonitor's Angell. Among the drugs anticipated
are Pfizer's Zeven, Theravance's telavancin, Cerexa's ceftaroline, and J&J's ceftobiprole. (See "Antibiotic Pipeline," .)
Additional specialization is likely to occur. By 2016, newly launched drugs will account for only 1 percent of the volume
of antibiotics sold in the seven major markets and 23 percent (or $2 billion) of the value, according to Datamonitor.
These late-stage antibiotics will mostly compete with already established products. There is also likely to be a glut of new
drugs targeted at specific infections, namely complicated skin and soft-tissue infections and pneumonias. That means the antibiotic
market will be characterized by both intense competition and massive unmet medical need—particularly to manage infections
caused by strains of pseudomonas or acinetobacter (now seen in soldiers returning from Iraq), or other new strains of bacteria
that may arise.
"The development of all drugs takes 10 years—and it's difficult to predict what the big outbreaks are going to be and what
drug resistance is going to be," says Barry Eisenstein, MD, senior vice president, scientific affairs, for Cubist Pharmaceuticals.
The company markets Cubicin, a once-daily IV bactericidal antibiotic that treats vancomycin-resistant enterococci and MRSA.
"That's nature and evolution. We can make some reasonable predictions, but it's not like knowing that diabetes is still going
to be problem five years from now."