Creating Incentives and Changing Policies
Moreover, drug development has become hugely expensive, with the direct and indirect costs to bring a drug to market now averaging more than $800 million.
We need both legislative and FDA-initiated remedies. In 2005, Senators Joe Lieberman (D-CT) and Orrin Hatch (R-UT) introduced BioShield II, legislation that, if enacted, would have created tax incentives for companies that develop new antibiotics and would limit their liability for side effects, as has been done for vaccines. It would also have extended patents on antibiotics to compensate for time lost while awaiting FDA approval.
The bill’s most controversial provision was wild-card exclusivity, which would have allowed a drug company that markets a new antibiotic to extend the patent on any product in its portfolio by up to two years with the approval of federal officials. If Pfizer (www.pfizer.com) were to discover a new antibiotic, for example, the company might be granted more time to market Viagra before generic manufacturers were permitted to produce that drug.
Although the wild-card idea offers the best hope of fostering antibiotics research, it was a little too wild in its proposed form. It would have permitted federal officials to grant a wild-card patent extension whenever a pharmaceutical maker developed an antibiotic that met the FDA’s broad definition of a new chemical entity. Under this language, if Bayer (www.bayer.com) were to chemically alter its already marketed antibiotic ciprofloxacin (Cipro), for example, the company might qualify for a lucrative patent extension on Levitra, even if the new antibiotic wasn’t significantly better than its precursor.
A more appropriate standard would be that in order to qualify for wild-card exclusivity, a drug company’s new antibiotic would have to meet FDA’s criteria for fast-track designation during developmenta product that is intended for the treatment of a serious or life-threatening condition and demonstrates the potential to address unmet medical needs. Thus, a new antibiotic would qualify if it were intended for serious infections and if it were active against bacteria widely resistant to existing antibiotics, if it were more easily administered, or had fewer side effects than alternatives.
If we are to stimulate the development of new antibiotics, other aspects of public policy need attention as well. It has been said that when the FDA sneezes, the pharmaceutical industry gets pneumonia. A chilling example is the delay of an injectable antibiotic called Tigecycline for infections caused by antibiotic-resistant pathogens. Its manufacturer, Wyeth-Ayerst Laboratories, had done two human studies to show that the drug was safe and effective and was planning a third and final one.
In 2000, however, the FDA changed the rules for measuring efficacy in antibiotics’ trials, which required the company to double the number of patients in the trials from 4,000 to 8,000. That made the investment required by Wyeth much greater in both time and money. The drug finally was approved in 2005.
This kind of policy decision has a pernicious ripple effect. As a result [of FDA’s change in policy], we’ve got fewer companies involved in the antibiotic discovery business at a time when antibiotic resistance to existing drugs is becoming more of a problem, according to Robert C. Moellering, Jr., M.D., chairman of the department of medicine at Beth Israel Deaconness Medical Center in Boston.
We need also to adopt the kinds of critical FDA reforms suggested by the Infectious Diseases Society of America. Among them are expediting the publication of updated guidelines for clinical trials of antibiotics, including a clear definition of what constitutes acceptable surrogate markers as endpoints; encouraging imaginative clinical trial designs that lead to a better understanding of antibiotics’ efficacy; the exploration of animal models of infection, in vitro technologies, and microbiologic surrogate markers to reduce the number of efficacy studies required; and the FDA’s granting of accelerated review status to priority antibiotics.
The two novel antibiotics introduced since 2000 won’t be enough to keep rapidly mutating pathogens at bay for long, and once resistance appears, it will spread rapidly. Unless we create economic and regulatory incentives for companies to develop antibiotics, it’s unlikely that we’ll see many more wonder drugs in the near future. That’s something to think about next time you contract bronchitis or are hospitalized with a flesh-eating bacterial infection.