2009-10-02

In recent years, efforts to combat drug-resistant bacteria have focused on the immediate goal of reducing rates of hospital-acquired infections. But now global health officials face an approaching crisis: the number of different antibiotics available to treat such infections when they do occur is dwindling because pharmaceutical companies have neglected to invest in the development of new types of drugs.

Bacterial and parasitic diseases are the second leading cause of death worldwide, according to a report on antibiotic research released Sept. 17 by the London School of Economics and Political Science (LSE), with 175,000 deaths attributed to hospital-acquired infections each year in Europe alone. And because of the emergence of drug-resistant "superbugs," like Methicillin-resistant Staphylococcus aureus (MRSA), traditional antibiotics such as penicillin and its derivatives are becoming obsolete. New antibiotics are desperately needed, but the amount of money being spent on the research and development of these drugs is woefully inadequate. "The issue is quite dreadful," says Elias Mossialos, a professor of health policy at LSE and author of the report. "When you look down the pipeline, there are only a handful of new antibiotics in development, and all in the early stages."

There are several reasons why it's not cost-effective for the major pharmaceutical companies to invest more in antibiotic research, according to the report. The course of antibiotic treatment is typically short because the drugs help patients get better quickly, and doctors tend to curtail the number of prescriptions they write so as to avoid patients' developing resistance to the drugs. And when resistance to a certain antibiotic inevitably develops, the drug becomes largely obsolete.

But the report points out ways to incentivize pharmaceutical companies to invest more in antibiotic research. One solution would be for governments to offer drug companies an extension on patents for new antibiotics and perhaps even allow companies to transfer the extension to a different therapeutic category. This would help major pharmaceutical companies protect their monopolies on lucrative blockbuster drugs. (Many patents for high-earning drugs like Lipitor, a cholesterol-lowering medication worth $13 billion a year to Pfizer Inc., are due to expire in the next few years.) Governments could also offer companies rewards like vouchers for accelerated regulatory approval of new antibiotics. These, too, could be transferred internally to cover different drugs or even sold to other drug companies, the report said.

Such incentives, which health economists call pull mechanisms because they help pull a drug onto the market, would particularly help big drug companies, which have the capital to invest in early-stage research and development. For small- and medium-size biotech companies, which do not have the same abundance of capital, the report advocates more tax credits and government or NGO loans and grants to help support early-stage research and "push" new drugs onto the market. The LSE report recommends the European Union and the U.S. implement a hybrid of pull and push mechanisms to encourage antibiotic development, with bonus incentives linked to the drugs' efficacy.

Sweden, which took over the rotating presidency of the E.U. in July, is taking the lead on pushing for legislation on antibiotic development in Europe and the U.S. Otto Cars, head of the Swedish Strategic Programme Against Antibiotic Resistance, which advises the Swedish government, says Sweden will lobby for the E.U. to pass an incentives package for antibiotic research by the end of the year. Swedish leaders will also meet with U.S. officials in December to push for legislation there. "Physicians and the scientific community have been warning about this for years, but the political reaction has been very weak," Cars told TIME. "We are working to bridge the gap."

One of the few pharmaceutical companies concentrating on antibiotic development is Switzerland-based Basilea Pharmaceutica Ltd., which was founded in 2000 when Roche abandoned antibiotic development. Basilea recently began selling a new antibiotic called Ceftobiprole, which is effective against MRSA and other superbugs, in Canada, Ukraine and Switzerland. (It has submitted applications to market the drug in the U.S. and E.U. as well.) Basilea CEO Anthony Man says there is "no one-size-fits-all" incentive program to encourage companies to invest in antibiotic research. But he says major pharmaceutical companies and smaller, boutique firms both need to be lured back to the field.

"We simply do not have enough companies working on this area. There should be a basket of different solutions available from governments and NGOs that companies could choose from depending on the maturity of the R&D project in their pipeline," he says.

David Payne, head of GlaxoSmithKline's Antibacterial Discovery Performance Unit, says incentives would certainly help his research team, which is one of the few left in major pharmaceutical firms that continue to develop new classes of antibiotics. "A lot of people don't appreciate that in big companies it's a pretty competitive environment for funding for each of the therapeutic areas. Incentives would offer a way for us to accelerate our program and increase our probability of success."

But both Man and Payne also acknowledged that there are scientific obstacles to antibiotic research that cannot be solved by incentives alone. A deadly new class of antibiotic-resistant bacteria — so-called gram-negative bacteria — have a protective layer that has largely stymied drug developers. Drug-resistant bacteria "have multiple defense mechanisms to new drugs," says Man. "There are difficult technical challenges."

To Cars, the scientific challenges are more worrying than the financial obstacles. "Even if we got the incentives right, there's a knowledge gap that needs to be filled," he says. "The pharmaceutical companies have already picked the low-hanging fruit and developed drugs for the 'easy' bacteria. We are facing a rapidly spreading pandemic. And we are running out of ammunition. We need to do something now."

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