[e-drug] bad bugs, no drugs

["E-Drug" <e-drug@healthnet.org>]

E-DRUG: bad bugs, no drugs
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[A "superbug" crisis is looming, with no "Superdrugs" in sight. And Superman has also died...
Copied as fair use, from Lancet Infectious Diseases (well worth the read!
Also, the exec summary of the report. 
The full paper is at http://www.idsociety.org/Template.cfm?Section=Antimicrobials&Template=/ContentManagement/ContentDisplay.cfm&ContentID=9718
[repair URL!] WB]

http://infection.thelancet.com/journal/vol4/iss9/full/laid.4.9.newsdesk.30545.1

IDSA warns of looming superbug crisis
Marilynn Larkin 

A stagnant antibiotic pipeline bodes ill for public health, warns the Infectious Disease Society of America (IDSA) in its latest report.

Our issue isn't with viruses or bioterrorism agents; it's with the everyday bacterial infections such as staphylococcus and Escherichia coli that are always with us, says David Gilbert (Oregon Health and Science University, Portland, OR, USA).

These infections generally are not fashionable or trendy enough to hit the newspapers with the regularity of SARS or smallpox. But to me, their presence is like 9/11, said Gilbert, an ex-president of IDSA and a member of the society's taskforce on antimicrobial availability, which helped to prepare the report.

The difference is that on 9/11, the planes hit the buildings, and now we're trying to figure out in retrospect what to do about it. But [with resistant bacterial infections] we can see the planes coming from far away. If we're smart, we have many opportunities to take care of this issue. But so far, we're not being smart about it.

Drug companies want incentives such as tax write-offs early on, during the discovery and development phase of research, rather than at the end of a 17-year process that ends with a marketable drug, Gilbert explains. However, policymakers resist, citing concerns that companies are already making enough money, or that new drugs will be expensive.

This disconnect is a major hurdle, asserts Gilbert. It's the short-term vision versus the long-term vision. If we don't develop new drugs, within a few years, we're going to have hospitals filled with patients with resistant infections. So we have to convince at least some members of congress to take a longer view of the situation. Sometimes it's okay to let the drug companies make a profit because in the long term, you end up saving society money.

The IDSA report, Bad bugs, no drugs (http://www.idsociety.org ) proposes several policy and administrative actions that could help avert a superbug crisis: establishing an independent commission to prioritise antimicrobial discovery, which would decide which infectious pathogens to target, using appropriate incentives; creating a wild-card patent extension in which a company that develops and receives approval for a priority antibiotic could extend the market exclusivity period of another FDA-approved drug, as long as the company commits to investing a portion of the profits derived during the extension period back into antibiotic R&D; providing tax incentives for priority antibiotic R&D; and establishing measured liability protections, similar to those that exist for childhood vaccines.

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http://www.idsociety.org/Template.cfm?Section=Antimicrobials&Template=/ContentManagement/ContentDisplay.cfm&ContentID=9770

Bad Bugs, No Drugs Executive Summary

Antibiotic-Resistant Bacterial Pathogens: Why We Are Concerned
Antibiotics and other antimicrobial drugs have saved millions of lives and eased patients suffering. Although they have been dubbed miracle drugs, antibiotics are not always effective. Over time, bacteria can develop resistance to existing drugs, making infections difficult if not impossible to treat.

A multi-pronged approach is needed to limit the impact of antibiotic resistance on patients and the public. These efforts include educating physicians, patients, and parents about the appropriate use of antibiotics, developing and applying infection control and immunization policies and practices to prevent transmission, surveying clinical and prescription data, and developing safer alternatives to antibiotic uses in agriculture.

The purpose of this document, however, is to call attention to a frightening twist in the antibiotic resistance problem that has not received adequate attention from federal policymakers: The pharmaceutical pipeline for new antibiotics is drying up.

Until recently, research and development (R&D) efforts have provided new drugs in time to treat bacteria that became resistant to older antibiotics. That is no longer the case. Unfortunately, both the public and private sectors appear to have been lulled into a false sense of security based on past successes. The potential crisis at hand is the result of a marked decrease in industry R&D, government inaction, and the increasing prevalence of resistant bacteria. Infectious diseases physicians are alarmed by the prospect that effective antibiotics may not be available to treat seriously ill patients in the near future.

Why Policymakers Should be Concerned Too
Policymakers already have recognized the urgent need to spur R&D related to biodefense. While this concern is appropriate, it is important to keep things in perspective. There has not been a single case of smallpox anywhere on the planet since the 1970s, but drug-resistant bacterial infections kill tens of thousands of Americans every year, and an epidemic could harm millions.

Why should policymakers care about antibiotic resistance and the lack of new antibiotics to treat resistant infections?

Infections caused by resistant bacteria can strike anyonethe young and the old, the healthy and the chronically ill. Antibiotic resistance is a particularly serious problem for patients whose immune systems are compromised, such as people with HIV/AIDS and patients in critical care units. 
About 2 million people acquire bacterial infections in U.S. hospitals each year, and 90,000 die as a result. About 70 percent of those infections are resistant to at least one drug. The trends toward increasing numbers of infection and increasing drug resistance show no sign of abating. 
Resistant pathogens lead to higher health care costs because they often require more expensive drugs and extended hospital stays. The total cost to U.S. society is nearly $5 billion annually. 
The pipeline of new antibiotics is drying up. Major pharmaceutical companies are losing interest in the antibiotics market because these drugs simply are not as profitable as drugs that treat chronic (long-term) conditions and lifestyle issues. 
Drug R&D is expensive, risky, and time-consuming. An aggressive R&D program initiated today would likely require 10 or more years and an investment of $800 million to $1.7 billion to bring a new drug to market. 
Resistant bacterial infections are not only a public health problem; they have national and global security implications as well. 
The Institute of Medicine and federal officials have identified antibiotic resistance and the dearth of antibiotic R&D as increasing threats to U.S. public health. 
IDSAs Investigation
IDSA has investigated the decline in new antibiotic R&D for more than a year, interviewing stakeholders from all sectors. Society leaders have met with officials from the Food and Drug Administration (FDA), the National Institute of Allergy and Infectious Diseases (NIAID), the Centers for Disease Control and Prevention (CDC), congressional members and staff, executives from leading pharmaceutical and biotechnology companies, representatives from public-private partnerships that are focused on infectious diseases-related product development, patients, and other stakeholders. Each stakeholder has an important role in furthering future antibiotic discovery and development and limiting the impact of antibiotic resistance. However, based upon past successes, the pharmaceutical and biotechnology industries are clearly best situated to take the lead in developing the new antibiotics needed to treat bacterial diseases. As such, industry action must become the central focus of an innovative federal public health effort designed to stimulate antibiotic R&D. 

IDSAs investigation has revealed that the incentives most likely to spur R&D within major pharmaceutical companies include those that provide financial benefits prior to a drugs approval (e.g., tax credits for R&D), commence at the time of approval (e.g., wild-card patent extension), reduce the costs of clinical trials (e.g., FDA flexibility concerning the evidence necessary to demonstrate safety and efficacy; NIAID-sponsored research to develop rapid diagnostics tests, etc.), and reduce companies risks (e.g., liability protections). R&D at smaller biotechnology companies also could be stimulated through statutory and administrative changes. Finally, new funding for critical federal public health programs, and public and private research efforts, would help to ensure progress as well as limit the public health impact of antibiotic resistance. 

Following is a list of specific potential legislative solutions, administrative recommendations, and funding requests:

Potential Legislative Solutions To Fuel Innovation
Congress and the Administration must work together to enact statutory incentives that stimulate the discovery and development of new antibiotics to treat drug-resistant and other dangerous infections. Critical priority incentives that will have the greatest impact are indicated.

Commission to Prioritize Antimicrobial Discovery  [CRITICAL PRIORITY]
Establish and empower an independent Commission to Prioritize Antimicrobial
Discovery to decide which infectious pathogens to target using these legislative R&D incentives and administrative solutions: 

Supplemental intellectual property protections:
Wild-card patent extension. [CRITICAL PRIORITY] 
A company that develops and receives approval for a priority antibiotic could extend the market exclusivity period of another FDA-approved drug as long as the company commits to invest a portion of the profits derived during the extension period back into antibiotic R&D. 
Restoration of all patent time lost during FDA's review of priority antibiotics 
Extended market exclusivity similar to what has been successfully implemented for pediatric and orphan drugs 
Other potential statutory incentives:
Tax incentives for R&D of priority antibiotics [CRITICAL PRIORITY] 
Measured liability protections 
Additional statutory flexibility at FDA regarding approval of antibiotics, as needed 
Antitrust exemptions for certain company communications 
A guaranteed market 

In 2002, out of 89 new drugs, no new antibiotics were approved.
 
Establish similar statutory incentives to spur R&D for rapid diagnostic tests for targeted pathogens, which will help to reduce the cost of clinical trials  

Potential statutory incentives of interest to small biopharmaceutical companies:
Waive FDA supplemental application user fees for priority antibiotics 
Tax credits specifically targeting this segment of the industry 
Small business grants 
In addition to enacting statutory incentives to spur antibiotic R&D, Congress should work with the Administration to implement administrative recommendations at FDA and NIAID. 

Food and Drug Administration Recommendations
FDA is a pivotal and constructive partner in the process of antibiotic development. In order to effectively implement FDAs plan, Innovation or Stagnation: Challenge and Opportunity on the Critical Path to New Medical Products, modifications to existing policy, procedures, and guidelines are necessary. Each of the following recommendations is a critical priority: [CRITICAL PRIORITIES]

Accelerate the publication of updated guidelines for antibiotic clinical trials to provide needed clarity, and revisit existing guidelines as appropriate to ensure their relevance 
Encourage imaginative clinical trial designs that lead to a better understanding of drug efficacy against resistant bacterial pathogens 
Provide a clear definition of acceptable surrogate markers as end points for clinical trials of bacterial infections 
Explore and, when appropriate, encourage the use of animal models of infection, in vitro technologies, and valid microbiologic surrogate markers to reduce the number of efficacy studies required for each additional indication while maintaining safe and effective drug dose regimens 
Explore with NIAID all opportunities to streamline antibiotic drug development 
Grant priority antibiotics accelerated review status 
National Institute of Allergy and Infectious Diseases Recommendations
NIAID could play a central role in the R&D process. To do so, NIAID should implement the following recommendations. Each is a critical priority: [CRITICAL PRIORITIES]

Aggressively encourage translational (bench to bedside) research as described in NIHs Roadmap for Medical Research 
Remove roadblocks to antibiotic R&D that may exist in NIAIDs structure and guidelines, including any unnecessary restrictions affecting companies intellectual property rights 
Increase the number and size of grants that support discovery of new drugs that treat targeted pathogens 
Develop and expand collaborations with industry and the infectious diseases research community 
Sufficiently fund and rapidly launch NIAIDs newly established Drug Discovery and Mechanisms of Antimicrobial Resistance Study Section 
Engage outside experts in research planning and ensure more transparent decision-making 
Explore with FDA all opportunities to streamline antibiotic drug development 
Encourage research on topics directly related to conduct of clinical trials 
Sponsor research into new rapid diagnostic tests for bacterial infections that, when available, could reduce the cost of clinical trials 
Encourage research on antibiotic use and resistance development 
Fund placebo-controlled trials to evaluate the necessity of antibiotic therapy for selected diseases  
New Funding Needed
The increasing threat of drug resistance, concomitant with decreasing antibiotic R&D, requires a dramatic increase in public funding for CDC, FDA, NIAID, and public-private research efforts. At a minimum, Congress and the Administration must work together to invest new resources (i.e., not shift funds from other public health efforts) into the following critical program areas:

Double CDC's antimicrobial resistance program funding to $50 million in 2005 and continue to increase it by $25 million increments until 2009 to a total of $150 million 
Increase FDAs funding by $25 million to support implementation of the Critical Path plan (which would help decrease the cost of antibiotic development), the development of new antibiotic guidelines, and to speed antibiotic reviews 
Significantly increase NIAIDs translational and antibiotic resistance research efforts 
Support synergistic public/private partnerships that focus on infectious diseases medicines 
Conclusion
Without innovative public policy and additional financial support, fewer and fewer antibiotics will be available to treat the increasing number of drug-resistant and dangerous microbes that threaten Americans and the global community. The proposals advanced in this document are intended to ensure a sustainable supply of safe and effective antibiotics to protect the publics health.

We urge policymakers to act quickly.

Full report at http://www.idsociety.org/Template.cfm?Section=Antimicrobials&Template=/ContentManagement/ContentDisplay.cfm&ContentID=9718