Tracking the Pipeline of Antibiotics in Development
Drug-resistant bacteria, or superbugs, present a serious and worsening threat to human health. According to a Centers for Disease Control and Prevention report, 2 million Americans acquire serious infections caused by antibiotic-resistant bacteria each year, and 23,000 of them die.1 Doctors routinely encounter patients with infections that do not respond to available treatment, and when new drugs come to market, bacteria quickly develop resistance. To ensure that the supply of new antibiotics keeps pace with these evolving pathogens, it is necessary to have a robust pipeline of new drugs and innovative pathways to get this medicine to the patients who need it the most.
Developing new drugs involves a great deal of time, effort, scientific research and expense. At best, only 1 out of 5 drugs that make it to the initial phase of testing in humans will receive Food and Drug Administration approval for use.2 Development of antibiotics to treat highly resistant bacterial infections is especially challenging because only a small number of patients contract such infections and meet the requirements to participate in traditional trials.
To shed light on the antibiotic pipeline, evaluate public policies, and monitor the potential impact on public health, Pew has assessed antibiotics currently in clinical development. The list, which will be updated regularly, identifies each drug, its manufacturer, its potential targets, and where it is in the development process. (See Methodology for the criteria used to select the drugs.)
The current assessment of the pipeline shows 38 new antibiotics in development. These drugs would potentially address many, but not all, resistant bacteria. However, given the inevitability that some in development will fail and not be approved, it is clear that there are too few drugs in development to meet current and anticipated patient needs. As of September 2014:
Of the 38 antibiotics in development, 11 were in Phase 1 clinical trials, 18 in Phase 2, seven in Phase 3, and two have submitted new drug applications. Historically, about 60 percent of drugs that enter Phase 3 will be approved.2 (See the glossary of terms for descriptions of each phase.)
Three of the seven antibiotics in Phase 3, as well as two drugs submitted for review by the Food and Drug Administration, had the potential to address the single most pressing unmet need—infections caused by Gram-negative bacilli. The cell structure of Gram-negative bacteria as well as other factors render the pathogens particularly resistant to antibiotics and sometimes multiple ones. The drugs targeting Gram-negative pathogens are being studied for the treatment of life-threatening bloodstream infections, intra-abdominal infections, complicated urinary tract infections, hospital-acquired bacterial pneumonia, and other infections.3
At least 23 of the antibiotics under development were designated as "qualified infectious disease products," meaning they were being studied for serious or life-threatening infections and receiving benefits provided under the Generating Antibiotic Incentives Now, or GAIN, Act of 2012. If approved, these drugs will get extra FDA exclusivity—or time free from generic competition—under GAIN.
At least two antibiotics in early development attack bacteria in an entirely new way by sidestepping the resistance of some bacteria to available antibiotics. Other drugs in the pipeline attack the same targets in bacteria as available drugs but seek to thwart existing resistance by using new chemical compounds.
Of the 29 or so companies developing antibiotics today, only four are in the top 50 pharmaceutical companies by sales. About 80 percent of the products currently in development are being studied by small companies rather than the large pharmaceutical firms that once dominated this field.4 Additionally, about half of the companies are considered pre-revenue, meaning that they have no products currently on the market.
The Pew Charitable Trusts and other organizations studying the issue of antibiotic resistance advocate for polices that address economic and regulatory hurdles to the development of new antibiotics. These efforts aim to keep the pipeline primed with a variety of potential treatments that have the best chance of making it to patients.
Pew supported approval of the GAIN Act to stimulate development of new antibiotics. The law increased the commercial value of antibiotics intended for serious or life-threatening infections by extending by five years the period during which the drugs can be sold without generic competition. Drugs that benefit from GAIN are now in the antibiotic pipeline.
Additional legislative efforts to streamline the regulatory pathway for antibiotics that address unmet medical needs are underway. The Antibiotic Development to Advance Patient Treatment Act has been introduced in Congress. The legislation would help lower the time and costs for developers of antibiotics that address an unmet need.
An initial list of antibiotics in clinical development was provided by Citeline Inc.'s Pharmaproject pipeline drug intelligence service.
The pipeline includes antibiotics intended to treat serious infections that act systemically, or throughout the body, but excludes locally acting drugs such as topical, ophthalmic, and inhaled products. It also does not include biological products, vaccines, new indications or different formulations for previously approved drugs, and drugs used to treat mycobacterial infections such as tuberculosis, Mycobacterium avium complex, H. pylori, and biothreat pathogens.
Also included in the pipeline are treatments for Clostridium difficile infections; although many of these products act locally (in the intestines), the CDC considers this pathogen an urgent threat. While C. difficile infections are generally not resistant to the antibiotics used to treat them, there is a clear need for new products because they affect thousands of Americans each year and most of the infections result from antibiotic use.
Pew supplemented the data provided by Citeline with other public information—specifically, trials registered in www.clinicaltrials.gov, articles published in scientific literature or trade press, and company communications. This pipeline focuses on antibiotics under development for the U.S. market.
This pipeline will be updated quarterly. To submit additions, updates, or comments, please contact Rachel Zetts at firstname.lastname@example.org.
- Centers for Disease Control and Prevention, Antibiotic Resistance Threats to the United States, 2013, http://www.cdc.gov/drugresistance/threat-report-2013/index.html.
- Michael Hay et al., “Clinical Development Success Rates for Investigational Drugs,” Nature Biotechnology 32, (2014): 40–51.
- H.W. Boucher et al., "10 x '20 Progress-Development of New Drugs Against Gram-Negative Bacilli: An Update From the Infectious Diseases Society of America," Clinical Infectious Diseases 56 (2013): 1685-94. Carbavance included in count based on entry into Phase 3 trial specific to carbapenem-resistant Enterobacteriaceae.
- Waseem Noor, "Pharm Exec's Pharma 50 2014," PharmExec, June 9, 2014, http://www.pharmexec.com/pharmexec/Noteworthy/Pharm-Execs-Pharma-50-2014/ArticleStandard/Article/detail/845310.