Tracking the Pipeline of Antibiotics in Development
Note: This brief was updated in May 2017 with new data.
Drug-resistant bacteria, or superbugs, present a serious and worsening threat to human health. According to a report from the Centers for Disease Control and Prevention, 2 million Americans acquire serious infections caused by antibiotic-resistant bacteria each year, and 23,000 of them die as a result. Doctors routinely encounter patients with infections that do not respond to available treatment, and when new drugs come to market, bacteria can 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 bring this medicine to the patients who need it most.
Developing new drugs involves a great deal of time, effort, scientific research, and expense. Historical data show that, generally, only 1 out of 5 drugs that reach the initial phase of testing in humans will receive approval from the Food and Drug Administration. Developing antibiotics to treat highly resistant bacterial infections is especially challenging, because only a small number of patients contract these infections and meet the requirements to participate in traditional clinical trials.
To shed light on the antibiotic pipeline, evaluate public policies, and monitor the potential impact on public health, The Pew Charitable Trusts has assessed antibiotics currently in clinical development. The list, which is updated regularly, identifies each drug, manufacturer, potential targets, and stage in the development process. (See the methodology for the criteria used to select the drugs.)
The current assessment of the pipeline shows 41 new antibiotics in development. These drugs would potentially address many, but not all, resistant bacteria. However, given the inevitability that some of these antibiotics will fail to win approval, it is clear that there are too few drugs in development to meet current and anticipated patient needs. As of March 2017:
- Of the 41 antibiotics in development, 15 were in phase 1 clinical trials, 13 in phase 2, and 11 in phase 3, and two drugs had completed phase 3 and their New Drug Applications were under consideration by FDA. Historically, about 60 percent of drugs that enter phase 3 will be approved. (See the glossary of terms for descriptions of each phase.)
- At least 12 of the antibiotics in development have the potential to treat infections caused by Gram-negative ESKAPE pathogens—a critical area of unmet need. Infections caused by these pathogens are not only difficult to treat, but finding new therapies to overcome Gram-negative resistance is also particularly challenging. Additionally, at least 16 of the antibiotics, if approved, could address infections caused by pathogens considered an urgent threat to public health by the CDC. These include drug-resistant gonorrhea, Clostridium difficile infections, and carbapenem-resistant Enterobacteriaceae.
- Fewer than 1 in 3 drugs in the pipeline represents a novel drug class or mechanism of action. Of those, only two are potentially active against Gram-negative ESKAPE pathogens, and one-third of the novel products are in development for C. difficile.
- Of the 36 or so companies with antibiotics in clinical development, only five rank among the top 50 pharmaceutical companies by sales. An additional large company, Novartis, has no drug in clinical testing but employs an active antibiotic research and development team. Over 80 percent of the products in development today are being studied by small companies rather than the large pharmaceutical firms that once dominated this field. Additionally, roughly half of the companies are considered pre-revenue, meaning that they have no products on the market.
Pew and other organizations studying the issue of antibiotic resistance advocate for policies that address scientific, regulatory and economic challenges 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 Generating Antibiotic Incentives Now (GAIN) Act to stimulate the development of new antibiotics. The law increased the commercial value of antibiotics intended for serious or life-threatening infections by extending the period during which the drugs can be sold without competition from generic drugs by five years. Drugs that benefit from GAIN are now in the antibiotic pipeline.
A recent development is the limited-population antibacterial drug pathway (LPAD) authorized in the 21st Century Cures Act, which will provide a unique mechanism for FDA to review and approve new antibiotics specifically for use in patients with unmet medical needs. This process will make the development of the most needed antibiotics more feasible while maintaining FDA’s standards for safety and effectiveness.
A strong pipeline also requires focused efforts to boost basic scientific research and encourage cooperation between academia and industry. Pew is working with key stakeholders to identify ways to effectively address top scientific priorities for the discovery of new antibiotics.
An initial list of antibiotics in clinical development was provided by Citeline Inc.’s Pharmaprojects 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, Helicobacter pylori, and biothreat pathogens.
Also included in the pipeline are treatments for C. difficile infections, many of which act locally in the intestines. C. difficile is often the consequence of systemic antibiotic use, and, while these bacteria are not yet widely resistant to antibiotics, the CDC considers this pathogen an urgent threat. Thousands of Americans contract the illness each year, and an estimated 15,000 die as a result.
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. Pew also works with an external expert, who advises on certain determinations, such as the potential impact of drug candidates on resistant Gram-negative pathogens. This pipeline focuses on antibiotics under development for the U.S. market.This pipeline will be updated biannually, beginning with the March 2015 update. To submit additions, updates, or comments, please contact firstname.lastname@example.org.
In the U.S., there are not enough antibiotics in development to meet current and anticipated patient needs.