Three encouraging steps towards new antibiotics

By: Janet Woodcock, M.D.

You may have been hearing about a variety of Federal Government actions to address the growing need for new antibiotics. For instance, in an FDA Voice blog last week Commissioner Hamburg discussed the President’s national strategy for Combating Antibiotic Resistant Bacteria (CARB) and our collaboration with a wide variety of organizations to address this issue. You may have also noticed another recent blog talking about FDA’s work on the Generating Antibiotics Incentives Now Act (GAIN Act), the Antibacterial Drug Development Task Force, a public meeting, a Federal Register Notice, and multiple guidance documents, all aimed at building up the nation’s arsenal of effective antimicrobial drugs.

Janet WoodcockThere are many government activities in this area, so I’d like to boil things down a bit. A critical fact is that our efforts are starting to show signs of success. Over the last few months, FDA has approved three new antibiotics to treat patients with acute bacterial skin and skin structure infections (ABSSSI) caused by bacteria like Staphylococcus aureus, including methicillin-resistant strains, also known as MRSA infections.

  • On May 23, FDA approved Dalvance (dalbavancin), an injectable drug, administered intravenously in two doses one week apart.
  • On June 20, FDA approved Sivextro (tedizolid phosphate), available for intravenous and oral use, administered once daily for six days.
  • On August 6, FDA approved Orbactiv (oritavancin), an injectable drug administered as a single dose to comprise a full course of therapy.

In these approvals, the drug’s manufacturer was able to take advantage of recently enacted incentives to help bring new antimicrobials to market. Each of these drugs was approved after being designated as a Qualified Infectious Disease Product (QIDP) under the GAIN Act. As part of this QIDP designation, FDA’s review of the drug application was expedited. The designation also qualified the drugs for five years of marketing exclusivity to be added to certain exclusivity already provided by the Food, Drug, and Cosmetic Act. To date, FDA has granted the QIDP designation to 39 antibiotics under development.

Development of these three new antibiotics was also helped a great deal by the scientific collaboration among stakeholders dedicated to advancing new antimicrobial therapies. The Biomarkers Consortium of the Foundation for the National Institutes of Health, academic and industry experts, and other contributors made valuable recommendations to the FDA regarding designing scientifically sound studies to show the effectiveness of these drugs in clinical trials.

We still have a long way to go in getting a leg up on building a new and more effective arsenal of antimicrobial products. And once approved, it will be critical for health care professionals to appropriately prescribe these new antibiotics. But with ongoing collaborative, concerted efforts by the many public and private stakeholders, we can continue to advance and help build a national antibacterial research and development enterprise capable of bringing new drugs to the patients who need them. These three approvals are an encouraging start!

Janet Woodcock, M.D., is the Director of FDA’s Center for Drug Evaluation and Research

Learn more by reading Dr. Woodcock’s testimony: 21st Century Cures: Examining Ways to Combat Antibiotic Resistance and Foster New Drug Development.:

FDA’s multi-pronged approach helps meet the challenge of bringing new and innovative antibiotics to patients who need them

By: Edward M. Cox, MD, MPH

With a growing number of infections becoming increasingly resistant to our current arsenal of antibiotics, developing new antibiotics to treat serious or life-threatening infections has become a key priority.

Edward Cox interview

There are significant scientific and economic challenges inherent to the development of new antibiotics. From a scientific standpoint, many patients with bacterial infections are often very sick and need to begin antibiotic therapy immediately, without further complications that enrollment in a clinical trial might involve. Moreover, it can be difficult to conduct a clinical trial involving very sick patients.

From an economic standpoint, antibiotics may be perceived as less potentially profitable for a company because they are generally taken only for a short period of time and often only for one course of treatment, by any given patient. Compare this to the long, dependable income stream from a diabetes medicine or a blood pressure medicine that a patient takes indefinitely, often for the rest of their life. These economic realities, which are rooted in the biology of acute bacterial infections, can make it challenging for a company to justify large expenditures for the development of drugs in this area, as a recent report by Eastern Research Group (ERG) affirms.

Provisions in a law passed a little over two years ago, commonly known as the GAIN Act, or the Generating Antibiotics Incentives Now Act, is helping to stimulate the development of new antibiotics. Under GAIN, certain antibacterial or antifungal drugs intended to treat serious or life-threatening infections can be designated “Qualified Infectious Disease Products” (QIDPs). As part of its QIDP designation, a drug receives priority review and can also receive fast track designation at the sponsor’s request. At the time of approval, a product with QIDP designation may be eligible for an additional five years of marketing exclusivity, exclusive marketing rights without competing with a generic drug product. To date FDA has granted 52 QIDP designations to 35 different unique molecules. We are already beginning to approve new antibacterial drugs with this beneficial QIDP designation.

FDA is working hard to streamline requirements for clinical trials for studying new antibacterial drugs and the provisions of the GAIN act are being actively implemented, but more is needed. There are still significant economic and scientific challenges in the development of new antibacterial drugs that need to be addressed. Additional financial incentives as well as new approaches for studying antibacterial drugs such as common clinical trial protocols could provide other important means to stimulate antibacterial drug development. We also need cutting-edge science to stimulate the development of new and innovative antibacterial drugs. To help drive this effort, FDA has assembled our Antibacterial Drug Development Task Force, a group of expert scientists and clinicians from within FDA, to consider opportunities to promote antibacterial drug development.

To advance this field, our Task Force is working with many leaders including those drawn from academia, regulated industry, professional societies, patient advocacy groups and government agencies. For example, FDA has contributed to the efforts of the Biomarkers Consortium of the Foundation for the National Institutes of Health to develop new endpoints for studying antibacterial drugs. FDA also works closely with the Clinical Trials Transformation Initiative (CTTI), a key group of dedicated scientists focused on advancing clinical trials for more efficient drug development. As a result, FDA and CTTI have helped convene a variety of important scientific meetings and activities on vital topics related to efficient clinical trial designs for testing new antibiotics. Our Task Force has also helped FDA team up with colleagues at the Brookings Institution’s Engelberg Center for Health Care Reform to help galvanize the scientific community’s efforts in new antibiotic drug development. August, 2012 began the first Brookings Council for Antibacterial Drug Development (BCADD) meeting, with meetings that occur approximately twice a year.

FDA and our Task Force members have also been busy on our own.  In February of 2013 we held a public meeting focused on creating an alternative approval pathway for certain drugs, such as antibacterial drugs, that are intended to address unmet medical need. We have also asked the public for their thoughts; in March of 2013, we issued a Federal Register Notice seeking input from the public on a wide range of topics related to antibacterial drug development. FDA has generated a number of guidance documents for industry, in draft and final form, that describe FDA’s scientific thinking with regard to developing new antibacterial drugs.

As part of our Task Force’s collaborative efforts, FDA is working closely with The National Institutes of Health (NIH) to further advance the development of new antibacterial drugs. Together, we are hosting a two-day Public Workshop to identify strategies for promoting clinical trials for antibacterial drugs and encouraging partnerships to accelerate their development. The ERG report will be presented at the workshop and other specific issues will be discussed including:

  • Priorities and strategic approaches to conducting clinical trials for antibacterial drugs
  • Regulatory pathways—including streamlined development programs for antibacterial drugs for patients with limited or no treatment options
  • Clinical trial design issues such as the development of common clinical protocols; using common control groups; statistical analysis issues; sharing data across trials (and data standards); appropriate clinical trial endpoints; and lessons learned from other therapeutic areas
  • The role of public-private partnerships in advancing the scientific and clinical trials enterprises

The work of the FDA Task Force as well as the GAIN Act have provided good first steps toward strengthening the antibacterial drug pipeline, but as the findings from the ERG report indicate, the forecast for antibacterial drug development likely will include a less than robust pipeline. Thus, additional attention on both financial incentives, new approaches for studying antibacterial drugs such as common protocols, as well as streamlined development pathways, likely will be needed to improve the climate.

Edward M. Cox, MD, MPH, is Director, Office of Antimicrobial Products, in FDA’s Center for Drug Evaluation and Research