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

“Breakthrough” Designation … Another Powerful Tool in FDA’s Toolbox for Expediting the Development and Review of Promising New Drugs for Serious Conditions

By: Janet Woodcock, M.D.

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

In fiscal year 2012, FDA approved 35 novel new drugs, also known as “new molecular entities.” Among these new products were drugs to treat patients with unmet medical needs, such as a groundbreaking treatment for a form of cystic fibrosis, the first FDA-approved human cord blood product for hematopoietic reconstitution, used to help patients with blood forming disorders, and the first drug to treat advanced basal cell carcinoma (a form of the most common skin cancer).

To enable our ongoing efforts to bring innovative drug products to the public as efficiently as possible, FDA relies heavily on several expedited development and review tools such as fast track designation, the accelerated approval pathway and priority review designation. For instance, 56 percent of the novel drugs approved by the Center for Drug Evaluation and Research in calendar year 2012 used some combination of these tools to speed promising therapies to patients with serious conditions. And any given drug may have received multiple expedited program designations. (See a brief summary of how each of these tools helps FDA shorten the development and review of promising new therapies.)

In July 2012, a provision in the new law called the Food and Drug Administration Safety and Innovation Act, or FDASIA for short, gave FDA another powerful expedited development tool, known as the “breakthrough therapy” designation. This new designation is now helping FDA assist drug developers expedite the development of new drugs with preliminary clinical evidence that indicates the drug may offer a substantial improvement over available therapies for patients with serious or life-threatening diseases. Although the designation is not yet even a year old, FDA has received 62 requests to grant this new designation to products under development. We have been very active on this subject, meeting with companies and discussing ways to expedite the drug development process for drugs that show striking early results. We have already granted the breakthrough designation to 20 potential innovative new drugs that have shown encouraging early clinical results.

Drug developers should have a clear understanding of all of FDA’s expedited development and review tools. To help industry better understand each tool, including when the tools can be used and the features of each, we have just published an industry draft guidance titled Expedited Programs for Serious Conditions — Drugs and BiologicsAmong other important information, the draft guidance describes FDA’s policies and the threshold criteria for each expedited program, defines and discusses important concepts, including serious condition, unmet medical need, and available therapy, and provides some general considerations for products utilizing an expedited program, such as manufacturing and product quality, nonclinical considerations, and clinical inspection considerations.

The breakthrough therapy designation gives us another tool in our “toolbox” to help expedite the development and review of new drugs to treat patients with serious medical conditions and little or no treatment options. We’ll continue to use the new breakthrough therapy designation and our existing tools to help make our expedited programs even more effective.

We’ve said it before — and I believe it’s worth repeating — our decision-making on whether to approve a drug always involves an evaluation of many factors, such as the seriousness of the disease.  However, ultimately any drug approved must show that its benefits outweigh its risks and regardless of which expedited development or review program or programs are used, FDA does not compromise its safety or efficacy standards in exchange for rapid approval. Like all drugs we approve, those approved after having been designated as breakthrough therapies will meet our usual rigorous standards for safety and effectiveness.

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

Setting the Bar High for FDA

By: Margaret A. Hamburg, M.D.

Rick Pazdur receiving ASCO Public Service Award

Rick Pazdur, accompanied by Margaret Hamburg, receiving ASCO Public Service Award

To say that Rick Pazdur faces enormous challenges in his job is an understatement. To say that he faces each day with energy, insight and resolve still falls short of the mark.

It’s my privilege to tell you that the American Society of Clinical Oncology (ASCO) has awarded Dr. Pazdur with its prestigious Public Service Award for his dedication to improving the lives of people living with cancer.

As director of the Office of Hematology and Oncology Products (OHOP) at FDA, Dr. Pazdur leads a staff of more than 130 oncologists, toxicologists and other specialists.

Their mission is making safe and effective drugs for cancer and hematologic (blood-related) conditions available to the patients who need them. The office is committed to facilitating rapid development, review and action on promising new treatments for these diseases.

Dr. Pazdur sets the bar high. His demand for excellence in his staff as well as in the treatments they review is unparalleled. Ultimately, Dr .Pazdur and his staff must decide whether or not an investigational drug can be tested in a clinical trial and, after testing, be approved for more widespread use. Sometimes, after careful investigation, they conclude that a drug has not been proven effective enough to outweigh the potential risks. These are the types of challenges and the tough decisions that Dr. Pazdur faces on a daily basis. A man of personal integrity with great compassion for those who are ill, he nonetheless is  often the recipient of criticism from patients, advocacy groups, drug companies and others. I have heard him say ruefully, but with characteristic humor, that you can’t win in this job—that if he approves a drug, he’s accused of lowering standards.  And if he doesn’t, he is insensitive to the plight of patients with cancer. Nothing could be farther from the truth.

Since his arrival at FDA in 1999, Dr. Pazdur has worked tirelessly to speed the development and availability of drugs that treat serious diseases, especially when the drugs are the first available treatment or have advantages over existing therapies. He has made a special effort to reach out to patient and advocacy groups, professional associations and foreign regulatory agencies. In 2012, nearly 40 percent of the new molecular entities approved in the Center for Drug Evaluation and Research were to treat cancer, often when few therapeutic options previously existed.

Members of Dr. Pazdur’s staff speak with warmth and enthusiasm of his dedication to cancer patients and his unflagging efforts to streamline the drug approval process. They call him not just a manager, but “a visionary,” and “one of the most unique people I know.” I quite agree.

To one of the most dedicated and accomplished people I know: It’s a pleasure to work at your side, Dr. Pazdur. Congratulations for this well-deserved honor.

Margaret A. Hamburg, M.D. is Commissioner of the Food and Drug Administration