CDER Approved Many Innovative Drugs in 2014

By: John Jenkins, M.D.

Each year, FDA’s Center for Drug Evaluation and Research (CDER) will typically approve more than 100 new medications. A portion of those are novel new drugs, medications that have not previously been approved by FDA and are often among the most innovative products serving previously unmet medical needs or otherwise significantly helping to advance patient care and public health.

John JenkinsThis year, the news media has been concentrating on the number of novel new drugs – either new molecular entities or new therapeutic biologics – approved by CDER in 2014. And that’s understandable because we approved 41 novel drugs this year, the most in nearly 20 years. But instead of looking at the approval tally, we prefer to focus on the significant benefits that many of these drugs bring to patients and the steps that CDER took to get these products to market in a timely manner while maintaining FDA’s standards for safety, effectiveness, and quality.

Many of the 41 new drugs have the potential to add significant clinical value to the care of thousands of patients with serious or life-threatening diseases. They include eight new drugs for treating patients with various types of cancer, four new drugs to treat type-2 diabetes, four new antibiotics to treat serious infections, and two new products to treat patients with hepatitis C.

Moreover, consider these facts:

  • Seventeen (41%) of the 41 novel new drugs were approved to treat rare diseases that affect 200,000 or fewer Americans. This is the highest yearly total of such drugs ever — surpassing the previous high of 13 from 2012. These approvals are particularly significant because patients with rare diseases often have few or no drugs available to treat their conditions.
  • Seventeen (41%) of the 41 novel new drugs are identified by CDER as “First-in-Class,” one indicator of a drug’s degree of innovation. The total for First-In-Class approvals in 2014 approaches the highest yearly total of 20 reported in 2012.

To expedite the development and review of these products, CDER used a number of regulatory programs, including Fast Track, Breakthrough Therapy, Priority Review, and Accelerated Approval.

  • Fast Track and Breakthrough Therapy designations are designed to speed the development of promising new drugs intended to treat serious conditions with unmet medical needs. Almost half – 19 or 46% of the 41 novel new drugs approved in 2014 — were designated as Fast Track, Breakthrough, or both.
  • Twenty-five (61%) of the 41 novel new drugs were designated for Priority Review. These are drugs in which CDER sees potential for providing a significant advance in medical care, and sets their review target to within six instead of the standard 10 months.
  • Six (20%) of the 41 novel new drugs were approved under FDA’s Accelerated Approval program, which allows early approval of a drug for a serious or life-threatening illness that offers a benefit over current treatments. Accelerated Approval is based on a “surrogate endpoint” or an intermediate clinical endpoint that is thought to be “reasonably likely to predict clinical benefit.” Additional clinical trials are required after approval to confirm the predicted clinical benefit. A surrogate endpoint is a marker of drug effect (e.g., an effect on a lab value or tumor size) that does not directly represent an improvement in how a patient feels or functions, but is expected to predict such a benefit.

Here are a few other ways we assess our contributions to last year’s approvals:

  • Under the Prescription Drug User Fee Act (PDUFA), sponsors pay fees when they submit a product application. This money is used to provide FDA with additional resources to meet performance goals, such as a goal date for completing its review of the application. In 2014, CDER acted on or before the PDUFA goal date for 40 (98%) of the 41 novel new drugs approved.
  • CDER approved more than three-quarters — 32 (78%) — of the 41 novel new drugs on the “first cycle” of review, meaning without requests for additional information that would delay approval and lead to another cycle of review.
  • Nearly two-thirds of the novel new drugs – 26 (63%) — were approved in the U.S. before approval in another country.

It’s been another strong year for approval of novel new drugs for patients in need. We are proud of our role in helping to safely and efficiently bring important new medications to the American public.

Our Novel New Drug Summary for 2014 provides more details. A current list of CDER’s 2014 novel new drug approvals is available on our Web site.

John Jenkins, M.D., is Director of the Office of New Drugs 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

Early communication: A key to reduced drug development and approval times

By: Anne Pariser, M.D.

From “test tube” to market typically takes a new drug more than 10 years.  FDA has been working hard at many points along a drug’s developmental path to reduce this time and bring safe and effective new therapies to Americans as efficiently as possible. 

Much has been said about FDA’s success in using its “expedited approval” tools, specifically Priority Review and Accelerated Approval, to support innovative new drugs. These are important tools that FDA can use once a marketing application is submitted. For instance, last year, FDA’s Center for Drug Evaluation and Research (CDER) approved 39 novel medications, almost half of which benefited from one (or both) of these expedited approval tools. According to a recent FDA report, this is a 63% increase over the average number of annual approvals since 2002. 

But less has been said about FDA’s “expedited development” tools, which help foster new drug innovation during the investigational phases of drug research and development, well before a marketing application for a new drug is even submitted to FDA. Among these tools are more frequent and earlier opportunities for communication between FDA and drug developers. FDA’s Fast Track designation for drugs with the potential to address unmet medical needs is an example. For many years, Fast Track has helped speed new drug development by encouraging more communication early in the development process. In 2012, about 40% of CDER’s novel new drug approvals were drugs that were given this Fast Track designation.     

Just this past year, the Food and Drug Administration Safety and Innovation Act (FDASIA) authorized FDA to use a new Breakthrough designation for investigational new drugs when preliminary clinical data suggest that the drug may provide a substantial improvement over existing therapies for patients with serious or life-threatening diseases. The concept behind Breakthrough is that, with increased communication, FDA will work with new drug developers to help design efficient ways to study the safety and effectiveness of their drug. This early assistance can help ensure that the results of clinical trials provide the evidence that FDA must have to determine whether or not a drug is safe and effective for approval. A growing number of drug developers are already taking advantage of Breakthrough.

But even before Breakthrough had been authorized by FDASIA, FDA was working to encourage communication opportunities for drug developers to meet with FDA to help make sure their clinical trial designs and development plans offered the best chances of efficient, safe, and timely development and approval. These opportunities are available at the start of a drug’s clinical development cycle: right before the earliest phases of human testing known as the “pre-investigational new drug (IND) phase” (fittingly called pre-IND meetings) and continue throughout drug development.

Early communication in action

Recently, FDA has taken a look at the development times of new drugs that were approved with the benefit of pre-IND meetings and compared them to the development times for drugs that were approved without such meetings. The findings underscore the value of early communication. For those new drugs for which a pre-IND meeting between the drug developer and FDA was held, average clinical development times were substantially shorter than when a meeting was not held. For instance, for all new drugs approved between 2010 and 2012, the average clinical development time was more than 3 years faster when a pre-IND meeting was held than it was for drugs approved without a pre-IND meeting.

For orphan drugs used to treat rare diseases, the development time for products with a pre-IND meeting was 6 years shorter on average or about half of what it was for those orphan drugs that did not have such a meeting. Early communication is especially important for orphan drugs because these products require special attention and thus early talks can be especially beneficial.

Many factors can influence the speed and efficiency of a drug development program. Nevertheless, FDA strongly believes in the value of effective communication during the drug development and approval process, especially for novel development programs when established regulatory pathways do not exist. FDA is committed to working with drug developers to ensure efficient and effective drug development programs whenever possible.

Thirty-nine novel new drug approvals last year is encouraging – one third of which are indicated to treat rare diseases – and many of these new drugs are now making valuable contributions to public health inAmerica. FDA will continue to do its part to help bring safe and effective new drugs to market as soon as possible. We will continue efforts to enhance communication as a critical part of the drug research, development, and regulatory process – especially since it is so clear that communications can make a big difference.

Anne Pariser, M.D., is Associate Director for Rare Diseases, Office of New Drugs, Rare Diseases Program at FDA’s Center for Drug Evaluation and Research