“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

Skin Deep: New Skin Cancer Therapies Offer Progress for Patients

By: Patricia Keegan, M.D.

Skin cancer is the most common form of cancer in the United States and rates of new cases continue to increase, especially in younger populations. Some of that increase may be attributed to greater public awareness about the risks of skin cancer, resulting in more patients inspecting their skin and talking with their doctors about an appropriate diagnosis. 

There are three main types of skin cancer: basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma. Melanoma is much less common than basal cell and squamous cell skin cancers but it is far more dangerous – it’s the leading cause of death from skin disease and is emerging as one of the most frequently diagnosed forms of cancer. In 2011, there were an estimated 70,230 new cases and 8,790 deaths from melanoma in the United States.  

But last year represented a tremendous leap forward for patients living with late-stage (metastatic) melanoma. For the first time in FDA’s history, we approved two novel therapies that extended the lives of patients (overall survival) with late-stage melanoma. Cancers that spread are frequently more difficult to treat and associated with poor outcomes for patients.

The two treatments, Yervoy (ipilimumab) and Zelboraf (vemurafenib), are not only unique because of their ability to extend a person’s life, but also recognized for the role they play in attacking the cancer itself.

Yervoy blocks a molecule known as cytotoxic T-lymphocyte antigen or CTLA-4 and works with a person’s immune system to recognize, target, and attack cells in melanoma tumors.

In 2011, the FDA approved Zelboraf, a personalized medicine to treat patients with melanoma whose tumors have the BRAF V600E gene mutation. With the aid of an FDA-approved test, patients can be selected to receive treatment with the drug, which blocks the ability of mutated BRAF to make tumors grow.

Today’s approval of Erivedge (vismodegib) for patients with late-stage or advanced basal cell carcinoma is the latest treatment advance for patients with the most common type of skin cancer, which is usually cured by surgery to remove the cancer. The treatment is the first drug approved for the small fraction of patients whose tumors are not controlled by or who cannot receive curative local therapy.

These important and innovative new therapies are encouraging for the millions of patients currently living with a form of late-stage skin cancer. Their availability today for patients is a testament to the ingenuity and dedication of the academic researchers and companies who studied and developed them; the patients willing participate in the investigational trials; and the FDA staff dedicated to timely scientific reviews with an eye to what is best for patients.

Patricia Keegan, M.D., is Director for the Division of Oncology Products 2 in the Office of Hematology and Oncology Products in FDA’s Center for Drug Evaluation and Research