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FDA Regulatory Definitions

February 12, 2016

You heard that a drug in clinical trials was Fast Tracked. Or you heard that a treatment was granted Breakthrough Therapy by the FDA. Or that it got an Orphan Drug status. But what do these regulatory names mean?

Fast Track

In 1997, the FDA created a mechanism whereby important new drugs could get to patients more quickly than the standard and priority review programs already in place. Under it, drugs can be designated as Fast Track if they met two criteria: (1) the drug must show promise in treating a serious life-threatening condition; and (2) the drug must have the potential to address an unmet medical need, meaning that no other drug or remedy either exists or works as well.

Fast Track applications may be evaluated through a “rolling,” or continual, review procedure that allows sponsors to submit to the FDA parts of the application as they are completed, rather than waiting until every section is finished. The FDA receives approximately 100-130 applications a year, and close to 80% will be approved.

Ipilimumab (Yervoy®), a treatment for metastatic melanoma, was approved through Fast Track in March 2011.

Breakthrough Therapy

Breakthrough Therapy may be granted to a drug intended to treat a serious or life-threatening disease, and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies. A drug that receives Breakthrough Therapy designation is eligible for all Fast Track designation features and an FDA commitment to work closely with the sponsor to ensure an efficient drug development program.

The FDA has granted Breakthrough Therapy status since 2012. Approximately 110 requests have been granted by them; 50 were for cancer, and 24 are immunotherapies (48%) for 15 cancer types—acute lymphoblastic leukemia (ALL), bladder cancer, brain cancer, triple-negative breast cancer, colorectal cancer, kidney cancer, chronic lymphocytic leukemia (CLL), Hodgkin and non-Hodgkin lymphoma, non-small cell lung cancer, melanoma, multiple myeloma, Merkel cell cancer, pancreatic cancer, and sarcoma.

Accelerated Approval

The FDA’s Accelerated Approval program began in 1992 to allow faster approval of drugs for serious conditions that fill an unmet medical need. It can take many years to learn whether a drug improves or extends the lives of patients. To speed the evaluation process, the FDA will grant accelerated approval based on whether or not a drug affects a surrogate endpoint. Surrogate endpoints are scientifically validated measures likely to predict the treatment will have the intended clinical benefit (e.g., extending survival) and may include physical signs such as tumor shrinkage. They typically require less time, and, in the case of a cancer patient, it is much faster to measure a reduction in tumor size, for example, than overall patient survival.

Pembrolizumab (Keytruda®) and nivolumab (Opdivo®) for melanoma were approved under this pathway in September and December, respectively, in 2014.

Priority Review

Drugs that have the potential to significantly improve safety or effectiveness may be granted Priority Review after all clinical trials are completed. This allows the drug to be assessed within 6 months, as opposed to the standard 10 months.

Pembrolizumab (Keytruda®) and nivolumab (Opdivo®) were granted Priority Review for their indications. For pembrolizumab, we waited 4 months for it to be approved for melanoma and lung cancer. For nivolumab, we only had to wait 2 months for it to be approved for melanoma, and one week for its expanded prescription for non-small cell lung cancer and kidney cancer.

Approach What It Does
Fast Track Option for “rolling” review process that allows sponsors to submit parts of the application as they are completed, rather than waiting until every section is finished
Breakthrough Therapy Application data submitted as they are accumulated, shortened development and review time
Accelerated Approval Conditional approval granted using a surrogate endpoint
Priority Review Review time is shortened to 6 months (as opposed to the standard 10 months)

According to FDA’s Novel New Drugs Summary, 42% of the novel new drugs—a drug that has previously not been approved by the FDA—approved in 2015 were designated as Fast Track, Breakthrough Therapy, or both. Drugs granted Priority Review made up 53% of the novel new drugs, while 13% were approved using Accelerated Approval. Overall, 60% were designated in one or more categories of Fast Track, Breakthrough Therapy, Priority Review, and/or Accelerated Approval.

For more information on the four above, go to the FDA’s website.

Orphan Drug

In 1983, recognizing that adequate drugs for rare disorders had not been developed in the U.S., Congress passed the Orphan Drug Act to provide incentives to induce companies to develop drugs for individuals with rare and neglected diseases. Orphan Drug status may be granted to drugs and biologics that are intended for the diagnosis, prevention, or treatment of rare diseases or disorders that affect fewer than 200,000 people in the U.S. Orphan Drugs are given Priority Review, allowing them to be assessed within 6 months for approval.

Oncology drugs are almost always given Orphan Drug status if they apply to the FDA, because they are linked to the specific organ (lung, breast, prostate, etc.) where the cancer originates, rather than “cancer” as a whole, single category. More than 3,600 drugs have been given Orphan Drug status.

For more information on Orphan Drug program, visit the FDA’s website.

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