In calendar year 2015, FDA’s Center for Drug Evaluation and Research (CDER) approved 45 novel new drugs, approved as new molecular entities (NMEs) under New Drug Applications (NDAs) or as new therapeutic biologics under Biologics License Applications (BLAs).
Novel new drugs are often innovative products that serve previously unmet medical needs or otherwise significantly help to advance patient care and public health. NMEs have chemical structures that have never been approved before. However, in some cases an NME may have actions similar to earlier drugs and may not necessarily offer unique clinical advantages over existing therapies. This report summarizes all of the 2015 NME and novel new BLA approvals, emphasizing those that offer new and innovative treatments to patients in need.
Applications for new approvals remain steady
CDER approved a higher than average number of novel new drugs in 2015; however, the number of applications for these drugs that sponsors have submitted over time has remained relatively stable.
The points connected by lines in the graph below indicate the number of new NDA and BLA applications for new molecular entities and new therapeutic biologics CDER has received and filed for approval during the last 10 years. From 2006 through 2014, CDER filed an average of about 35 applications for novel new drugs per year. CDER estimates 40 filings for 2015, which is consistent with previous years in this decade.
Below lists CDER’s novel new drugs of 2015.* (see New Molecular Entity and Therapeutic Biologics of 2015 for their non-proprietary names, approval dates, and what they are used for.)
Addyi, Alecensa, Aristada, Avycaz, Bridion, Cholbam, Corlanor, Cosentyx, Cotellic, Cresemba, Daklinza, Darzalex, Empliciti, Entresto, Farydak, Genvoya, Ibrance, Kanuma, Kengreal, Kybella, Lenvima, Lonsurf, Natpara, Ninlaro, Nucala, Odomzo, Orkambi, Portrazza, Praluent, Praxbind, Repatha, Rexulti, Savaysa, Strensiq, Tagrisso, Tresiba, Unituxin, Uptravi, Varubi, Veltassa, Viberzi, Vraylar, Xuriden, Yondelis, Zurampic.
* This information is accurate as of December 31, 2015. In rare instances, it may be necessary for FDA to change a drug’s new molecular entity (NME) designation or the status of its application as a novel new biologics license application (BLA). For instance, new information may become available which could lead to a reconsideration of the original designation or status. If changes must be made to a drug’s designation or the status of an application as a novel BLA, the Agency intends to communicate the nature of, and the reason for, any revisions as appropriate.
Table: CDER New Molecular Entity (NME) and New Biologic License Application (BLA) Filings and Approvals
|
Calendar Year
|
NME/BLA Filings
|
NME/BLA Approvals
|
|
2006
|
26
|
22
|
|
2007
|
35
|
18
|
|
2008
|
34
|
24
|
|
2009
|
36
|
26
|
|
2010
|
23
|
21
|
|
2011
|
41
|
30
|
|
2012
|
41
|
39
|
|
2013
|
36
|
27
|
|
2014
|
41
|
41
|
|
2015*
|
40
|
45
|
Impact
Impact on Public Health
Many of the 45 novel new drugs CDER approved in 2015 are notable for their potential positive impact and unique contributions to quality medical care and public health.
First-in-Class
CDER identified 16 of the 45 novel new drugs approved in 2015 (36%) as First-in-Class, one indicator of the innovative nature of a drug. These drugs often have mechanisms of action different from those of existing therapies. This First-in-Class approval rate is one factor that suggests the 2015 group of novel new approvals is a field comprised of many innovative products.
Addyi, Bridion, Corlanor, Cosentyx, Darzalex, Empliciti, Entresto, Ibrance, Kanuma, Nucala, Orkambi, Praluent, Praxbind, Strensiq, Unituxin, Xuriden
Noteworthy First-in-Class products include:
Bridion – To reverse post-surgical neuromuscular blockade caused by certain kinds of anesthesia
Ibrance - To treat advanced (metastatic) breast cancer
Praxbind – To reverse adverse anticoagulant effects caused by the blood-thinner drug, dabigatran
Drugs for Rare Diseases
About 47% of the novel new drugs approved in 2015 (21 of 45) were approved to treat rare or “orphan” diseases that affect 200,000 or fewer Americans. This is significant because patients with rare diseases often have few or no drugs available to treat their conditions.
Alecensa, Cholbam, Cotellic, Cresemba, Darzalex, Empliciti, Farydak, Kanuma, Lenvima, Natpara, Ninlaro, Orkambi, Portrazza, Praxbind, Repatha*, Strensiq, Tagrisso, Unituxin, Uptravi, Xuriden, Yondelis
* Repatha was submitted with two indications. One indication received Orphan designation while the other did not.
Noteworthy examples of drugs to treat rare diseases among the 2015 novel new drugs include:
Kanuma – To treat lysosomal acid lipase deficiency, a rare inherited genetic disorder that does not allow the body to produce an enzyme responsible for breaking down fats, and can lead to liver disease, cardiovascular disease, and life-threatening organ damage.
Orkambi – A therapy for the lung disease, cystic fibrosis.
Strensiq - Long-term enzyme replacement therapy in patients with infantile- and juvenile - onset hypophosphatasia, a serious and sometimes fatal bone disease.
Unituxin - To treat pediatric patients with high-risk neuroblastoma (brain tumors).
Xuriden – To treat patients with hereditary orotic aciduria, a condition that can result in blood abnormalities (anemia, decreased white blood cell count, decreased neutrophil count), urinary tract obstruction, failure to thrive, and developmental delays.
Notable Novel New Drugs of 2015: Another strong year for quality
In addition to the noteworthy examples of innovative First-in-Class and “orphan” new products mentioned previously above, the 2015 novel new drug field also includes a variety of other notable drugs. These include the antibacterial drug Avycaz, to treat complicated intra-abdominal infections and complicated urinary tract infections, and the antifungal product Cresemba, to treat invasive aspergillosis and invasive mucormycosis, rare but serious infections. Also, the heart drugs, Entresto, to treat heart failure, and Corlanor, to reduce hospitalization from worsening heart failure; and the hypercholesterolemia (high cholesterol) treatments,Praluent, to treat certain patients with hard to treat heterozygous familiar hypercholesterolemia and Repatha, to treat this same condition as well as homozygous familial hypercholesterolemia (a rare disease).
Additional noteworthy cancer treatments include Darzalex, Empliciti, Farydak, and Ninlaro, to treat patients with multiple myeloma (a type of bone cancer), Alecensa and Tagrisso, to treat certain patients with non-small cell lung cancer, Cotellic, to treat certain patients with metastatic melanoma (skin cancer), Lonsurf, for the treatment of certain patients with metastatic colorectal cancer, and, Yondelis,for treatment of soft tissue carcinoma (cancer of the inner or outer surfaces of the body).
The year’s notable approvals also include Viberzi, to treat patients who have irritable bowel syndrome with diarrhea (IBS-D), Veltassa, to treat hyperkalemia (elevated potassium in the blood), and Daklinza, to treat chronic hepatitis C virus genotype 3 infections.
INNOVATION
Methods for expediting innovative novel new drugs to market
CDER used a number of regulatory methods to expedite the development and approval of novel new drugs in 2015. These involved the following four expedited pathways: Fast Track, Breakthrough, Priority Review, and Accelerated Approval.
Fast Track
Fourteen of the 2015 novel new drugs (31%) were designated by CDER as Fast Track, meaning drugs with the potential to address unmet medical needs. Fast Track speeds new drug development and review, for instance, by increasing the level of communication FDA allocates to drug developers and by enabling CDER to review portions of a drug application ahead of the submission of the complete application.
Avycaz, Corlanor, Cotellic, Daklinza, Darzalex, Entresto, Genvoya, Kanuma, Lonsurf, Orkambi, Portrazza, Strensiq, Tagrisso, Viberzi
Breakthrough
CDER designated ten of the 2015 novel new drugs (22%) as Breakthrough therapies, meaning drugs with preliminary clinical evidence demonstrating that the drug may result in substantial improvement on at least one clinically significant endpoint (i.e., study result) over other available therapies. A breakthrough therapy designation includes all of the Fast Track program features, as well as more intensive FDA guidance on an efficient drug development program. Breakthrough status is designed to help shorten the development time of a potential new therapy.
Alecensa, Darzalex, Empliciti, Ibrance, Kanuma, Orkambi, Praxbind, Strensiq, Tagrisso, Xuriden
Priority Review
Twenty-four of the 2015 novel new drugs (53%) were designated Priority Review, in which CDER determined that the drug could potentially provide a significant advance in medical care and set a target to review the drug within six months instead of the standard 10 months.*
Alecensa, Avycaz, Bridion, Cholbam, Corlanor, Cotellic, Cresemba, Daklinza, Darzalex, Empliciti, Entresto, Farydak, Ibrance, Kanuma, Lenvima, Ninlaro, Orkambi, Praxbind, Strensiq, Tagrisso, Unituxin, Viberzi, Xuriden, Yondelis
*In some instances, priority review is assigned as a result of the sponsor redeeming a voucher for priority review under CDER’s Priority Review Voucher program, which may mean the drug does not potentially provide a significant advance. Such drugs are not included in the list above.
Accelerated Approval
CDER approved six of the 2015 novel new drugs (13%) 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. This approval is based on a “surrogate endpoint” (e.g., a laboratory measure) or other clinical measure that we consider reasonably likely to predict a clinical benefit of the drug. Once Accelerated Approval is granted, the drug must undergo additional testing to confirm that benefit; this speeds the availability of the drug to patients who need it.
Alecensa, Darzalex, Farydak, Ibrance, Tagrisso, Praxbind
Overall use of expedited development and review methods
Twenty-seven of the 2015 novel new drugs (60%) were designated in one or more expedited categories of Fast Track, Breakthrough, Priority Review, and/or Accelerated Approval. Each of these designations helps expedite the speed of the development and/or approval process and is designed to help bring important medications to the market as quickly as possible.
Alecensa, Avycaz, Bridion, Cholbam, Corlanor, Cotellic, Cresemba, Daklinza, Darzalex, Empliciti, Entresto, Farydak, Genvoya, Ibrance, Kanuma, Lenvima, Lonsurf, Ninlaro, Orkambi, Portrazza, Praxbind, Strensiq, Tagrisso, Unituxin, Viberzi, Xuriden, Yondelis
Qualified Infectious Disease Program Designations
The Generating Antibiotics Incentives Now Act (GAIN Act) provides incentives to help bring new antibiotics and other antimicrobials to market. A drug with particular promise can be designated as a Qualified Infectious Disease Product (QIDP) by authority of the GAIN Act. In 2015, CDER approved two novel new drugs with this designation.
Avycaz, Cresemba
PREDICTABILITY
PDUFA Goals Met
Under the Prescription Drug User Fee Act (PDUFA), sponsors are assessed user fees that provide FDA with the additional resources needed to meet performance goals. Throughout the year, CDER was able to meet or exceed most PDUFA goal dates for application review, agreed to with the pharmaceutical industry and approved by Congress. In 2015, CDER met its PDUFA goal dates for 96% of the novel new drugs approved (43 of 45).
Addyi, Alecensa, Avycaz, Bridion, Corlanor, Cosentyx, Cotellic, Cresemba, Daklinza, Darzalex, Empliciti, Entresto, Farydak, Genvoya, Ibrance, Kanuma, Kengreal, Kybella, Lenvima, Lonsurf, Natpara, Ninlaro, Nucala, Odomzo, Orkambi, Portrazza, Praluent, Praxbind, Repatha, Rexulti, Savaysa, Strensiq, Tagrisso, Tresiba, Unituxin, Uptravi, Varubi, Veltassa, Viberzi, Vraylar, Xuriden, Yondelis, Zurampic
ACCESS
First Cycle Approval
CDER approved most of the novel new drugs of 2015 (39 of 45, 87%) on the “first cycle” of review, meaning without requests for additional information that would delay approval and lead to another cycle of review.
Alecensa, Aristada, Avycaz, Cholbam, Corlanor, Cosentyx, Cotellic, Cresemba, Darzalex, Empliciti, Entresto, Farydak, Genvoya, Ibrance, Kanuma, Kybella, Lenvima, Lonsurf, Natpara, Ninlaro, Nucala, Odomzo, Orkambi, Portrazza, Praluent, Praxbind, Repatha, Rexulti, Savaysa, Strensiq, Tagrisso, Unituxin, Uptravi, Varubi, Veltassa, Viberzi, Xuriden, Yondelis, Zurampic
Approval in the U.S. Before Other Countries
Comparing approval to other countries offers another measure of approval efficiency. Although regulatory processes differ widely between FDA and those of regulatory agencies in other countries, about two-thirds of the novel new drugs approved in 2015 (29 of 45, 64%) were approved in the United States before receiving approval in any other country.
Addyi, Aristada, Avycaz, Cresemba, Darzalex, Empliciti, Entresto, Farydak, Genvoya, Ibrance, Kybella, Lenvima, Natpara, Ninlaro, Nucala, Orkambi, Portrazza, Praluent, Praxbind, Rexulti, Tagrisso, Unituxin, Uptravi, Varubi, Veltassa, Viberzi, Vraylar, Xuriden, Zurampic
OVERVIEW
A continuing upward trend for the annual number of CDER’s novel new drug approvals necessarily relies on a corresponding increase in the number of drug applications submitted for approval. During the past decade, submissions of applications for NMEs and novel new BLAs by the pharmaceutical and biotechnology industry have remained relatively stable.
More important than the quantity of novel new drugs approved in 2015 are the qualities of the new drugs the pharmaceutical industry has developed and the important new roles these drugs are serving to advance medical care.
Also noteworthy is the efficiency with which most of these drugs were reviewed and approved. CDER used a variety of expedited development and review regulatory tools in an effort to help speed these drugs to market.
In all cases, while striving for efficiency of review and approval of applications for new drugs, CDER maintains its rigorous standards for demonstration of effectiveness and safety in the process.
Drug Designation Summary
First-in-Class
Drugs with a new and unique mechanism for treating a medical condition
Orphan Drugs
Drugs approved for small populations of patients with rare diseases
Breakthrough
A drug with preliminary clinical evidence demonstrating that it may result in substantial improvement on at least one clinically significant endpoint over available therapies.
Fast Track
Drugs that can treat unmet medical needs
Priority Review
A drug is given a priority review if there is potential to provide a significant advance in existing medical care. Drugs assigned priority review under CDER’s Priority Review Voucher program are not included in this summary.
Accelerated Approval
Early approval based on markers that predict a reasonable benefit, with more testing to confirm clinical benefit after approval
PDUFA Goal Date
The goal date for application review determined by the Prescription Drug User Fee Act (PDUFA).
First Cycle
Drugs that were approved without request for additional information that could delay approval and lead to another cycle of review
First Approved in U.S.
Drugs that were approved in the United States before approval in other country
Qualified Infectious Disease Program Designation
A drug with particular promise can be designated as a Qualified Infectious Disease Product (QIDP) by authority of the Generating Antibiotics Incentives Now Act (GAIN Act)