Editorial pubs.acs.org/chemneuro
Novel Drug Approvals in 2015 and Thus Far in 2016
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molecular entities (NMEs) under New Drug Applications (NDAs), or as new therapeutics biologics under a related Biologics License Application (BLA). This number of approvals is 2015 is larger than normal, despite submitted applications
ast year, the United States Food and Drug Administration (FDA) and its Center for of Drug Evaluation and Research (CEDR) released their fifth annual novel drug summary.1,2 In 2015, CDER approved 45 novel drugs (Table 1), as new Table 1. Novel Drugs Approved by the FDA in 20151,2 drug name Zurampic Uptravi Bridion Alecensa Kanuma Empliciti Portrazza Ninlaro Daralex Tagrisso Cotellic Genoya
active ingredient
approval date
indication
12/22/2015 12/22/2015 12/15/2015 12/11/2015 12/08/2015 11/30/2015 11/24/2015 11/20/2015 11/16/2015 11/13/2015 11/10/2015 11/05/2015
high blood uric acid levels due to gout pulmonary hypertension reverse effects of neuromuscular drugs ALK-positive lung cancer lysomal acid lipase deficiency multiple mylenoma advanced nonsmall cell lung carcinoma multiple mylenoma multiple mylenoma nonsmall cell lung carcinoma melanoma combo with vemurafenib HIV-1 infection
Nucala Strensiq Yondelis Veltassa Praxbind Aristada Tresiba Lonsurf Vraylar Xuriden Varubi Repatha Addyi
lesinurad selexipag sugammadex alectinib seblipase alfa elotuzumab necitumumab ixazomib daratumumab osimertinib cobimetinib fixed dose combo of elvitegravir, emtricitiabine, and tenofovir alafenamide mepolizumab asfotase alfa trabectedin patiromer idarucizumab aripiprazole lauroxil isulin degludec injection trifluridine and tipiracil cariprazine uridine triacetate rolapitant evolocumab flibanserin
11/04/2015 10/23/2015 10/23/2015 10/21/2015 10/06/2015 10/06/2015 09/25/2015 09/22/2015 09/17/2015 09/04/2015 09/02/2015 08/27/2015 08/18/2015
Dalinza Odomzo Praluent Rexulti Enresto Orkambi Kengreal Viberzi Kybella Corlanor Cholbam Unituxin Cresemaba Avycaz Farydak Lenvima Ibrance Natpara Cosentyx
daclastavir sonidegib alirocumab brexpiprazole sacubitril/valsartan lumacaftor 200 mg/ivacaftor 125 mg canegrelor eluxadoline deoxycholic acid ivabrandine cholic acid dinutuximab isavuconazonium sulfate ceftazidine-avibactum panobinostat lenvatinib palbociclib parathyroid hormone secukinumab
07/24/2015 07/24/2015 07/24/2015 07/10/2015 07/07/2015 07/02/2015 06/22/2015 05/27/2015 04/29/2015 04/15/2015 03/17/2015 03/10/2015 03/06/2015 02/25/2015 02/23/2015 02/13/2015 02/03/2015 01/21/2015 01/21/2015
asthma perinatal, infantile, and juvenile onset hypophosphatasia soft-tissue sarcomas hyperkalemia reverse Pradaxa’s blood-thinning effect schizophrenia diabetes colorectal cancer schizophrenia hereditary orotic aciduria emesis high cholesterol hypoactive sexual desire disorder in premenopausal women hepatitis C virus basal cell carcinoma high cholesterol schizophrenia heart failure cystic fibrosis blood clots irritable bowel syndrome submental fat heart failure bile acid synthesis disorders pediatric neuroblastoma invasive aspergillosis intra-abdominal infection multiple mylenoma differentiated thyroid cancer metastatic breast cancer hypocalacemia plaque psoriasis
Published: September 21, 2016 © 2016 American Chemical Society
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DOI: 10.1021/acschemneuro.6b00254 ACS Chem. Neurosci. 2016, 7, 1175−1176
ACS Chemical Neuroscience
Editorial
remaining constant. Between 2006 and 2014, CEDR approvals averaged 28 novel drugs per year. While 2006−2012 saw approvals in the 20s, the last 2 years saw approvals peak into the 40s. Thus far in 2016 (as of August 2016), CEDR has approved 16 novel drugs, suggesting lower approvals in 2016.1,2 In 2015, key approvals focused on cancer (the majority), cardiovascular, cystic fibrosis, irritable bowel syndrome, urinary tract infection, and chronic hepatitis C. CNS therapeutics were also represented, with three schizophrenia drugs approved in 2015: Rexulti, Aristada, and Vraylar. CEDR operates on a platform of impact, innovation, predictability, and access.2 In terms of impact, of the 45 drugs approved in 2015, 16 (36%) were identified as first-in-class, with novel mechanisms of action and include Addyl, Daralex, Kanuma, Praxbind, Bridion, Corlanor, Cosentyx, Empliciti, Nucala, Strensiq, Entresto, Orkambi, Unittuxin, Ibrance, Praluent, and Xuriden. Of these, CEDR identified three as particularly noteworthy first-in-class products: Bridion (reverse post surgical blockade of anesthesia), Praxbind (reverse anticoagulant effects of the blood thinner dabigatran), and Ibrance (for advanced metastatic breast cancer).1,2 Notable among the 2015 approvals were the 21 drugs (47%) approved to treat rare or “orphan diseases”, defined as diseases affecting less than 200 000 Americans. This is really significant, as smaller patient populations often lack medications for their conditions due to market pressures. Drugs approved here include Alecensa, Cresemba, Farydak, Natpra, Portrazza, Strensiq, Uptravi, Cholbam, Daralex, Kanuma, Ninlaro, Praxbind, Tagrisso, Xuriden, Cotellic, Empliciti, Lenvima, Orkambi, Repatha, Unituxin, and Yondelis.1,2 One noteworthy example to point out is Unituxin, a new agent to treat high-risk neuroblastoma (a CNS tumor), for which little therapy exists for children. Another in the pediatric space is Strensiq, a new long-term enzyme replacement therapy for childhood-onset hypophosphatasia, an often fatal bone disease.1,2 In 2015, CEDR employed a diverse array of strategies to expedite the path of innovative medicines to the market, including Fast Track, Breakthrough, Priority Review, and Accelerated Approval.2 If a drug has the potential to address an unmet medical need, CEDR can designate these as Fast Track. This designation accelerates drug development by increasing communication with the FDA and allowing review of portions of the NDA in advance of the full application. Last year, 14 (31%) of the 45 approved drugs were designated as Fast Track: Avycaz, Daralex, Lonsurf, Tagrisso, Corlanor, Enteresto, Orkambi, Viberzi, Cotellic, Genvoya, Portrazza, Daklinza, Kanuma, and Strensiq.1,2 CEDR also designated 10 (22%) new drugs as Breakthroughs, meaning preliminary clinical evidence demonstrates that drug treatment results in a substantial improvement in at least one clinically relevant end point.2 This designation offers all the advantages of Fast Track, but also more intensive FDA guidance to help shorten development time and deliver the drug to patients. For 2015, the following drugs fell into this catergory: Alecensa, Orkambi, Daralex, Praxbind, Empliciti, Strensiq, Ibrance, Tagrisso, Kanuma, and Xuriden.1,2 Another tool CEDR employs is Priority Review, wherein a drug that could potentially offer a significant advance is reviewed within 6 months, rather than the standard 10 months.2 Twenty-four novel drugs (53%) received this status in 2015: Alecsensa, Cresemba, Ibrance, Strensiq, Avycaz, Daklinza, Kanuma, Tagrisso, Bridion, Daralex, Lenvima, Unituxin, Cholbam, Emlpiciti, Ninlaro, Viberzi, Corlanor, Entresto, Orkambi, Xuriden, Cotellic, Farydak, Praxbind, and Yondelis.1,2
Finally, drugs targeting a serious or life-threatening illness that offer clear benefits over existing therapies may fall into the FDA’s Accelerated Approval program. Last year, CEDR approved six (13%) novel drugs into this program: Alecensa, Daralex, Farydak, Ibrance, Tagrisso, and Praxbind.1,2 Overall in 2015, CEDR employed the use of one of these four for expedited development, and review for 27 (53%) of all novel drugs approved. Importantly, for patients, CEDR approved 87% (39 of 45) of novel drugs on the “first cycle” without requests for additional information, greatly accelerating medicines to needy patients. Moreover, 64% (29 of 45) of novel drugs in 2015 were approved by the FDA in the Unites States first, before approval in any other country.1,2 As mentioned earlier, the pace of new drug approval appears slower in 2016, with only 16 approved by August. However, 2016 witnessed the April 29, 2016 approval of Nuplazid (pimavanserin), a novel agent to treat the psychotic symptoms (hallucinations and delusions) in some Parkinson’s patients, an unmet medical need in this patient population. Next year, we will detail the full list and designations of novel drugs approved in 2016.1,2 Clearly, CEDR and the FDA are using all the tools at their disposal to expedite the development and approval of novel medicineswonderful news for both patients and drug developers. Thus, 2015 was not only a great year for approvals, but also, as highlighted recently, a great year for global pharmaceutical products, with $954.1 billion in sales (a 9.5% increase over 2014).3
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Craig W. Lindsley, Editor-in-Chief AUTHOR INFORMATION
Notes
Views expressed in this editorial are those of the author and not necessarily the views of the ACS.
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REFERENCES
(1) For information, see http://www.centerwatch.com/druginformation/fda-approved-drugs/. (2) For information, see http://www.fda.gov/Drugs/ DevelopmentApprovalProcess/DrugInnovation/ucm483775.htm. (3) Lindsley, C. W. (2016) 2015: A New Impact Factor for ACS Chemical Neuroscience and New Topline Data for Global Pharmaceutical Products. ACS Chem. Neurosci., 7, 842−843.
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DOI: 10.1021/acschemneuro.6b00254 ACS Chem. Neurosci. 2016, 7, 1175−1176
