2018 was a banner year for the US Food and Drug Administration (FDA), with 59 new drugs approved by the Center for Drug Evaluation and Research (CDER), including 19 first-in-class agents, 34 novel drugs for rare diseases, and a record seven biosimilars. The 59 drug approvals in 2018 are the most in more than 10 years; 46 new drugs were approved in 2017, and 22 were approved in 2016. Between 2009 and 2017, the CDER averaged about 33 novel drug approvals per year. Of the 59 novel drugs approved by the CDER, 43 (73%) had priority review, 24 (41%) were fast tracked, and 14 (24%) were designated as breakthrough therapies. Decisions on all 59 drugs were generally completed by or before their goal dates. 2018 saw the first drug derived from marijuana to clear the FDA, with approvalof a purified formulation of cannabidiol (Epidiolex oral solution, GW Pharmaceuticals) for the treatment of seizures related to two rare forms of epilepsy — Lennox-Gastaut syndrome and Dravet syndrome — for patients older than 2 years. The FDA also approved a second new medication for Dravet syndrome — stiripentol (Diacomit, Biocodex). This drug and Epidiolex are the only FDA-approved treatments for patients with Dravet syndrome. Other notable drug approvals for rare or orphan diseases affecting 200,000 or fewer Americans include the following: Migalastat (Galafold, Amicus Therapeutics) for Fabry disease caused by a genetic mutation amenable to treatment with the drug as determined on the basis of in vitro assay data. Migalastat is the first oral medicine for Fabry disease and the first new therapy approved to treat this rare disease in the United States in more than 15 years. Burosumab (Crysvita, Ultragenyx Pharmaceutical Inc), the first drug approved to treat adults and children aged 1 year and older with X-linked hypophosphatemia, a rare, inherited, progressive form of rickets. Pegvaliase (Palynziq, BioMarin Pharmaceutical Inc), for adults with the rare genetic disease phenylketonuria (PKU). Palynziq is the first approvedenzyme substitution therapy to target the underlying cause of PKU. Amifampridine (Firdapse, Catalyst Pharmaceuticals), a potassium channel blocker and the first approved treatment of Lambert-Eaton myasthenic syndrome in adults. Cenegermin (Oxervate, Dompé Farmaceutici SpA) for neurotrophic keratitis, a rare and serious disease affecting the cornea of the eye. Elapegademase (Revcovi, Leadiant Biosciences) for adults and children with adenosine deaminase severe combined immune deficiency (ADA-SCID), a rare metabolic disorder that causes severe immunodeficiency and is life-threatening without treatment. Notable first-in-class agents include lofexidine hydrochloride (Lucemyra, US WorldMeds), the first nonopioid drug approved to help reduce opioid withdrawal symptoms and to facilitate abrupt discontinuation of opioids in adults. Also approved was ibalizumab (Trogarzo, Theratechnologies Inc), a new type of antiretroviral medication for adults with multidrug-resistant HIV-1. The FDA also approved three new injectable drugs for the prevention of migraine in adults: erenumab (Aimovig, Amgen/Novartis), fremanezumab(Ajovy, Teva), and galcanezumab (Emgality, Eli Lilly and Co). All three belong to a new class of drugs, calcitonin gene–related peptide receptor antagonists. For young women, the FDA approved segesterone acetate and ethinyl estradiol (Annovera, the Population Council, Inc), the first vaginal ring contraceptive that can be used for an entire year to prevent pregnancy. 2018 also saw the first FDA approval in nearly 20 years of a new antiviral flu treatment that has a novel mechanism of action. Baloxavir marboxil tablets (Xofluza, Shionogi) are for the treatment of acute uncomplicated influenza in people aged 12 years and older who have been symptomatic for no more than 48 hours. Oncology Notable approvals in the field of oncology/hematology include the following: Duvelisib (Copiktra, Verstem Oncology) for relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma. Duvelisib is an oral inhibitor of phosphoinositide 3–kinase (PI3K) and is the first to act as a dual inhibitor of PI3K-delta and PI3K-gamma. Glasdegib (Daurismo, Pfizer) for newly diagnosed acute myeloid leukemia(AML) in patients aged 75 years or older or those who have comorbidities that disallow use of intensive chemotherapy. Glasdegib belongs to a class of drugs known as oral smoothened inhibitors and is for use in combination with low-dose cytarabine. Ivosidenib (Tibsovo, Agios Pharmaceuticals) for adults with relapsed or refractory AML who harbor isocitrate dehydrogenase–1 (IDH1) mutations, and the companion RealTime IDH1 Assay (Abbott Laboratories). Gilteritinib (Xospata, Astellas Pharma) for adults with FLT3 mutation–positive relapsed or refractory AML. Avatrombopag (Doptelet, AkaRx Inc), a second-generation oral thrombopoietin receptor agonist to increase platelet counts in adults with thrombocytopenia and chronic liver disease who are to undergo a planned medical or dental procedure. Tagraxofusp (Elzonris, Stemline Therapeutics), the first approved treatment for blastic plasmacytoid dendritic cell neoplasm, an aggressive form of blood cancer that has a proclivity for skin and leukemic involvement. Apalutamide (Erleada, Janssen), the first agent for nonmetastatic, castration-resistant prostate cancer. This approval marked the first time the FDA used metastasis-free survival as the primary endpoint in its decision making. Cemiplimab (Libtayo, Regeneron Pharmaceuticals) for metastatic cutaneous squamous cell carcinoma (CSCC) or locally advanced, unresectable CSCC (another first). Moxetumomab pasudotox (Lumoxiti, AstraZeneca) for adults with relapsed or refractory hairy cell leukemia who have received at least two prior lines of therapy. The agent is a CD22-directed cytotoxin or immunotoxin and is the first-in-class treatment for patients with this rare cancer. Seven Biosimilars Since 2015, the FDA has approved 16 biosimilars for nine different reference products. Seven new biosimilars cleared the FDA in 2018: Fulphila (pegfilgrastim-jmdb), and Udenyca (pegfilgrastim-cbqv), respectively the first and second biosimilars to Neulasta (Amgen). Herzuma (trastuzumab-abtr), the second biosimilar to Herceptin(Genentech). Hyrimoz (adalimumab-adaz), the third biosimilar to Humira (AbbVie). Nivestym (filgrastim-aafi), the second biosimilar to Neupogen (Amgen). Retacrit (epoetin alfa-epbx), the first biosimilar to Epogen/Procrit (Amgen). Truxima (rituximab-abbs), the first biosimilar to Rituxan (Genentech). "Biosimilars have great potential for both patients and the entire health care system," CDER Director Janet Woodcock, MD, said in the report Advancing Health Through Innovation: 2018 New Drug Therapy Approvals, released January 7. "As patents and exclusivity protections for biologics expire in the United States, we can expect many more biosimilars to be submitted for approval. More products on the market means greater competition that can lead to increased access to therapies and lower costs to patients," said Woodcock. Source
