Small molecules accounted for 42, or 71%, of the 59 new molecule entities (NMEs) approved by the FDA in 2018, continuing a recent trend in which small molecules have accounted for roughly three-quarters of NME approvals. Which small-molecules and companies contributed to the NME Class of 2018?

Small molecules leading the NME pack

In 2018, the US Food and Drug Administration’s (FDA) Center for Drug Evaluation and Research (CDER) approved a record-high 59 new molecular entities (NMEs), surpassing the previous record of 53 NME approvals in 1996 and the 46 NMEs approved in 2017. Small molecules dominated in NME approvals in 2018 with 42 (71% of NME approvals) compared to 17 biologic-based NME approvals (29% of NME approvals), which included one antibody drug conjugate (ADC) (see Table I at end of article; NDA approval denotes small molecule).

This product mix in 2018 is consistent with NME approvals in 2017 and with recent years with the exception of 2016. In 2017, small-molecule NME approvals accounted for 74% of new drug approvals (see Table II at end of article) and biologics 26%. Between 2010 and 2015, small molecules accounted for between 71% and 81% of NME approvals. The exception was in 2016, when a lower number of NME approvals occurred with 22 NME approvals, which included 13 small-molecule NME approvals or 59%.

Big Pharma and small molecules

Of the 42 small-molecule NME approvals in 2018, 18 or 43% were from the large pharmaceutical companies, and 57% of small-molecule approvals in 2018 were from small to mid-sized companies (see Table I at end of article; NDA approval denotes small molecule).

Among the large pharmaceutical companies, Pfizer led with four NME approvals in 2018, all of which were small molecules. These were: Daurismo (glasdegib) for treating newly diagnosed acute myeloid leukemia (AML) in adult patients; Lorbrena (loratinib) for treating patients with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer; Talzenna (talazoparib) for treating locally advanced or metastatic breast cancer patients with a germline BRCA mutation; and Vizimpro (dacomitinib) for treating metastatic non-small-cell lung cancer.

Fourteen of the large pharmaceutical companies each had one small-molecule NME approval in 2018.

AbbVie received approval for Orilissa (elagolix sodium) for treating moderate-to-severe pain associated with endometriosis. Allergan got the FDA nod for Seysara (sarecycline) for treating inflammatory lesions of non-nodular moderate to severe acne vulgaris in patients nine years of age and older. Astellas received approval for Xospata (gilteritinib) for treating relapsed or refractory acute myeloid leukemia, and AstraZeneca received approval for Lokelma (sodium zirconium cyclosilicate) for treating hyperkalemia (high potassium levels). Eli Lilly and Company got the FDA nod for Olumiant (baricitinib) for treating moderately to severely active rheumatoid arthritis. Also, through its pending $8-billion acquisition of Loxo Oncology, Lilly will gain another small-molecule NME approval from 2018, Vitrakvi (larotrectinib), an anti-cancer drug.

Gilead Sciences received approval for a fixed-dose combination HIV drug, Biktarvy (bictegravir, embitcitabine, and tenofovir alafenamide), and GlaxoSmithKline received approval for Krintafel (tafenoquine), an anti-malaria drug. Johnson & Johnson’s Janssen Pharmaceutical got the FDA nod for Erleada (apalutamid) for treating non-metastatic, castration-resistant prostate cancer. Merck & Co. also gained approval of an HIV drug, Pifeltro (doravirine).

Mylan, although largely a generic-drug company, did get a NME approval in 2018, for its small-molecule, Yupelri (revefenacin) for treating chronic obstructive pulmonary disease (COPD). Novartis, through its acquisition of Advanced Accelerator Applications in 2018, received approval for the radiopharmaceutical, Lutathera (lutetium Lu 177 dotatate) for treating gastroenteropancreatic neuroendocrine tumors, a type of cancer that affects the pancreas or gastrointestinal tract.

Shire, which was acquired by Takeda in January 2019, received approval for Motegrity (prucalopride) for treating idiopathic constipation. Shionogi received approval for Mulpleta (lusutrombopag) for treating thrombocytopenia in adult patients with chronic liver disease who are scheduled to undergo a procedure, and Roche’s Genentech received approval for Xofluza (baloxavir marboxil), an antiviral medicine.