Naunyn-Schmiedeberg's Archives of Pharmacology · 4 authors, 3 centres
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In 2022, the FDA approved 37 new molecular entities, a decline from the 53 and 50 approvals in 2020 and 2021, respectively, and below the 10-year average of 43 per year. Despite the lower total, 54% of approvals were first-in-class drugs, and 54% were designated as orphan drugs, continuing trends toward innovation and rare disease focus. Oncology and rare diseases remained the dominant therapeutic areas, and biologics accounted for the highest share of approvals to date.
**Background:** The U.S. Food and Drug Administration (FDA) approved 37 new molecular entities in 2022, a decrease from 53 in 2020 and 50 in 2021, and below the rolling 10-year average of 43 approvals per year. This annual review, continuing analyses from 2020 and 2021, assesses the degree of pharmacological innovation among these newly approved compounds. The authors note that discussing best-in-class or best-in-indication comparisons, as well as drug pricing, is beyond the scope of the article.
**Methods:** The analysis is based on the FDA's list of new molecular entities approved in 2022. Vaccines, generics, biosimilars, and already-approved drugs receiving additional indications or novel formulations were excluded. Newly approved drug combinations were included only if at least one component was a novel entity. The focus on FDA approvals is for reference purposes and does not imply a judgment on other regulatory agencies.
**Key Results:** The 37 approved drugs span multiple therapeutic areas. In oncology, notable approvals include nivolumab/relatlimab for unresectable or metastatic melanoma (first-in-class dual immunotherapy), tebentafusp for HLA-A*02:01-positive uveal melanoma (first-in-class bispecific fusion protein), and lutetium (177Lu) vipivotide tetraxetan for PSMA-positive metastatic castration-resistant prostate cancer. Other oncology approvals include futibatinib for FGFR2 fusion-positive cholangiocarcinoma, tremelimumab (in combination with durvalumab) for hepatocellular carcinoma, teclistamab for relapsed/refractory multiple myeloma, mirvetuximab soravtansine for folate receptor alpha-positive ovarian cancer, adagrasib for KRAS G12C-mutated NSCLC, mosunetuzumab for relapsed/refractory follicular lymphoma, pacritinib for myelofibrosis with thrombocytopenia, and olutasidenib for IDH1-mutant acute myeloid leukemia. In hematology, sutimlimab was approved for cold agglutinin disease, mitapivat for pyruvate kinase deficiency, and eflapegrastim for febrile neutropenia. Neurology approvals include daridorexant for insomnia, ganaxolone for CDKL5 deficiency disorder, sodium phenylbutyrate-taurursodiol for ALS, vutrisiran for hereditary transthyretin-mediated amyloidosis, and ublituximab for relapsing multiple sclerosis. Metabolic/cardiovascular/endocrine approvals include mavacamten for obstructive hypertrophic cardiomyopathy, tirzepatide for glycemic control, teplizumab to delay onset of stage 3 type 1 diabetes, and terlipressin for hepatorenal syndrome. Dermatology approvals include daxibotulinumtoxinA for glabellar lines, abrocitinib for atopic dermatitis, tapinarof for plaque psoriasis, spesolimab for generalized pustular psoriasis, deucravacitinib for plaque psoriasis, anacaulase for burn eschar removal, and oteseconazole for recurrent vulvovaginal candidiasis. Other approvals include vonoprazan/amoxicillin/clarithromycin for Helicobacter pylori, olipudase alfa for acid sphingomyelinase deficiency, faricimab for neovascular age-related macular degeneration and diabetic macular edema, omidenepag for open-angle glaucoma, gadopiclenol as a contrast agent, and lenacapavir for multi-drug-resistant HIV-1. First-in-class drugs accounted for 54% of approvals, next-in-class for 46%. Orphan drugs constituted 54% of approvals. Accelerated pathways were frequently used: 32% fast track, 35% breakthrough therapy, 57% priority review, and 16% accelerated approval. Biologics accounted for the highest share to date, with small molecules at 51%, antibodies at 27%, and peptides at 19%.
**Clinical Implications:** The lower number of approvals in 2022 may reflect COVID-19 pandemic effects on clinical trial recruitment and manufacturing inspections, though similar fluctuations have occurred historically. The high proportion of first-in-class (54%) and orphan (54%) drugs indicates continued industry focus on innovation and rare diseases, incentivized by the Orphan Drug Act and Rare Diseases Act. Oncology remains the largest therapeutic area (29% of approvals). The increasing share of biologics, including bispecific antibodies and antibody-drug conjugates, represents a continuing trend. The frequent use of accelerated approval pathways suggests regulatory incentives are shaping development pipelines, though first-in-class status does not always translate to superior clinical benefit over existing treatments.