The Pharmaceutical Industry in 2023: An Analysis of FDA Drug Approvals from the Perspective of Molecules

Abstract

With the COVID-19 pandemic behind us, the U.S. Food and Drug Administration (FDA) has approved 55 new drugs in 2023, a figure consistent with the number authorized in the last five years (53 per year on average). Thus, 2023 marks the second-best yearly FDA harvest after 2018 (59 approvals) in all the series. Monoclonal antibodies (mAbs) continue to be the class of drugs with the most approvals, with an exceptional 12, a number that makes it the most outstanding year for this class. As in 2022, five proteins/enzymes have been approved in 2023. However, no antibody-drug conjugates (ADCs) have been released onto the market. With respect to TIDES (peptides and oligonucleotides), 2023 has proved a spectacular year, with a total of nine approvals, corresponding to five peptides and four oligonucleotides. Natural products continue to be the best source of inspiration for drug development, with 10 new products on the market. Three drugs in this year's harvest are pegylated, which may indicate the return of pegylation as a method to increase the half-lives of drugs after the withdrawal of peginesatide from the market in 2013. Following the trends in recent years, two bispecific drugs have been authorized in 2023. As in the preceding years, fluorine and/or N-aromatic heterocycles are present in most of the drugs. Herein, the 55 new drugs approved by the FDA in 2023 are analyzed exclusively on the basis of their chemical structure. They are classified as the following: biologics (antibodies, proteins/enzymes); TIDES (peptide and oligonucleotides); combined drugs; pegylated drugs; natural products; nitrogen aromatic heterocycles; fluorine-containing molecules; and other small molecules.

Keywords: TIDES; antibodies; biologics; chemical entities; fluorine-based drugs; imaging; natural products; new chemical entities; oligonucleotides; peptides.

Figure 1

Drugs (new chemical entities and biologics) approved by the FDA in the last 25 years. Adapted with permission from ref. [2]. Copyright 2023, copyright MDPI [1,2,3].

Figure 2

Structure of zilucoplan (blue, non-proteinogenic amino acids; red, γ-amide bond).

Figure 3

Structure of motixafortide.

Figure 4

Structure of rezzayo.

Figure 5

Structure of trofinetide.

Figure 6

Structure of flotufolastat F-18.

Figure 7

Structure of nedosiran.

Figure 8

Structure of tofersen.

Figure 9

Structure of eplontersen.

Figure 10

Structure of avacincaptad pegol.

Figure 11

Structures of sulbactam and durlobactam contained in Xacduro^TM.

Figure 12

Structures of nirmatrelvir and ritonavir contained in Paxlovid^TM.

Figure 13

Structures of taurolidine and heparin contained in Defencath^TM.

Figure 14

Structures of bexagliflozin and sotagliflozin.

Figure 15

Structures of zuranolone, agamree, betulin*—the main component of birch triterpenes—and omaveloxolone.

Figure 16

Structures of perfluorhexyloctane, repotrectinib, lotilaner, pirtobrutinib, leniolisib, etrasimod, nirogacestat, and fezolinetant, all F-containing APIs.

Figure 17

Structures of quizartinib, momelotinib, zavegepant, gepirone, sparsentan, capivasertib, iptacopan, fruquintinib, and ritlecitinib, extended polyheterocyclics with N as major heteroatom.

Figure 18

Structures of palovarotene, daprodustat, and elacestrant.

Figure 19

Drugs approved by the FDA in 2023 classified on the basis of chemical structure (drugs can belong to more than one class) Adapted with permission from ref. [1]. Copyright 2022, copyright MDPI.

Figure 20

Similar to Figure 19 for 2022, taken with permission from reference [2]. Copyright 2023, copyright MDPI.

Figure 21

Similar to Figure 19 for 2021, taken with permission from reference [7]. Copyright 2022, MDPI.