The Pharmaceutical Industry in 2021. An Analysis of FDA Drug Approvals from the Perspective of Molecules

Abstract

Similar to last year, 2021 will be remembered for the COVID-19 pandemic. Although five vaccines have been approved by the two most important drug regulatory agencies, namely the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA), the pandemic has still not been brought under control. However, despite the context of a global pandemic, 2021 has been an excellent year with respect to drug approvals by the FDA. In 2021, 50 drugs have been authorized, making it the fourth-best year after 2018 (59 drugs) and 1996 and 2020 (53 each). Regarding biologics, 2021 has been the third-best year to date, with 14 approvals, and it has also witnessed the authorization of 36 small molecules. Of note, nine peptides, eight monoclonal antibodies, two antibody-drug conjugates, and two oligonucleotides have been approved this year. From them, five of the molecules are pegylated and three of them highly pegylated. The presence of nitrogen aromatic heterocycles and/or fluorine atoms are once again predominant among the so-called small molecules. This report analyzes the 50 new drugs approved in 2021 from a chemical perspective, as it did for those authorized in the previous five years. On the basis of chemical structure alone, the drugs that received approval in 2021 are classified as the following: biologics (antibodies, antibody-drug conjugates, enzymes, and pegylated proteins); TIDES (peptide and oligonucleotides); combined drugs; natural products; nitrogen aromatic heterocycles; fluorine-containing molecules; and other small molecules.

Keywords: API; CBER; CDER; COVID-19; TIDES; antibodies; antibody-drug conjugate; biologics; chemical entities; drug discovery; fluorine-based drugs; natural products; nitrogen aromatic heterocycles; oligonucleotides; pegylation; peptides; small molecules.

Figure 1

Drugs (New Chemical Entities and Biologics) approved by the FDA in the last 25 years [1,5,6,7,8].

Figure 2

Structure of tisotumab vedotin-tftv.

Figure 3

Structure of loncastuximab tesirine-lpyl.

Figure 4

Structure of pegcetacoplan.

Figure 5

Structure of dasiglucagon.

Figure 6

Structure of vosoritide.

Figure 7

Structure of voclosporin. In red, the difference with cyclosporin is marked: an extra carbon atom linked by a double bond.

Figure 8

Structure of difelikefalin.

Figure 9

Structures of melphalan flufenamide and odevixibat.

Figure 10

Structure of piflufolastat F-18.

Figure 11

Structure of Casimersen.

Figure 12

Structure of inclisiran.

Figure 13

Structure of the combination drugs: Nextstellis^TM (drospirenone/estetrol); Lybalvi^TM (olanzapine/samidorphan); Cabenuva^TM (cabotegravir/rilpivirine); and Azstarys^TM (serdexmethylphenidate/dexmethylphenidate).

Figure 14

Structures of maribavir and ibrexafungerp, both drugs inspired by natural products.

Figure 15

Structures of atogepant and avacopan, both of which contain trifluoromethyl moieties.

Figure 16

Structures of umbralisib, asciminib, sotorasib, belzutifan, and vericiguat.

Figure 17

Structures of mobocertinib, tepotinib, infigratinib, trilaciclib, tivozanib, belumosudil, fosdenopterin, finerenone, fexinidazole, and pafolacianine, all of which contain nitrogen aromatic heterocycles.

Figure 18

Structure of ponesimod, maralixibat chloride, and viloxazine.

Figure 19

Drugs approved by the FDA in 2021 classified on the basis of chemical structure (drugs can belong to more than a class).