Top Selling (2026) Small Molecule Orphan Drugs: A Journey into Their Chemistry

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2023 Jan 21

PMID 36674441

Authors

Davide Benedetto Tiz

Luana Bagnoli

Ornelio Rosati

Francesca Marini

Luca Sancineto

Claudio Santi

Affiliations

Soon will be listed here.

Abstract

This review describes, from a chemical point of view, the top "blockbuster" small molecule orphan drugs according to their forecasted sales in 2026. Orphan drugs are intended for the treatment, prevention, or diagnosis of a rare disease or condition. These molecules are mostly addressed to the treatment of rare forms of cancer. The respiratory and central nervous systems represent other common therapeutic subcategories. This work will show how the orphan drugs market has significantly grown and will account for a consistent part of prescriptions by 2026.

Citing Articles

Highlights on U.S. FDA-approved halogen-containing drugs in 2024.

Ali S, Tian X, Meccia S, Zhou J Eur J Med Chem. 2025; 287:117380.

PMID: 39947048 PMC: 11846695. DOI: 10.1016/j.ejmech.2025.117380.

FDA Approvals of Biologics in 2022.

Martins A, Albericio F, de la Torre B Biomedicines. 2023; 11(5).

PMID: 37239105 PMC: 10216111. DOI: 10.3390/biomedicines11051434.

References

Sellers W, Fisher D . Apoptosis and cancer drug targeting. J Clin Invest. 1999; 104(12):1655-61. PMC: 409892. DOI: 10.1172/JCI9053. View

Przepiorka D, Luo L, Subramaniam S, Qiu J, Gudi R, Cunningham L . FDA Approval Summary: Ruxolitinib for Treatment of Steroid-Refractory Acute Graft-Versus-Host Disease. Oncologist. 2020; 25(2):e328-e334. PMC: 7011641. DOI: 10.1634/theoncologist.2019-0627. View

Aronson J . Rare diseases and orphan drugs. Br J Clin Pharmacol. 2006; 61(3):243-5. PMC: 1885017. DOI: 10.1111/j.1365-2125.2006.02617.x. View

Nocco S, Andriano T, Bose A, Chilov M, Godwin K, Dranitsaris G . Ibrutinib-associated dermatologic toxicities: A systematic review and meta-analysis. Crit Rev Oncol Hematol. 2022; 174:103696. DOI: 10.1016/j.critrevonc.2022.103696. View

Byrd J, Harrington B, OBrien S, Jones J, Schuh A, Devereux S . Acalabrutinib (ACP-196) in Relapsed Chronic Lymphocytic Leukemia. N Engl J Med. 2015; 374(4):323-32. PMC: 4862586. DOI: 10.1056/NEJMoa1509981. View

Menear K, Adcock C, Boulter R, Cockcroft X, Copsey L, Cranston A . 4-[3-(4-cyclopropanecarbonylpiperazine-1-carbonyl)-4-fluorobenzyl]-2H-phthalazin-1-one: a novel bioavailable inhibitor of poly(ADP-ribose) polymerase-1. J Med Chem. 2008; 51(20):6581-91. DOI: 10.1021/jm8001263. View

Ridley K, Condren M . Elexacaftor-Tezacaftor-Ivacaftor: The First Triple-Combination Cystic Fibrosis Transmembrane Conductance Regulator Modulating Therapy. J Pediatr Pharmacol Ther. 2020; 25(3):192-197. PMC: 7134581. DOI: 10.5863/1551-6776-25.3.192. View

Sala M, Jain M . Tezacaftor for the treatment of cystic fibrosis. Expert Rev Respir Med. 2018; 12(9):725-732. DOI: 10.1080/17476348.2018.1507741. View

Salem A, Agarwal S, Dunbar M, Nuthalapati S, Chien D, Freise K . Effect of Low- and High-Fat Meals on the Pharmacokinetics of Venetoclax, a Selective First-in-Class BCL-2 Inhibitor. J Clin Pharmacol. 2016; 56(11):1355-1361. DOI: 10.1002/jcph.741. View

10.

Lin Q, Meloni D, Pan Y, Xia M, Rodgers J, Shepard S . Enantioselective synthesis of Janus kinase inhibitor INCB018424 via an organocatalytic aza-Michael reaction. Org Lett. 2009; 11(9):1999-2002. DOI: 10.1021/ol900350k. View

11.

Asbury C . The Orphan Drug Act. The first 7 years. JAMA. 1991; 265(7):893-7. View

12.

Simoes C, Almeida Z, Costa D, Jesus C, Cardoso A, Almeida M . A novel bis-furan scaffold for transthyretin stabilization and amyloid inhibition. Eur J Med Chem. 2016; 121:823-840. DOI: 10.1016/j.ejmech.2016.02.074. View

13.

Laselva O, Bartlett C, Gunawardena T, Ouyang H, Eckford P, Moraes T . Rescue of multiple class II CFTR mutations by elexacaftor+tezacaftor+ivacaftor mediated in part by the dual activities of elexacaftor as both corrector and potentiator. Eur Respir J. 2020; 57(6). PMC: 8209484. DOI: 10.1183/13993003.02774-2020. View

14.

Patel V, Balakrishnan K, Bibikova E, Ayres M, Keating M, Wierda W . Comparison of Acalabrutinib, A Selective Bruton Tyrosine Kinase Inhibitor, with Ibrutinib in Chronic Lymphocytic Leukemia Cells. Clin Cancer Res. 2016; 23(14):3734-3743. PMC: 5491371. DOI: 10.1158/1078-0432.CCR-16-1446. View

15.

Markham A, Dhillon S . Acalabrutinib: First Global Approval. Drugs. 2017; 78(1):139-145. DOI: 10.1007/s40265-017-0852-8. View

16.

Jiang J, Ma X, Ouyang D, Williams 3rd R . Emerging Artificial Intelligence (AI) Technologies Used in the Development of Solid Dosage Forms. Pharmaceutics. 2022; 14(11). PMC: 9694557. DOI: 10.3390/pharmaceutics14112257. View

17.

Pan Z, Scheerens H, Li S, Schultz B, Sprengeler P, Burrill L . Discovery of selective irreversible inhibitors for Bruton's tyrosine kinase. ChemMedChem. 2006; 2(1):58-61. DOI: 10.1002/cmdc.200600221. View

18.

Fiedorczuk K, Chen J . Molecular structures reveal synergistic rescue of Δ508 CFTR by Trikafta modulators. Science. 2022; 378(6617):284-290. PMC: 9912939. DOI: 10.1126/science.ade2216. View

19.

Burger J . Bruton Tyrosine Kinase Inhibitors: Present and Future. Cancer J. 2019; 25(6):386-393. PMC: 7083517. DOI: 10.1097/PPO.0000000000000412. View

20.

Haydl A, Xu K, Breit B . Regio- and enantioselective synthesis of N-substituted pyrazoles by rhodium-catalyzed asymmetric addition to allenes. Angew Chem Int Ed Engl. 2015; 54(24):7149-53. DOI: 10.1002/anie.201501758. View