Pharmaceutical Substances - Version 4.14

The version 4.14 of Pharmaceutical Substances was launched in May 2023.

This release describes 19 novel, innovative active pharmaceutical ingredients, some of which have been granted breakthrough therapy, fast track, and orphan drug designation by the FDA.

The release also covers updates to the GABA(A) BZ Site receptor agonist Medazepam and the vasopressin (AVP) V1 receptor ligand Terlipressin, originally launched by Ferring for the treatment of bleeding of esophageal varices. Terlipressin received fast track designation for the treatment of refractory ascites due to advanced liver cirrhosis.

Promising new antitumor drugs were approved, including Belzutifan, which was granted breakthrough therapy designation in the U.S. for the treatment of adult patients with von Hippel-Lindau (VHL) disease requiring therapy for associated renal cell carcinoma (RCC). Other approved drugs include the epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) antagonist Mobocertinib, the HGFR (MET; c-Met) inhibitor Tepotinib, and Adagrasib, a small-molecule inhibitor of the GTPase KRAS used as breakthrough therapy of non-small cell lung cancer. Futibatinib, an irreversible FGFR inhibitor, was approved for the treatment of advanced or metastatic cholangiocarcinoma (CCA), and Olutasidenib¸ an isocitrate dehydrogenase-1 (mIDH1) inhibitor, was approved for therapy of acute myeloid leukemia. Pacritinib, an orally available kinase inhibitor with specificity for JAK2, FLT3, IRAK1 and CSF1R, has been approved for the treatment of myelofibrosis.

Five new drugs received fast track designation, including Deucravacitinib, a first-in-class, oral allosteric inhibitor of tyrosine kinase 2 (TYK2), and Tapinarof, an aryl hydrocarbon receptor (AhR) modulating agent, both for plaque psoriasis. Abbvie’s small-molecule antagonist of the calcitonin gene-related peptide receptor (CGRPR), Atogepant, was approved as a novel acting anti-migraine agent, and Ganaxolone was approved as a gamma-aminobutyric acid [GABA(A)] receptor-modulating synthetic analogue of allopregnanolone. Lenacapavir, an oral, long-acting small-molecule inhibitor of the HIV-1 capsid protein p24, received breakthrough therapy designation for the treatment of HIV-1 infection.

Furthermore, this release includes Difelikefalin, a kappa opioid receptor long-acting agonist metalloproteinase inhibitor for the treatment of uremic pruritus in chronic kidney disease and dialysis. Shionogi´s 3CL protease inhibitor Ensitrelvir is included for the therapy of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Mitapivat, a small-molecule activator of the pyruvate kinase isozyme R (PKLR), is approved as a treatment against pyruvate kinase deficiency. The prostaglandin E2 Receptor EP2 subtype (PTGER2; EP2) agonist Omidenepag isopropyl in included for glaucoma treatment. Oteseconazole, a lanosterol 14-alphademethylase inhibitor developed by Mycovia, is included as a treatment for candidal vaginal infections. The H+/K+-ATPase inhibitor Vonoprazan, approved for therapy in adults for the healing of all grades of erosive esophagitis (EE), and Ursodoxicoltaurine, approved as an antiamyloidogenic agent for treatment of gallstones are also included.

Prof. Axel Kleemann, Prof. Bernhard Kutscher, Dr. Dietmar Reichert, Dr. Martin Bossart