Resmetirom: First Approval.

Resmetirom (Rezdiffra™) is an oral thyroid hormone receptor-ß (THR-ß) agonist being developed by Madrigal Pharmaceuticals, Inc., to target the key underlying causes of metabolic dysfunction associated steatohepatitis (MASH) [previously known as nonalcoholic steatohepatitis (NASH)]. In March 2024, resmetirom was approved for use (under accelerated approval) in conjunction with diet and exercise for the treatment of adults with noncirrhotic NASH with moderate to advanced liver fibrosis (consistent with stages F2 to F3 fibrosis) in the USA. Resmetirom is also under regulatory review in the EU for the treatment of MASH/NASH. This article summarizes the milestones in the development of resmetirom leading to this first approval for the treatment of adults with MASH/NASH.

Cefepime/Enmetazobactam: First Approval.

Cefepime/enmetazobactam (EXBLIFEP®), an intravenous (IV) antibacterial fixed-dose combination of a 4th generation cephalosporin and an extended-spectrum ß-lactamase (ESBL) inhibitor, is being developed by Allecra Therapeutics and ADVANZ PHARMA for the treatment of infections caused by multi-drug-resistant (MDR) Gram-negative bacteria. In February 2024, cefepime/enmetazobactam was approved in the USA for use in adults with complicated urinary tract infections (cUTI) including pyelonephritis, caused by susceptible strains of Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Proteus mirabilis, and Enterobacter cloacae complex. In March 2024, cefepime/enmetazobactam was approved in the EU for use in adults for the treatment of cUTI, including pyelonephritis, and hospital-acquired pneumonia, including ventilator associated pneumonia, and the treatment of patients with bacteraemia occurring in association with or suspected to be associated with any of these infections. This article summarizes the milestones in the development of cefepime/enmetazobactam leading to this first approval for the treatment of adults with infections caused by MDR Gram-negative bacteria.

Lifileucel: First Approval.

Lifileucel (AMTAGVI™), a one-time autologous T cell therapy derived and expanded from tumour-infiltrating lymphocytes (TIL) from a patient's own tumour, is being developed by Iovance Biotherapeutics, Inc. for the treatment of cancer. Lifileucel was granted accelerated approval based on objective response rate (ORR) in February 2024 in the USA for use in adult patients with unresectable or metastatic melanoma previously treated with a PD-1 blocking antibody, and if BRAF V600 mutation positive, a BRAF inhibitor with or without a MEK inhibitor. This article summarizes the milestones in the development of lifileucel leading to this first approval for the treatment of patients with unresectable or metastatic melanoma who have progressed on or after prior anti-PD-1/L1 therapy and targeted therapy.

Lebrikizumab: First Approval.

Lebrikizumab (Ebglyss®) is a subcutaneous recombinant humanized IgG4 anti-IL-13 monoclonal antibody developed by Almirall S.A. and Eli Lilly and Company for the treatment of atopic dermatitis (AD). In November 2023, lebrikizumab was approved in the EU for the treatment of moderate-to-severe AD in adults and adolescents 12 years and older with a body weight of at least 40 kg who are candidates for systemic therapy. Lebrikizumab was approved for the same indication in the UK in December 2023 and in Japan in January 2024. Lebrikizumab is under regulatory review for the treatment of AD in the USA, Switzerland and Australia. This article summarizes the milestones in the development of lebrikizumab leading to this first approval for AD.

Berdazimer Topical Gel, 10.3%: First Approval.

Berdazimer topical gel, 10.3% (ZELSUVMI™) is a nitric oxide (NO) releasing topical gel developed by Novan Inc. (a Ligand Pharmaceuticals company) for the treatment of molluscum contagiosum (MC). Novan has used their proprietary NO-based technology platform (NITRICIL™), which stores gaseous NO species on large polymers, in the development of berdazimer topical gel, 10.3%. In January 2024, berdazimer topical gel, 10.3% was approved for the topical treatment of MC in adult and paediatric patients 1 year of age and older in the USA. This article summarizes the milestones in the development of berdazimer topical gel, 10.3% leading to this first approval for the treatment of MC.

Nirogacestat: First Approval.

Nirogacestat (OGSIVEO™) is an oral, selective, reversible, small molecule γ-secretase inhibitor developed by SpringWorks Therapeutics, Inc. γ-Secretase is a multi-subunit protease complex that cleaves multiple transmembrane protein complexes, including Notch and membrane-bound B-cell maturation antigen (BCMA). Inhibition of γ-secretase may result in growth inhibition of tumour cells overexpressing Notch, and preservation of membrane-bound BCMA may increase target density for BCMA-targeted therapy. In November 2023, nirogacestat was approved in the USA for use in adult patients with progressing desmoid tumours who require systemic treatment. This article summarizes the milestones in the development of nirogacestat leading to this first approval for the systemic treatment of desmoid tumours.

Cantharidin Topical Solution 0.7%: First Approval.

Cantharidin (YCANTH™) is a proprietary drug-device combination product containing a formulation of cantharidin 0.7% topical solution (a vesicant naturally derived from blister beetles) delivered via a single-use applicator that has been developed by Verrica Pharmaceuticals Inc. for the treatment of molluscum contagiosum and is also being developed for the treatment of warts. In July 2023, YCANTH™ (cantharidin 0.7% topical solution) was approved for the topical treatment of molluscum contagiosum in adult and pediatric patients 2 years of age and older in the USA. This article summarizes the milestones in the development of cantharidin 0.7% topical solution leading to this first approval for the topical treatment of molluscum contagiosum in adult and pediatric patients 2 years of age and older.

Vamorolone: First Approval.

Vamorolone (AGAMREE®) is an oral, selective, dissociative corticosteroid developed by ReveraGen BioPharma and Santhera Pharmaceuticals for the treatment of patients with muscular dystrophy. Vamorolone was approved in October 2023 for the treatment of Duchenne muscular dystrophy (DMD) in patients 2 years of age and older in the USA and received a positive opinion in the EU in October 2023 for the treatment of DMD in patients 4 years of age and older. This article summarizes the milestones in the development of vamorolone leading to this first approval for DMD.

Gepirone Extended-Release: First Approval.

Gepirone HCL extended-release (gepirone ER; EXXUA™), an oral, selective serotonin (5HT)1A receptor agonist formulated for once-daily administration, has been developed by Fabre-Kramer Pharmaceuticals, Inc. for the treatment of psychiatric disorders, including major depressive disorder (MDD). In September 2023, gepirone ER was approved in the USA for the treatment of adults with MDD. This article summarizes the milestones in the development of gepirone ER leading to this first approval for the treatment of adults with MDD.

Iruplinalkib: First Approval.

Iruplinalkib (Trade name: ®; Code name: WX-0593), a highly selective oral anaplastic lymphoma kinase (ALK) and c-ros oncogene 1 (ROS1) tyrosine kinase inhibitor (TKI), is being developed by Qilu Pharmaceutical Co., Ltd. for the treatment of ALK-positive (ALK+) or ROS1-positive (ROS1+) non-small cell lung cancer (NSCLC). In June 2023, iruplinalkib was approved in China for the treatment of patients with locally advanced or metastatic ALK+ NSCLC who have progressed after prior crizotinib therapy or are intolerant to crizotinib. This article summarizes the milestones in the development of iruplinalkib leading to this first approval for the treatment of patients with locally advanced or metastatic ALK+ NSCLC.

Momelotinib: First Approval.

Momelotinib (OJJAARA) is an oral Janus kinase 1 and 2 (JAK1/JAK2) and activin A receptor, type I (ACVR1) inhibitor that has been developed for the treatment of myelofibrosis (MF). In September 2023, momelotinib was approved in the USA for the treatment of intermediate or high-risk MF, including primary MF or secondary MF [post-polycythemia vera (PV) and post-essential thrombocythemia (ET)], in adults with anemia. This article summarizes the milestones in the development of momelotinib leading to this first approval for MF.

Tafolecimab: First Approval.

Tafolecimab (SINTBILO®), a subcutaneously administered anti-proprotein convertase subtilisin/kexin type 9 enzyme (PCSK9) monoclonal antibody, is being developed by Innovent for the treatment of hypercholesterolemia and mixed hyperlipidemia. Tafolecimab was approved in August 2023 in China as an adjunct to diet, in combination with a statin or statin with other low-density lipoprotein cholesterol (LDL-C)-lowering therapies, for the treatment of adults with primary hyperlipidemia [including heterozygous familial hypercholesterolemia (HeFH) and non-familial hypercholesterolemia (non-FH)] and mixed dyslipidemia who have failed to achieve LDL-C goals despite moderate or higher doses of statins, to reduce LDL-C, total cholesterol (TC), and apolipoprotein B (ApoB) levels. This article summarizes the milestones in the development of tafolecimab leading to this first approval for the treatment of adults with primary hyperlipidemia and mixed dyslipidemia.

Talquetamab: First Approval.

Talquetamab (talquetamab-tgvs; TALVEY®), a humanized, bispecific G-protein coupled receptor family C group 5 member D (GPRC5D)-directed CD3 T-cell engager, is being developed by Janssen for the treatment of multiple myeloma (MM). In early August 2023, talquetamab was granted accelerated approval in the USA for the treatment of adults with relapsed or refractory MM (RRMM) and in late August 2023, talquetamab was granted conditional marketing authorisation in the EU for the treatment of adult patients with RRMM. This article summarizes the milestones in the development of talquetamab leading to this first approval for RRMM.

Equecabtagene Autoleucel: First Approval.

Equecabtagene autoleucel (Fucaso®), an autologous anti-B cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR)-T cell therapy that uses lentivirus as a gene vector to transfect autologous T cells, is being developed by IASO Biotechnology and Innovent Biologics, Inc. for the treatment of multiple myeloma (MM) and autoimmune diseases of the nervous system, including neuromyelitis optica spectrum disorder (NMOSD). Equecabtagene autoleucel was granted conditional approval in China in June 2023 for the treatment of adults with relapsed or refractory MM (RRMM) who have progressed after ≥ 3 lines of therapy (≥ 1 proteasome inhibitor and an immunomodulator). This article summarizes the milestones in the development of equecabtagene autoleucel leading to this first approval in patients with RRMM who have progressed after multiple lines of therapy.

Sulbactam/Durlobactam: First Approval.

Sulbactam/durlobactam (XACDURO®), is a co-packaged antibacterial product that has been developed by Entasis Therapeutics Inc. for the treatment of infections caused by Acinetobacter baumannii-calcoaceticus complex (ABC). Coadministration of durlobactam (a ß-lactamase inhibitor with potent activity against a broad range of serine ß-lactamases) with sulbactam (an established class A ß-lactamase inhibitor with antibacterial activity against A. baumannii) prevents sulbactam degradation by ABC-produced ß-lactamases. In May 2023, sulbactam/durlobactam was approved in the USA for use in patients 18 years of age and older for the treatment of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP) caused by susceptible isolates of ABC. This article summarizes the milestones in the development of sulbactam/durlobactam leading to this first approval for the treatment of infections caused by ABC.

Sovateltide: First Approval.

Sovateltide (Tycamzzi™), a highly selective endothelin-B receptor agonist and synthetic analog of endothelin-1, is being developed by Pharmazz, Inc. as a neural progenitor cell therapeutic agent for the treatment of acute cerebral ischemic stroke (ACIS), hypoxic-ischemic encephalopathy (HIE), spinal cord injuries and Alzheimer's disease. In May 2023, sovateltide was approved in India for the treatment of cerebral ischemic stroke within 24 h of stroke onset. This article summarizes the milestones in the development of sovateltide leading to this first approval for use in patients with ACIS.

Mirikizumab: First Approval.

Mirikizumab (Omvoh®), a humanized IgG4 anti-human IL-23p19 monoclonal antibody, is being developed by Eli Lilly and Company Ltd for the treatment of ulcerative colitis and Crohn's disease. Mirikizumab was approved in March 2023 in Japan for use as induction and maintenance therapy in patients with moderate to severe ulcerative colitis who have an inadequate response to conventional therapy or therapies and is the first IL-23p19 inhibitor to be approved for this indication. Mirikizumab was granted a positive opinion in the EU in March 2023 for the treatment of adult patients with moderately to severely active UC who have had an inadequate response with, lost response to, or were intolerant to either conventional therapy or a biologic treatment. This article summarizes the milestones in the development of mirikizumab leading to this first approval for use in ulcerative colitis.

Concizumab: First Approval.

Concizumab (Alhemo™), a subcutaneously administered humanised monoclonal IgG4 antibody against tissue factor pathway inhibitor (TFPI), binds to the Kunitz-2 domain of TFPI and prevents TFPI from binding to activated Factor X. Concizumab is being developed by Novo Nordisk for the treatment of hemophilia A and B with and without inhibitors. In March 2023, concizumab was approved in Canada for the treatment of adolescent and adult patients (12 years of age or older) with hemophilia B who have FIX inhibitors and require routine prophylaxis to prevent or reduce the frequency of bleeding episodes. This article summarizes the milestones in the development of concizumab leading to this first approval for the treatment of hemophilia B.