Oxaliplatin (brand name Eloxatin), a new generation of platinum derivatives discovered by Prof Kidani in 1976 at Nagoya University in Japan, was licensed-in and developed by Debiopharm. Eloxatin is typically administered in combination with fluorouracil and leucovorin for the adjuvant treatment of stage III colon cancer and for the treatment of advanced carcinoma of the colon or rectum. Oxaliplatin undergoes nonenzymatic conversion in physiologic solutions to active derivatives via displacement of the labile oxalate ligand. Several transient reactive species are formed, including monoaquo and diaquo 1,2-diaminocyclohexane (DACH) platinum, which covalently bind with macromolecules. Both inter- and intrastrand Pt-DNA crosslinks are formed. Crosslinks are formed between the N7 positions of two adjacent guanines (GG), adjacent adenine-guanines (AG), and guanines separated by an intervening nucleotide (GNG). These crosslinks inhibit DNA replication and transcription. Cytotoxicity is cell-cycle nonspecific.

Nabiximols (USAN, trade name Sativex) is a specific extract of Cannabis that was approved as a botanical drug in the United Kingdom in 2010 as a mouth spray to alleviate neuropathic pain, spasticity, overactive bladder, and other symptoms of multiple sclerosis. Nabiximols is an oromucosal spray of a formulated extract of the cannabis sativa plant that contains the principal cannabinoids tetrahydrocannabinol (THC) and cannabidiol (CBD) as well as specific minor cannabinoids and other non-cannabinoid components. THC is a partial agonist and can block activation by other ligands of both cannabinoid receptors (CBR). THC effects include analgesia, short-term memory loss, muscle relaxation, antiemesis, appetite stimulation, and anti-inflammatory activity. CBD acts on CBR and TRPV1, while also inhibiting reuptake and hydrolysis of anandamide N-arachidonylethanolamine (AEA). CBD effects include anticonvulsant, muscle relaxant, anxiolytic, neuroprotective, antioxidant, anti-inflammatory, immunomodulatory and anti-psychotic activity. CBD modulates some of the more undesirable psychological adverse effects of THC through both pharmacokinetic and pharmacodynamic effects. Each 100 μl spray contains: 2.7 mg of THC and 2.5 mg of CBD. Nabiximols was approved in other European countries and Canada.

Semustine is a methylated derivative of carmustine with potent antineoplastic activity. As an alkylating agent, semustine forms covalent linkages with nucleophilic centers in DNA, causing depurination, base-pair miscoding, strand scission, and DNA-DNA cross-linking, which may result in cytotoxicity. Semustine is primarily used to treat brain tumors, colorectal tumors, lymphomas, and stomach cancer.

Tirzepatide (Mounjaro™) is a single molecule that combines dual agonism of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors. Tirzepatide is a GIP receptor and GLP-1 receptor agonist. It is a 39-amino-acid modified peptide with a C20 fatty diacid moiety that enables albumin binding and prolongs the half-life. Tirzepatide selectively binds to and activates both the GIP and GLP-1 receptors, the targets for native GIP and GLP-1. Tirzepatide enhances first- and second-phase insulin secretion, and reduces glucagon levels, both in a glucose-dependent manner. GIP also plays a role in nutrient and energy metabolism, while GLP-1 also delays gastric emptying, supresses appetite and improves satiety. Eli Lilly is developing tirzepatide for the treatment of type 2 diabetes mellitus (T2DM), obesity, cardiovascular disorders in T2DM, heart failure, non-alcoholic steatohepatitis, obstructive sleep apnoea and for reducing mortality/morbidity in obesity. In May 2022, tirzepatide received its first approval in the USA to improve glycaemic control in adults with T2DM, as an adjunct to diet and exercise. Tirzepatide is in phase III development for heart failure, obesity and cardiovascular disorders in T2DM, and in phase II development for non-alcoholic steatohepatitis. Tirzepatide can also be used off-label for treating obesity. It is currently implemented as a second-line diabetes medication, similar to GLP-1 medications like semaglutide. It is a once-a-week subcutaneous injectable medication with incremental dose increases.

Terlipressin (Glypressin) is indicated for the treatment of bleeding oesophageal varices and in some countries for the treatment of hepatorenal syndrome type 1. It is a prodrug and is converted to the lysine vasopressin in the circulation after the N-triglycyl residue is cleaved by endothelial peptidases. This results in a ‘slow release’ of the vasoactive lysine vasopressin. Terlipressin exerts its action by activating V1a, V1b and V2 vasopressin receptors. On September 14, 2022, the FDA granted approval to terlipressin (Terlivaz) for the treatment of adults hospitalized with hepatorenal syndrome with rapid reduction in kidney function (HRS-1). Prior to the approval, no approved treatment for this condition existed in the United States.

Dasiglucagon (Zegalogue®) is an antihypoglycaemic agent being developed by Zealand Pharma for the treatment of hypoglycaemia, type 1 diabetes mellitus (T1DM) management and congenital hyperinsulinism. Dasiglucagon is a glucagon receptor agonist, which increases blood glucose concentration by activating hepatic glucagon receptors, thereby stimulating glycogen breakdown and release of glucose from the liver. Hepatic stores of glycogen are necessary for dasiglucagon to produce an antihypoglycemic effect. In March 2021, dasiglucagon received its first approval in the USA for the treatment of severe hypoglycaemia in paediatric and adult patients with diabetes aged 6 years and above. Dasiglucagon, a glucagon analogue, is available as a single-dose autoinjector or prefilled syringe for subcutaneous injection.

Vosoritide (VOXZOGO®; BMN-111) is a modified recombinant human C-type natriuretic peptide (CNP) analogue, being developed by BioMarin Pharmaceutical for the treatment of achondroplasia. Achondroplasia is caused by a gain-of-function mutation in the fibroblast growth factor receptor 3 gene (FGFR3), which is a negative regulator of bone growth. Vosoritide acts to restore chondrogenesis through its binding to natriuretic peptide receptor B (NPR-B), resulting in the inhibition of downstream signalling pathways of the overactive FGFR3 gene. Vosoritide was approved in August 2021 in the EU for the treatment of achondroplasia in patients aged ≥ 2 years whose epiphyses are not closed; the diagnosis of achondroplasia should be confirmed by appropriate genetic testing. In November 2021, Voxzogo was also approved by FDA to improve growth in children with achondroplasia.

Semaglutide (trade name Ozempic) is a pharmaceutical drug in development by a Danish company Novo Nordisk for the treatment of type 2 diabetes. Semaglutide is a once-daily glucagon-like peptide-1 analog that differs to others by the presence of an acyl group with a steric diacid at Lys26 and a large synthetic spacer and modified by the presence of a α-aminobutyric acid in position 8 which gives stability against the dipeptidylpeptidase-4. Semaglutide is a GLP-1 analogue with 94% sequence homology to human GLP-1. Semaglutide acts as a GLP-1 receptor agonist that selectively binds to and activates the GLP-1 receptor, the target for native GLP-1. GLP-1 is a physiological hormone that has multiple actions on glucose, mediated by the GLP-1 receptors. The principal mechanism of protraction resulting in the long half-life of semaglutide is albumin binding, which results in decreased renal clearance and protection from metabolic degradation. Furthermore, semaglutide is stabilized against degradation by the DPP-4 enzyme. Semaglutide reduces blood glucose through a mechanism where it stimulates insulin secretion and lowers glucagon secretion, both in a glucose-dependent manner. Thus, when blood glucose is high, insulin secretion is stimulated and glucagon secretion is inhibited. The mechanism of blood glucose lowering also involves a minor delay in gastric emptying in the early postprandial phase.

X-396 (Ensartinib) is a novel, potent anaplastic lymphoma kinase (ALK) small molecule tyrosine kinase inhibitor (TKI) with additional activity against MET, ABL, Axl, EPHA2, LTK, ROS1 and SLK. Ensartinib has demonstrated activity in ALK treatment naïve and previously treated patients and has a generally well tolerated safety profile. Ensartinib is currently in a global phase 3 trial in ALK positive non-small cell lung cancer (NSCLC) patients. The phase 1/2 clinical findings support the preclinical results that the use of ensartinib may result in favorable therapeutic outcomes in patients with ALK NSCLC, including patients with CNS metastases. In this study, ensartinib was generally well tolerated with the most common adverse event being a rash.

X-396 (Ensartinib) is a novel, potent anaplastic lymphoma kinase (ALK) small molecule tyrosine kinase inhibitor (TKI) with additional activity against MET, ABL, Axl, EPHA2, LTK, ROS1 and SLK. Ensartinib has demonstrated activity in ALK treatment naïve and previously treated patients and has a generally well tolerated safety profile. Ensartinib is currently in a global phase 3 trial in ALK positive non-small cell lung cancer (NSCLC) patients. The phase 1/2 clinical findings support the preclinical results that the use of ensartinib may result in favorable therapeutic outcomes in patients with ALK NSCLC, including patients with CNS metastases. In this study, ensartinib was generally well tolerated with the most common adverse event being a rash.