Vaborbactam (formerly RPX7009) is a new beta-lactamase inhibitor based on a cyclic boronic acid pharmacophore. Vaborbactam is a highly active beta-lactamase inhibitor that restores activity of meropenem and other beta-lactam antibiotics in beta-lactamase-producing bacteria, particularly KPC-producing CRE. Meropenem in combination with vaborbactam (VABOMERE) is indicated for the treatment of patients 18 years and older with complicated urinary tract infections including pyelonephritis caused by designated susceptible bacteria. The vaborbactam component of VABOMERE is a non-suicidal beta-lactamase inhibitor that protects meropenem from degradation by certain serine beta-lactamases such as Klebsiella pneumoniae carbapenemase (KPC). Vaborbactam does not have any antibacterial activity. Vaborbactam does not decrease the activity of meropenem against meropenem-susceptible organisms.

Ribociclib, also known as LEE011, is an orally available cyclin-dependent kinase (CDK) inhibitor targeting cyclin D1/CDK4 and cyclin D3/CDK6 cell cycle pathway, with potential antineoplastic activity. CDK4/6 inhibitor LEE011 specifically inhibits CDK4 and 6, thereby inhibiting retinoblastoma (Rb) protein phosphorylation. Inhibition of Rb phosphorylation prevents CDK-mediated G1-S phase transition, thereby arresting the cell cycle in the G1 phase, suppressing DNA synthesis and inhibiting cancer cell growth. Overexpression of CDK4/6, as seen in certain types of cancer, causes cell cycle deregulation. Ribociclib is in phase III clinical trials by Novartis for the treatment of postmenopausal women with advanced breast cancer. Phase II clinical trials are also in development for the treatment of liposarcoma, ovarian cancer, fallopian tube cancer, peritoneum cancer, endometrial cancer, and gastrointestinal cancer. Preregistration for Breast cancer (First-line therapy, Combination therapy, Late-stage disease) in the USA (PO) in November 2016.

Deutetrabenazine (trade name Austedo) is a vesicular monoamine transporter 2 (VMAT2) inhibitor indicated for the treatment of chorea associated with Huntington’s disease. The drug was developed by Auspex Pharmaceuticals and is being commercialized by Teva Pharmaceuticals. Deutetrabenazine is a deuterated derivative of tetrabenazine. The incorporation of deuterium in place of hydrogen at the sites of primary metabolism results in metabolic clearance being slowed, allowing less frequent dosing and better tolerability.

Naldemedine (Symproic) is an opioid antagonist indicated for the treatment of opioid-induced constipation (OIC) in adult patients with chronic non-cancer pain. Naldemedine is an opioid antagonist with binding affinities for mu-, delta-, and kappa-opioid receptors. Naldemedine functions as a peripherally-acting mu-opioid receptor antagonist in tissues such as the gastrointestinal tract, thereby decreasing the constipating effects of opioids. Naldemedine is a derivative of naltrexone to which a side chain has been added that increases the molecular weight and the polar surface area, thereby reducing its ability to cross the blood-brain barrier (BBB). Naldemedine is also a substrate of the P-glycoprotein (P-gp) efflux transporter. Based on these properties, the CNS penetration of naldemedine is expected to be negligible at the recommended dose levels, limiting the potential for interference with centrally-mediated opioid analgesia. Naldemedine was approved in 2017 in both the US and Japan for the treatment of Opioid-induced Constipation.

Ertugliflozin (PF-04971729) is a potent and selective sodium-dependent glucose cotransporter 2 (SGLT2) inhibitor incorporating a unique dioxa-bicyclo[3.2.1]octane (bridged ketal) ring system. SGLT2 has become an important therapeutic target and several SGLT2-selective inhibitors are either approved or in clinical development for the management of blood glucose in patients with type 2 diabetes. Ertugliflozin demonstrated robust urinary glucose excretion in rats and an excellent preclinical safety profile. It was announced that FDA and EMA filing acceptances of three marketing applications for ertugliflozin-containing medicines for adults with type 2 diabetes.

Etelcalcetide (formerly velcalcetide, trade name Parsabiv) is a calcimimetic drug for the treatment of secondary hyperparathyroidism in patients undergoing hemodialysis. Etelcalcetide was approved (trade name Parsabiv) for the treatment of secondary hyperparathyroidism (HPT) in adult patients with chronic kidney disease (CKD) on hemodialysis in February, 2017. Etelcalcetide is a synthetic peptide calcium-sensing receptor agonist. It allosterically modulates the calcium-sensing receptor (CaSR). Etelcalcetide binds to the CaSR and enhances activation of the receptor by extracellular calcium. Activation of the CaSR on parathyroid chief cells decreases PTH secretion.

Telotristat (telotristat etiprate) is an ethyl ester prodrug which is hydrolyzed to its active moiety LP-778902 both in vivo and in vitro. Telotristat etiprate is an orally bioavailable, small-molecule, tryptophan hydroxylase (TPH) inhibitor. It is the first investigational drug in clinical studies to target TPH, an enzyme that triggers the excess serotonin production within metastatic neuroendocrine tumor (mNET) cells leading to carcinoid syndrome. Unlike existing treatments of carcinoid syndrome which reduce the release of serotonin outside tumor cells, telotristat etiprate reduces serotonin production within the tumor cells. By specifically inhibiting serotonin production telotristat may provide patients with more control over their disease. Telotristat etiprate has received Fast Track and Orphan Drug designation from the U.S. Food and Drug Administration and has been granted priority review by the FDA with a Prescription Drug User Fee Act (PDUFA) target action date of February 28, 2017.

Safinamide (FCE 26743, NW 1015, PNU 151774, PNU 151774E, trade name Xadago) combines potent, selective, and reversible inhibition of MAO-B with blockade of voltage-dependent Na+ and Ca2+ channels and inhibition of glutamate release. Safinamide is under development with Newron, Zambon and Meiji Seika Pharma for the treatment of Parkinson's disease. Safinamide has been launched in the EU, Iceland and Liechtenstein. Safinamide was well tolerated and safe in the clinical development program that demonstrated the amelioration of motor symptoms and OFF phenomena by safinamide when combined with dopamine agonists or levodopa.

Neratinib (HKI-272) is a pan-HER inhibitor, this irreversible tyrosine kinase inhibitor binds and inhibits the tyrosine kinase activity of epidermal growth factor receptors, EGFR (or HER1), HER2 and HER4, which leads to reduced phosphorylation and activation of downstream signaling pathways. Neratinib is a modified form of the discontinued compound pelitinib, and was originally being develoAdditionally, phase II development of oral neratinib as a neoadjuvant therapy for breast cancer, as a second-line therapy for non-small cell lung cancer, and for other solid tumours is also in progress in numerous countries worldwide. ped by Wyeth (later Pfizer). Oral neratinib is awaiting approval as an extended adjuvant therapy for breast cancer in the EU and in the US. Blocking HER2 function by a small molecule kinase inhibitor, such as neratinib, represents an attractive alternate strategy for the growth inhibition of HER2-positive tumours.

Secnidazole (trade names Flagentyl, Sindose, Solosec) is a nitroimidazole derivative used to in the treatment of amoebiasis and bacterial vaginosis. Secnidazole and other 5-nitroimidazole drugs enter micro-organisms by passive diffusion and undergo activation by reduction of the 5-nitro group. In anaerobic micro-organisms, such as Trichomonas, Giardia and Entamoeba spp., this intracellular reduction occurs via the pyruvate ferredoxin oxidoreductase complex and results in a concentration gradient across the cell membrane which, in tum, enhances transport of the parent drug into the cell. Because the electron affinity of the 5-nitroimidazoles is greater than that of reduced ferredoxin, the drug interrupts the normal electron flow. Aerobic micro-organisms have a more positive redox potential (i.e. are more efficient electron acceptors) than secnidazole and other 5-nitroimidazoles, which explains the selective toxicity of these drugs against anaerobic microorganisms. DNA is the intracellular target of the Secnidazole and other 5-nitroimidazoles. Secnidazole and other 5-nitroimidazoles possess selective activity against many anaerobic Gram-positive and Gram-negative bacteria and protozoa. In general, secnidazole and metronidazole were approximately equipotent in activity against Bacteroides fragilis, Trichomonas vaginalis, and Entamoeba histolytica, in in vitro studies. Secnidazole is rapidly and completely absorbed after oral administration. Plasma drug concentrations are linear over the therapeutic dose range of 0.5 to 2g. The tolerability profile of secnidazole does not differ markedly from other 5-nitroimidazoles. The most commonly reported adverse events in clinical trials involved the gastrointestinal tract (nausea, vomiting, glossitis, anorexia, epigastric pain and a metallic taste) and occurred in 2 to 10% of patients. A headache and dizziness were experienced by about 2% of patients. The drug was equally well tolerated in adults and children, and no adverse event required therapeutic intervention or treatment withdrawal.