Fexinidazole is an antiparasitic drug, which is in the phase III of clinical trial for the treatment of Human African Trypanosomiasis, and in the phase II for the treatment Disease, Chagas and Visceral Leishmaniosis. However, for the Visceral Leishmaniosis, studies were terminated, due to lack of efficacy. Fexinidazole rapidly metabolized to two active metabolites, a sulfone and a sulfoxide, which prolong the pharmacological action of parent drug. These metabolites retaine trypanocidal activity but are less effective in nifurtimox-resistant lines, which can lead to the potential danger in the use of fexinidazole as a monotherapy.

Fostemsavir (BMS-663068) is an investigational attachment inhibitor with a unique mechanism of action. It is a prodrug of temsavir, which binds to HIV envelope glycoprotein 120 (gp120), thereby preventing viral attachment to the host CD4 cell surface receptor. In the absence of effective binding of HIV gp120 with the host CD4 receptor, HIV does not enter the host cell. Because fostemsavir has a novel mechanism of action, the drug should have full activity against HIV strains that have developed resistance to other classes of antiretroviral medications. In a phase 2b study of treatment-experienced individuals, fostemsavir appeared to be well tolerated. Phase 3 studies are ongoing.

Vibegron is a selective beta 3 adrenergic receptor (β3AR) agonist that is being developed in Japan jointly by Kyorin Pharmaceutical Co., Ltd and Kissei Pharmaceutical Co., Ltd and in other regions worldwide (except in several other Asian countries) by Urovant Sciences for the treatment of overactive bladder (OAB). Vibegron potently activates human b3AR and increases cAMP levels, with an EC50 of 1.1 nM. Based on results from Japanese phase III trials, vibegron received approval in Japan in September 2018 for this indication. Vibegron, an active ingredient of Beova® Tablets, is a novel once-daily oral treatment for overactive bladder (OAB), acts selectively on the bladder's β3-adrenergic receptor, relaxes the bladder and enhances the urine collection, and consequently improves the symptoms of urgency, urinary frequency and urge urinary incontinence associated with OAB. On December 23, 2020 the FDA approved vibegron (Gemtesa) for the treatment of adult patients with overactive bladder (OAB) with symptoms of urge urinary incontinence (UUI), urgency, and urinary frequency.

Elexacaftor (VX-445) is a next-generation cystic fibrosis transmembrane conductance regulator (CFTR) corrector. It received FDA approval in October 2019 in combination with tezacaftor and ivacaftor as the combination product Trikafta for the treatment of cystic fibrosis in patients aged ≥ 12 years who have ≥ 1 F508del mutation in the CFTR gene. Trikafta™ has been developed by Vertex Pharmaceuticals Inc. to treat patients with the most common cystic fibrosis mutation (F508del). Its use has been associated with statistically significant and/or clinically meaningful improvements in lung function and respiratory-related quality of life compared with comparator regimens (placebo or ivacaftor/tezacaftor) in multinational phase II and III studies. Elexacaftor and tezacaftor bind to different sites on the CFTR protein and have an additive effect in facilitating the cellular processing and trafficking of select mutant forms of CFTR (including F508del-CFTR) to increase the amount of CFTR protein delivered to the cell surface compared to either molecule alone. Ivacaftor potentiates the channel open probability (or gating) of the CFTR protein at the cell surface.

Upadacitinib (ABT-494) is a Janus kinase 1 (JAK1) inhibitor currently being developed by AbbVie for the treatment of rheumatoid arthritis (RA), Crohn’s disease, ulcerative colitis, atopic dermatitis, and psoriatic arthritis. It is also being investigated as a potential treatment for people with active ankylosing spondylitis (AS). Currently, upadacitinib is being evaluatedin six global phase III studies in RA and twophase III studies in psoriatic arthritis (PsA), inaddition to phase II studies in Crohn’s disease and atopicdermatitis and a combined phase II/III study inulcerative colitis. Upadacitinib is a potent and selective Janus kinase (JAK) 1 inhibitor with an IC50 of 43 nM.

LEFAMULIN is a pleuromutilin antibiotic under development for the treatment of community-acquired bacterial pneumonia, as well as acute bacterial skin and skin structure infections. It inhibits bacterial protein synthesis by binding to the peptidyl transferase center of the 50S ribosome, resulting in the cessation of bacterial growth.

Tenapanor is an inhibitor of the sodium-proton (Na(+)/H(+)) exchanger NHE3 and reduces sodium absorption in the GI tract, thus increasing intestinal fluid. Ardelyx has completed Phase 3 development of tenapanor for the treatment of irritable bowel syndrome with constipation (IBS-C) and submitted a new drug application to the U.S. Food and Drug Administration for the treatment of patients with IBS-C. In addition, tenapanor successfully completed phase III clinical trial for the treatment of hyperphosphatemia in people with end-stage renal disease who are on dialysis and RDX013, a potassium secretagogue program for the potential treatment of high potassium, or hyperkalemia, a problem among certain patients with kidney and/or heart disease.

Lemborexant is a dual orexin receptor antagonist, which inhibits orexin by binding competitively to two subtypes of orexin receptors. During normal periods of sleep, orexin system activity is suppressed, suggesting it is possible to purposefully facilitate the initiation and maintenance of sleep by interfering with orexin neurotransmission with lemborexant. Extensive in vitro and non-clinical testing of lemborexant supported the supposition that lemborexant has a low risk of QT prolongation at therapeutic and supratherapeutic exposures in humans. A Phase III study of lemborexant in insomnia is underway, and in addition, Eisai has announced the initiation of Phase II clinical studies of lemborexant in patients with irregular sleep-wake rhythm disorder.

Lorlatinib is an investigational medicine that inhibits the anaplastic lymphoma kinase (ALK) and ROS1 proto-oncogene. Lorlatinib was specifically designed to inhibit tumor mutations that drive resistance to other ALK inhibitors. Lorlatinib has in vitro activity against ALK and number of other tyrosine kinase receptor related targets including ROS1, TYK1, FER, FPS, TRKA, TRKB, TRKC, FAK, FAK2, and ACK. Lorlatinib demonstrated in vitro activity against multiple mutant forms of the ALK enzyme, including some mutations detected in tumors at the time of disease progression on crizotinib and other ALK inhibitors. Moreover, lorlatinib possesses the capability to cross the blood-brain barrier, allowing it to reach and treat progressive or worsening brain metastases as well. Lorlatinib is a third-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI) indicated for the treatment of patients with ALK-positive metastatic non-small cell lung cancer (NSCLC) whose disease has progressed on a) the prior use of crizotinib and at least one other ALK inhibitor for metastatic disease, or b) the prior use of alectinib as the first ALK inhibitor therapy for metastatic disease, or c) the prior use of certinib as the first ALK inhibitor therapy for metastatic disease.

Revefenacin (trade name Yupelri is a long-acting muscarinic antagonist developed by Mylan Ireland ltd for the treatment of chronic obstructive pulmonary disease (COPD). It has similar affinity to the subtypes of muscarinic receptors M1 to M5. In the airways, it exhibits pharmacological effects through inhibition of M3 receptor at the smooth muscle leading to bronchodilation. The competitive and reversible nature of antagonism was shown with human and animal origin receptors and isolated organ preparations. In preclinical in vitro as well as in vivo models, prevention of methacholine- and acetylcholine-induced bronchoconstrictive effects was dose-dependent and lasted longer than 24 hours.