Mometasone Furoate

This article will review currently applied listed GPCR-targeting drugs, and the associated popular GPCR class targets and drug development opportunities worth paying attention to. 1.Eli Lilly: Tirzepatide Target:GIPR + GLP-1R Tirzepatide is a novel GIPR and GLP-1R dual agonist developed by Eli Lilly. In preclinical and clinical trials, compared to selective GLP-1 receptor agonists, GIP/GLP-1 dual agonists have been shown to better control blood sugar and reduce weight. Therefore, it is receiving increasing attention as a new therapeutic drug for controlling blood sugar and weight. In 2022, Tirzepatide was approved for the first time in the United States for the treatment of adult type II diabetes as an adjunct to diet and exercise. Subsequently, Tirzepatide was approved in the European Union and Japan for the treatment of type II diabetes. 2.ChemoCentryx: Avacopan Target:C5aR Avacopan(Tavneos) is an orally administered, first-in-class selective complement 5a receptor (C5aR) antagonist, discovered and developed by ChemoCentryx. This drug is used as an adjunctive therapy for ANCA-associated vasculitis in adult patients. Anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) is a rare ("oligo-immune") systemic small-vessel vasculitis, with an estimated incidence of 3 per 100,000 annually, characterized by the presence of ANCAs in the serum. The entire course of AAV includes granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), eosinophilic granulomatosis with polyangiitis (EGPA), and drug-induced AAV. Despite its complex pathophysiology, research over the past approx. 20 years has determined the crucial role of the alternative complement pathway, particularly the interaction of C5a with the C5aR receptor in AAV. Avacopan was first approved for marketing in Japan on September 27, 2021, and was subsequently approved in the United States, European Union, Canada, and Australia for the treatment of adult patients with ANCA-associated vasculitis, granulomatosis with polyangiitis, and microscopic polyangiitis. In addition, research is ongoing for other potential clinical indications, such as hidradenitis suppurativa and C3 glomerulopathy. 3.Pfizer: Rimegepant Sulfate Target:CGRP Receptor Rimegepant is an orally administered CGRP receptor antagonist used for the acute treatment of migraine in adults, with or without aura. Initially developed by the BMS(BMS-742413), the newly established biotech company Biohaven Pharmaceutical acquired the exclusive global development and commercialization rights to Rimegepant in 2016. The Biohaven team conducted a series of clinical studies and analyses around Rimegepant and developed the derivative migraine nasal spray drug, Zavegepant. In May 2022, Pfizer announced that it would acquire Biohaven for a total cash consideration of approximately 11.6 billion USD. Rimegepant was first approved for marketing in the United States on February 27, 2020, and subsequently received approval in Israel, the United Arab Emirates, Kuwait, the European Union, and Iceland, among others. Currently, the drug is being tested in clinical trials for conditions like chronic sinusitis, nasal polyps, and trigeminal neuralgia. 4. Glenmark:RYALTRIS Target:H1R+GR RYALTRIS is a new compound prescription nasal spray developed by the Indian pharmaceutical company, Glenmark. This medication has the dual efficacy of activating glucocorticoid receptor (GR) and antagonizing histamine H1 receptor (H1R). Mometasone is a moderately potent synthetic corticosteroid that acts as a glucocorticoid receptor agonist, possessing anti-inflammatory, anti-itch, and vasoconstrictive properties. Olopatadine, on the other hand, is an antagonist of histamine H1 receptors used for the treatment of allergic conjunctivitis and rhinitis. Since histamine is the primary inflammatory mediator causing inflammation and allergic reactions, Olopatadine works by blocking the action of histamine receptors. Compared to other anti-allergic ophthalmic drugs, Olopatadine does not interfere with the cell membrane, thus offering good comfort and tolerability. RYALTRIS was first approved for marketing in Australia in 2019, and subsequently received approval for listing in South Africa, the UK, the US, Canada, and other countries. In 2019, Grand Pharmaceutical and Glenmark signed an exclusive licensing agreement, in which Glenmark granted Grand Pharmaceutical the exclusive rights to sell RYALTRIS in China. Glenmark would be responsible for the manufacture and supply of the authorized product, while Grand Pharmaceutical would be in charge of the clinical trials and registration work for the authorized product in China and can exclusively sell the approved product in China for 20 years upon approval. 5. Amgen:Erenumab Target:CGRP Erenumab is a human monoclonal antibody developed by Amgen and is the first monoclonal antibody drug targeting GPCR approved by the FDA. Erenumab can specifically bind to and antagonize the Calcitonin Gene-Related Peptide Receptor (CGRPR), thus preventing migraines. In April 2017, Amgen announced an expanded commercial collaboration with Novartis on Erenumab, which is being studied for the prevention of migraine. This expanded business cooperation is based on the global neuroscience collaboration established by Novartis and Amgen in 2015 in the areas of Alzheimer's disease and migraine. Novartis initiated two clinical trials in China in 2019 to evaluate the safety and efficacy of Erenumab injection in the treatment of migraines. Erenumab was first approved for marketing in the United States in 2018, and was subsequently approved in Australia, Iceland, Norway, Switzerland, Canada, and Japan. In addition to the treatment of migraines, clinical trial research is ongoing for other indications, including headaches, hot flashes, temporomandibular joint dysfunction syndrome, stable angina. 6. Kyowa Kirin:Evocalcet Target:CaSR Evocalcet is a Calcium-Sensing Receptor (CaSR) agonist developed by Kyowa Kirin, used for the treatment of hypercalcemia, secondary hyperparathyroidism, and other related conditions. Kyowa Kirin has applied for two clinical trials in China to evaluate the effectiveness of Evocalcet in treating secondary hyperparathyroidism in patients undergoing maintenance dialysis for chronic kidney disease. As of now, Evocalcet has only been approved for marketing in Japan. 7. Otsuka Pharmaceutical: Brexpiprazole Target:5-HT1A+5-HT2A+D2R Brexpiprazole is a serotonin-dopamine activity modulator developed by Otsuka Pharmaceutical, used as an adjunctive treatment for severe depression, schizophrenia, and agitation associated with dementia caused by Alzheimer's disease. Brexpiprazole is an atypical antipsychotic and a novel D2 dopamine and serotonin 1A partial agonist, known as a serotonin-dopamine activity modulator. It has a high affinity for serotonin, dopamine, and alpha-adrenergic receptors. Structurally, Brexpiprazole is very similar to another atypical antipsychotic drug, Aripiprazole, but Brexpiprazole has a different affinity for binding with dopamine and serotonin receptors. Compared to Aripiprazole, Brexpiprazole is less likely to produce adverse reactions mediated by partial agonist, such as extrapyramidal symptoms, due to its lower intrinsic activity at the D2 receptor. Brexpiprazole was first approved in the United States in 2015, and subsequently approved in Canada, Japan, and the European Union. In addition to treating depression, this drug is undergoing global clinical trials and research for multiple indications including agitation, schizophrenia, Alzheimer's disease, and performance anxiety. 8. Santen: Tapcom Target:PTGFR+βAR Tapcom is a combination eye drop medication containing Tafluprost and Timolol Maleate, developed by Santen. Tafluprost is a prostaglandin analogue used in ophthalmology to reduce intraocular pressure in patients with ocular hypertension or open-angle glaucoma. Chemically, Tafluprost is a fluorinated analogue of prostaglandin F2-α. Timolol is a non-selective beta-adrenergic antagonist, used for the treatment of elevated intraocular pressure in patients with ocular hypertension or open-angle glaucoma. Tapcom was first approved for marketing in Japan in 2013, and subsequently received approval in countries including Iceland, France, Poland, and Germany. 9. Takeda:TeduglutideTarget:GLP-2R Teduglutide is a glucagon-like peptide-2 (GLP-2) analog developed by the British rare disease pharmaceutical giant, Shire Development, for the treatment of patients with short bowel syndrome (SBS) who require parenteral nutrition support. Teduglutide is comprised of 33 amino acids, and is manufactured using strains of E. coli that have been modified through DNA recombinant technology. Teduglutide differs from GLP-2 by one amino acid (alanine is replaced with glycine). This substitution results in Teduglutide having a longer duration of action than endogenous GLP-2 and a higher resistance to hydrolysis by the enzyme dipeptidyl peptidase-4. Teduglutide first received regulatory approval within the European Union in 2012, followed by approval in the United States and Japan, in all cases for the treatment of SBS. In 2019, Takeda Pharmaceuticals spent an astounding £46 billion to acquire Shire Development, in a move that has been dubbed as a "snake swallowing an elephant" merger in the pharmaceutical world. This acquisition propelled Takeda Pharmaceuticals into the list of top 10 global biopharmaceutical companies. Clinical research on the application of Teduglutide for the treatment of Crohn's Disease and kidney disorders was discontinued due to this acquisition. 10. AstraZeneca: Duaklir GenuairTarget:M3R+β2AR Duaklir Genuair is a combined Aclidinium Bromide/Formoterol Fumarate inhalation powder developed by AstraZeneca. This medication is used as a maintenance bronchodilator to alleviate the symptoms of disease in adults with chronic obstructive pulmonary disease (COPD). Among them, Aclidinium bromide is a novel long-acting muscarinic antagonist, and Formoterol fumarate is a long-acting β2 receptor agonist. Duaklir Genuair is administered by the Genuair dry powder inhaler twice a day and is the first combined medication that has shown a statistically significant improvement over monotherapy in terms of shortness of breath. Duaklir Genuair was first approved in the European Union in 2012, and subsequently in the United States in 2019, for the treatment of chronic obstructive pulmonary disease. The content above comes from the network. if any infringement, please contact us to modify.

Detailed results of the ACESO Phase II study published in the peer-reviewed medical journal Alimentary Pharmacology & TherapeuticsESO-101 leverages EsoCap’s unique drug delivery technology to achieve localized treatment of the esophageal lining with the anti-inflammatory corticosteroid mometasone furoate BASEL, Switzerland, Dec. 17, 2024 (GLOBE NEWSWIRE) -- EsoCap AG, the Swiss biotech company dedicated to improving the lives of patients with serious diseases of the upper gastrointestinal tract, announced today that the complete results of the ACESO Phase II study evaluating ESO-101 for the treatment of eosinophilic esophagitis have been published in Alimentary Pharmacology & Therapeutics1. The data demonstrate that ESO-101 was safe and well tolerated and improved both histologic and endoscopic outcomes in adults with active eosinophilic esophagitis (EoE). EoE is a chronic, local, immune-mediated esophageal disease characterized clinically by symptoms associated with esophageal dysfunction, including dysphagia (i.e., swallowing difficulties), food impaction, heartburn and vomiting, and histologically by eosinophil-dominated inflammation. The ACESO study was a randomized, placebo-controlled, double-blind Phase II study to evaluate the safety, tolerability, and efficacy of ESO-101 in adult patients with active EoE. ESO-101, EsoCap's lead product candidate, consists of a capsule with a rolled-up, thin mucoadhesive film with the anti-inflammatory corticosteroid mometasone furoate. The study was conducted at 14 medical centers in five European countries and enrolled 43 participants with EoE and a peak eosinophil count of ≥15 eosinophils per high-power field (hpf). Patients were randomized in a 2:1 ratio and treated with ESO-101 or placebo once daily for 28 days. The ACESO trial met its primary endpoint with a statistically significant reduction of the peak eosinophil count from baseline in histology samples. In the ESO-101 group, the mean reduction was 49.1 ± 88.4 eosinophils/hpf (p=0.0318). In addition, while none of the patients from the placebo group achieved histological remission, 48% and 44% of patients achieved <15 and <6 eosinophils/hpf, respectively, when treated with ESO-101 (p=0.0028 and p=0.0035, respectively). Patients treated with ESO-101 had a significant response in the eosinophilic esophagitis endoscopic reference score (EREFS) scores, indicating promising potential for remodeling effects despite the short treatment duration. A significant improvement of dysphagia symptoms was observed after a 4-week period with a high placebo response: a benefit of ESO-101 in relieving EoE dysphagia and odynophagia symptoms is expected to be seen in future clinical trials with a longer treatment period. Importantly, ESO-101 also demonstrated a highly favorable safety and tolerability profile with a notable absence of oral and oropharyngeal as well as esophageal candidiasis, which is commonly observed with topical corticosteroid treatment. Compliance was high, with 100% in the ESO-101 and 93% in the placebo groups. The high level of patient satisfaction with the handling of the study medication underlines the user-friendliness of the ESO-101 drug-delivery system. “The detailed results of the ACESO trial provide robust evidence for the efficacy and safety of ESO-101, a novel drug delivery device for the long-lasting, targeted delivery of the anti-inflammatory corticosteroid mometasone furoate directly to the esophageal mucosa,” said Dr. Alfredo J. Lucendo, Department of Gastroenterology, Hospital General de Tomelloso, Spain, and coordinating principal investigator of the ACESO trial. “The trial’s rigorous design demonstrated significant improvements in inflammatory, histological, and endoscopic parameters compared to placebo, which underscores the potential of this treatment approach. For patients with eosinophilic esophagitis, this approach offers the potential for more effective disease management in a field where treatment options are scarce.” “At EsoCap, we are committed to transforming the lives of patients affected by esophageal diseases. The positive outcome of the ACESO Phase II study with ESO-101 and the publication in a peer-reviewed journal are an important validation of our targeted, topical delivery platform, which has been designed to increase mucosal contact time and drug deposition in the esophagus,” said Isabelle Racamier, CEO of EsoCap. “This marks an important milestone for EsoCap in advancing treatment options for eosinophilic esophagitis.” About eosinophilic esophagitis Eosinophilic esophagitis (EoE) is an increasingly recognized, chronic, local immune-mediated esophageal disease, characterized clinically by symptoms related to esophageal dysfunction and histologically by eosinophil-predominant inflammation. The symptoms of EoE include swallowing disorders, food impaction, vomiting, and heartburn. EoE is the leading cause of dysphagia and food impaction in children and young adults. The only treatment options for the condition are extremely strict diets, off-label treatment with steroids or proton pump inhibitors, an orodispersible budesonide tablet available only in limited territories, or an oral suspension of budesonide approved exclusively in the USA for a short treatment duration. These treatment options remain suboptimal for the vast majority of affected patients. A monoclonal antibody targeting Th2 cell-released cytokines such as interleukin-4 (IL-4) and interleukin-13 (IL-13) was approved to treat EoE globally for steroid resistant patients. Currently, about 500,000 patients worldwide suffer from this disease. The prevalence of EoE is over 6 in 10,000. The current incidence is estimated to exceed 5 cases per 100,000. The incidence of EoE increases with age and peaks at 30-50 years of age. About the ACESO Phase II trial The ACESO trial was a multicenter, randomized, double-blinded, placebo-controlled clinical Phase II trial evaluating the efficacy, tolerability, and safety of ESO-101 in adult patients with active EoE. Patients were treated once daily for 28 days. The trial’s primary objective was to evaluate efficacy based on histological response. Secondary objectives included efficacy based on 1) histological response and clinical symptoms, 2) clinical response assessed by patient-reported outcomes, and 3) endoscopic response; patient-reported treatment satisfaction; as well as evaluation of tolerability and safety. About ESO-101 The EsoCap system is a unique drug delivery system for the upper gastrointestinal tract, consisting of a capsule holder containing a hard gelatin capsule, with a rolled, thin mucoadhesive film, a sinker, and a soluble retainer. The capsule holder is screwed onto the lid of a drinking cup to facilitate swallowing while drinking from the cup. Upon swallowing, the film unrolls and sticks to the esophageal mucosa, where it dissolves, with a contact time of 15 minutes2,3, significantly longer than the mucosal contact time of pharmaceutical dosage forms, such as orodispersible tablets (less than one minute)4. The use of mometasone furoate as a swallowed aerosol formulation has been studied previously in several trials assessing its effect on EoE in adults. In these trials, mometasone furoate was shown to significantly decrease esophageal eosinophilic inflammation and improve clinical symptoms. ESO-101 was designed as a locoregional, esophagus-adjusted drug formulation and novel delivery system to optimize mucosal contact time and maximize esophageal deposition of mometasone furoate. ESO-101 has the potential to provide significant clinical benefits to EoE patients. About EsoCap EsoCap AG is a privately funded company based in Basel, Switzerland. EsoCap’s vision is to improve the lives of patients with serious diseases of the upper gastrointestinal tract through development of a unique and innovative topical drug delivery platform. Effective topical treatment of the esophagus is extremely difficult to achieve with the current standard of care, due to the ultra-short drug contact time of 45 seconds from the mouth to the stomach. Lead candidate ESO-101 has received Orphan Drug Designation from the U.S. Food & Drug Administration (FDA) for the treatment of EoE and is in clinical development for this indication. EsoCap has developed a unique, proprietary drug delivery platform enabling the efficient topical application of drug substances for the local treatment of diseases of the upper gastrointestinal tract. EsoCap has a strong and broad intellectual property position. For more information, please visit www.esocapbiotech.com and follow EsoCap on LinkedIn. Contacts: Isabelle Racamier, CEO EsoCap AG Malzgasse 9 4052 Basel, Switzerland isabelle.racamier@esocapbiotech.com Media Inquiries:MC Services AGDr. Regina Lutz, Dr. Johanna KoblerPhone: +49 89 210288-0esocap@mc-services.eu ____________________________ 1 Lucendo AJ, el al. Clinical trial: Safety and efficacy of a novel oesophageal delivery system for topical corticosteroids versus placebo in the treatment of eosinophilic oesophagitis. Aliment Pharmacol Ther 2025; https://doi-org.libproxy1.nus.edu.sg/10.1111/apt.18443 2 C Rosenbaum et al, 2021. Functionality and Acceptance of the EsoCap System—A Novel Film-Based Drug Delivery Technology: Results of an In Vivo Study. Pharmaceutics, 13 (6): 828.3 Krause et al., 2020. The EsoCap-system – An innovative platform to drug targeting in the esophagus. Journal of controlled release, 327:1–7.4 Burton et al., 1995. Intragastric Distribution of Ion-exchange Resins: a Drug Delivery System for the Topical Treatment of the Gastric Mucosa. J. of Pharmacy and Pharmacology, 47: 901-906.