PTGFR

The eyedrop is an option for those who are benefitting from preservative-free eye drops. Credit: Andrey Sayfutdinov/Shutterstock. China’s National Medical Products Administration (NMPA) has approved the marketing authorisation application of Santen Pharmaceutical’s Tapcom to treat individuals with open-angle glaucoma or ocular hypertension. This fixed-combination eye drop comprising tafluprost 0.0015% and timolol 0.5% is designed to lower intraocular pressure (IOP) for individuals with this condition. Glaucoma damages the optic nerve and results in visual field loss. The eye drop offers a therapeutic alternative for individuals whose topical beta-blockers or prostaglandin derivatives monotherapies have not achieved target IOP. It is also an option for those who are benefitting from preservative-free eye drops in prolonged topical usage of glaucoma medication. Tapcom is the country’s first preservative-free ophthalmic combo formulation to include a first-line prostaglandin derivative. Its two active ingredients, tafluprost and timolol maleate, work through different mechanisms to reduce IOP. Tafluprost acid, the active metabolite of tafluprost, is a prostanoid FP receptor agonist that promotes aqueous humour outflow. A nonselective β-receptor inhibitor, timolol maleate, decreases the production of aqueous humour. Tapcom has gained approval in 40 countries and regions, including Asia and Europe. Santen Pharmaceutical chief medical officer Peter Sallstig stated: “Glaucoma remains the leading cause of irreversible blindness worldwide, deeply impacting the quality of life of many patients. “Therefore, Santen has prioritised glaucoma as a key therapeutic focus, dedicating ourselves to the development of treatments that meet patients’ needs and the delivery of high-quality ophthalmic drugs. The approval of Tapcom in China represents a significant milestone, offering new treatment options for Chinese glaucoma patients and advancing the field of glaucoma care.” In November 2024, the company and Arctic Vision signed a commercial partnership agreement for the ARVN001 suprachoroidal injectable suspension for uveitic macular oedema and other ocular conditions.

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: TirzepatideTarget: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. 👇Please click on the image below to directly access the latest data (R&D Status | Core Patent | Clinical Trial | Approval status in Global countries) of this drug. 2.ChemoCentryx: AvacopanTarget: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:RYALTRISTarget: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:ErenumabTarget: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:EvocalcetTarget: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: BrexpiprazoleTarget: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: TapcomTarget: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.

PDUFA Date Set for December 22, 2023 ALISO VIEJO, Calif.--(BUSINESS WIRE)-- Glaukos Corporation (NYSE: GKOS), an ophthalmic medical technology and pharmaceutical company focused on novel therapies for the treatment of glaucoma, corneal disorders and retinal diseases, today announced it has received the “Day 74” notification from the U.S. Food and Drug Administration (FDA) acknowledging the previously submitted New Drug Application (NDA) for iDose® TR (travoprost intraocular implant) is sufficiently complete to permit a substantive review. The Prescription Drug User Fee Act (PDUFA) goal date for the completion of the FDA’s review of the iDose TR NDA is set for December 22, 2023. This date reflects a standard 10-month review period and is consistent with management’s expectations for the 505(b)(2) filing. “The acceptance of the iDose TR NDA represents another important step in bringing this potential game-changing therapy one step closer to patients who may need a new treatment alternative,” said Thomas Burns, Glaukos chairman and chief executive officer. “We look forward to working closely with the FDA throughout their review process and continue to believe iDose TR can be a transformative novel technology able to fundamentally improve the treatment paradigm for patients with open-angle glaucoma or ocular hypertension.” The NDA submission includes data from two Phase 3 pivotal trials of iDose TR, which both successfully achieved the pre-specified primary efficacy endpoints through 3 months and demonstrated a favorable tolerability and safety pro 12 months. In addition, the submission also includes data from the iDose TR exchange trial, which included a second administration of iDose TR and removal of the original iDose TR , with the second iDose TR administration demonstrating a favorable safety pro a 12-month evaluation period. iDose TR is a micro-invasive intraocular implant designed to lower intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension. iDose TR is designed to continuously deliver therapeutic levels of a proprietary formulation of travoprost from within the eye for extended periods of time. It is designed such that it can be removed and replaced with a new iDose TR, thus potentially offering a long-term dropless alternative to daily eye drop treatment. iDose TR is intended to address ubiquitous patient non-compliance and chronic side effects associated with topical IOP-lowering medications. About Glaukos Glaukos ( ) is an ophthalmic medical technology and pharmaceutical company focused on developing and commercializing novel therapies for the treatment of glaucoma, corneal disorders and retinal diseases. Glaukos first developed Micro-Invasive Glaucoma Surgery (MIGS) as an alternative to the traditional glaucoma treatment paradigm, launching its first MIGS device commercially in 2012, and continues to develop a portfolio of technologically distinct and leverageable platforms to support ongoing pharmaceutical and medical device innovations. Products or product candidates for each of these platforms are designed to advance the standard of care through better treatment options across the areas of glaucoma, corneal disorders and retinal diseases. Forward-Looking Statements All statements other than statements of historical facts included in this press release that address activities, events or developments that we expect, believe or anticipate will or may occur in the future are forward-looking statements. Although we believe that we have a reasonable basis for forward-looking statements contained herein, we caution you that they are based on current expectations about future events affecting us and are subject to risks, uncertainties and factors relating to our operations and business environment, all of which are difficult to predict and many of which are beyond our control, that may cause our actual results to differ materially from those expressed or implied by forward-looking statements in this press release. These potential risks and uncertainties include, without limitation, the timing and extent to which we obtain regulatory approval for investigational products such as iDose TR, our ability to successfully commercialize such products, the ability to obtain and maintain adequate financial coverage and reimbursement for this product, and the continued efficacy and safety pro this product as reported in the pivotal trials and other clinical studies. These and other risks, uncertainties and factors related to Glaukos, and our business are described in detail under the caption “Risk Factors” and elsewhere in our Quarterly Report on Form 10-Q for the quarter ended March 31, 2023, which was filed with the Securities and Exchange Commission (SEC) on May 4, 2023. Our filings with the SEC are available in the Investor Section of our website at or at . In addition, information about the risks and benefits of our products is available on our website at . All forward-looking statements included in this press release are expressly qualified in their entirety by the foregoing cautionary statements. You are cautioned not to place undue reliance on the forward-looking statements in this press release, which speak only as of the date hereof. We do not undertake any obligation to update, amend or clarify these forward-looking statements whether as a result of new information, future events or otherwise, except as may be required under applicable securities law.