FDA Approves Iyuzeh (latanoprost ophthalmic solution) for the Reduction of Elevated Intraocular Pressure (IOP) in Patients with Open-Angle Glaucoma or Ocular Hypertension

In continuation of my update on Latanoprost

Thea Pharma, Inc. (“Thea”), the U.S. subsidiary of Europe’s leading independent pharmaceutical company, Laboratoires Théa, dedicated to the research, development and commercialization of ophthalmic products,  announced U.S. Food and Drug Administration (FDA) approval of  the New Drug Application (NDA) of Iyuzeh™ (latanoprost ophthalmic solution) 0.005% for the reduction of elevated intraocular pressure (IOP) in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT).

Iyuzeh™ is the first and only clinically proven formulation of latanoprost available in the United States that is preservative-free. Iyuzeh™ is formulated without any of the preservatives commonly used in topical ocular preparations, including benzalkonium chloride (BAK). Iyuzeh™ has demonstrated consistent IOP-lowering effects and proven tolerability across multiple trials in the U.S. and Europe. In randomized, controlled clinical trials of patients with OAG or OHT with mean baseline IOP of 19-24 mmHg, Iyuzeh™ lowered IOP by 3 – 8 mmHg versus 4 – 8 mmHg by XALATAN® (latanoprost ophthalmic solution) 0.005%, which is preserved with BAK.

“The approval of Iyuzeh™ is a significant milestone for Théa Group, as this is our first FDA approval for a prescription ophthalmic medicine, for our U.S. subsidiary,” said Jean-Frédéric Chibret, President of the Théa Group. “Marketed outside of the U.S. as Monoprost®, the market leading prostaglandin analogue (PGA) in volume, is available in over 46 countries around the world, including France, Germany, Spain, United Kingdom, Italy, and Canada. We are extremely proud to bring our unique preservative-free latanoprost eye drop, Iyuzeh™ to the U.S.

“Our novel patent protected formulation has been made possible by Théa’s innovative scientists. They were able to solve the challenges of solubilizing and stabilizing latanoprost such that Iyuzeh does not need to be manufactured, distributed, or stored at refrigerated temperatures unlike some other competitive brand and generic latanoprost and PGA products. Additionally, Théa is responding to an important unmet need across all stakeholders in the treatment of OAG and OHT. Many patients on preserved glaucoma medications experience moderate to severe signs and symptoms of ocular surface disease (OSD) that can cause discomfort for patients, frustration for physicians, and drive additional costs for payers,” said Susan Benton, Thea’s U.S. President. “We look forward to introducing Iyuzeh™ to U.S. eyecare practitioners in the second half of 2023.”

About Iyuzeh™

Iyuzeh™ (latanoprost ophthalmic solution) 0.005%, an opalescent, white to slightly yellow ophthalmic solution, is a topical formulation of latanoprost that is indicated for the reduction of elevated intraocular pressure (IOP) in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT). Iyuzeh™ does not contain a preservative – it is the first and only preservative-free formulation of latanoprost, the most prescribed prostaglandin F2α analogue (PGA) in the United States. The recommended dosage of Iyuzeh™ is one drop in the affected eye(s) once daily in the evening. If one dose is missed, treatment should continue with the next dose as normal. Reduction of the IOP starts approximately 3 to 4 hours after administration and the maximum effect is reached after 8 to 12 hours. IOP reduction is present for at least 24 hours.

In the two clinical trials conducted with Iyuzeh™ (latanoprost ophthalmic solution) 0.005%, the most frequently reported ocular adverse reactions were conjunctival hyperemia (34%) and eye irritation (19%) compared to XALATAN, the preserved 0.005% latanoprost reference product which reported conjunctival hyperemia (37%) and eye irritation (31%).

https://en.wikipedia.org/wiki/Latanoprost

FDA Approves Rocklatan (netarsudil and latanoprost ophthalmic solution) for the Reduction of Intraocular Pressure in Open-Angle Glaucoma or Ocular Hypertension

In continuation of my update on latanoprost 

Aerie Pharmaceuticals, Inc. (NASDAQ:AERI) (Aerie or the Company), an ophthalmic pharmaceutical company focused on the discovery, development and commercialization of first-in-class therapies for the treatment of patients with open-angle glaucoma, retinal diseases and other diseases of the eye,   announced that the U.S. Food and Drug Administration (FDA) has approved Rocklatan (netarsudil and latanoprost ophthalmic solution) 0.02%/0.005% to reduce elevated intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension. 

Rocklatan is a once-daily eye drop that is a fixed-dose combination of latanoprost, the most widely-prescribed prostaglandin analog (PGA), and netarsudil, the active ingredient in Rhopressa (netarsudil ophthalmic solution) 0.02%, a first-in-class Rho kinase (ROCK) inhibitor specifically designed to target the trabecular meshwork (the eye’s principal drainage pathway). The diseased trabecular meshwork is considered to be the main cause of elevated IOP in open-angle glaucoma and ocular hypertension. Rhopressa® works by restoring outflow through the trabecular meshwork, while latanoprost increases fluid outflow through a secondary mechanism known as the uveoscleral pathway.

Aerie launched Rhopressa® in the United States in April 2018. The Company plans to launch Rocklatan™ in the United States in the second quarter of 2019.

“We are in the unique position of receiving FDA approval on a second glaucoma treatment less than a year from the U.S. launch of Rhopressa®,” said Vicente Anido, Jr., Ph.D., chairman and chief executive officer at Aerie. “Together, Rocklatan™ and Rhopressa® give us a broad therapeutic franchise, based on our ROCK inhibitor netarsudil, that addresses many of the needs of clinicians and patients in a wide variety of treatment settings. Our existing salesforce, which has been calling on U.S. eye-care professionals since last May, is very well positioned to introduce Rocklatan™ to these doctors and help them understand the clinical utility of both products in the care of their patients with glaucoma. We have also been working diligently on securing favorable reimbursement for our products, with Rhopressa® now enjoying broad commercial and Medicare Part D coverage, and Rocklatan™ already under review by major payers.”

The FDA approval of Rocklatan is based on data from two Phase 3 registration trials, MERCURY 1 and MERCURY 2. In these studies, Rocklatan™ achieved its primary 90-day efficacy endpoint as well as positive 12-month safety and efficacy results, demonstrating statistically superior IOP reduction over latanoprost and netarsudil at every measured time point. More than 60% of patients taking Rocklatan™ in the two MERCURY studies achieved an IOP reduction of 30% or more, a frequency that was nearly twice that achieved by participants taking latanoprost alone. Rocklatan™ also helped more patients get to low target pressures. Nearly twice as many patients taking Rocklatan™ reached 16 mmHg or lower and nearly three times as many reached 14 mmHg or lower compared to latanoprost.

In the two MERCURY studies, Rocklatan treatment was associated with generally mild and tolerable ocular adverse events, with minimal systemic side effects. The most common ocular adverse event in controlled clinical studies with Rocklatan™ was conjunctival hyperemia. Ninety percent of patients who experienced hyperemia reported it as mild and 5% discontinued because of it. Other common ocular adverse effects reported in the studies include instillation site pain, corneal verticillata and conjunctival hemorrhage.

About Rocklatan

Indications and Usage

Rocklatan (netarsudil and latanoprost ophthalmic solution) 0.02%/0.005% is indicated for the reduction of elevated intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension.

Select Important Safety Information

Although not observed in the two MERCURY studies, latanoprost has been reported to cause changes to pigmented tissues, including pigmentation of the iris, periorbital tissue (eyelid) and eyelashes. Iris pigmentation is likely to be permanent. Latanoprost has also been associated with gradual changes to eyelashes including increased length, thickness and number of lashes. These changes are usually reversible.

Ewf https://www.drugbank.ca/drugs/DB00654

https://www.biospace.com/article/fda-approves-aerie-pharma-s-glaucoma-combo-eye-drops/

FDA Approves Xelpros (latanoprost ophthalmic emulsion) to Treat Open-angle Glaucoma or Ocular Hypertension

In continuation of my update on latanoprost

Sun Pharmaceutical Industries Ltd. and Sun Pharma Advanced Research Company Ltd. (SPARC) announced U.S. Food and Drug Administration (USFDA) approval for the New Drug Application (NDA) of Xelpros (latanoprost ophthalmic emulsion) 0.005% for the reduction of elevated intraocular pressure (IOP, or pressure inside the eye) in patients with open-angle glaucoma or ocular hypertension. This approval is from Sun Pharma’s Halol (Gujarat, India) facility.

Sun Pharma in-licensed Xelpros from SPARC in June 2015 and this approval will trigger a milestone payment to SPARC. SPARC is also eligible for milestone payments and royalties on commercialization of Xelpros in the US.

Xelpros is the first and only form of latanoprost that is not formulated with benzalkonium chloride (BAK), a preservative commonly used in topical ocular preparations. Xelpros is developed using SPARC’s proprietary Swollen Micelle Microemulsion (SMM) technology.

“As the only BAK-free version of latanoprost, Xelpros will be an important and alternative treatment option for individuals with open-angle glaucoma or ocular hypertension,” said Abhay Gandhi, CEO, North America, Sun Pharma. “This approval, coming less than one month following the approval of CEQUA™ (cyclosporine ophthalmic solution) 0.09%, reaffirms the strength of Sun Pharma’s fast-growing Ophthalmics division and its commitment to serving the needs of patients with ocular disorders.”

Anil Raghavan, CEO, SPARC said, “Approval of Xelpros by USFDA is a significant milestone for SPARC. It is also a validation of our SMM technology which helps to solubilize drugs that have limited or no solubility thus eliminating the need for benzalkonium chloride (BAK).”

In randomized, controlled clinical trials of patients with open-angle glaucoma or ocular hypertension with a mean baseline Intraocular pressure (IOP) of 23-26 mmHg, Xelpros lowered IOP by a mean of up to 6-8 mmHg.

Xelpros will be commercialized in the U.S. by Sun Ophthalmics, the branded ophthalmic division of Sun Pharmaceutical Industries Ltd.’s wholly owned subsidiary.

FDA Approves Vyzulta (latanoprostene bunod) Ophthalmic Solution for Open-Angle Glaucoma, Ocular Hypertension

Valeant Pharmaceuticals International, Inc.'s   announced that the U.S. Food and Drug Administration (FDA) has approved the New Drug Application (NDA) for Vyzulta (latanoprostene bunod ophthalmic solution, 0.024%). Vyzulta, the first prostaglandin analog with one of its metabolites being nitric oxide (NO), is indicated for the reduction of intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension.¹

"With today's approval of Vyzulta, our customers and their patients with glaucoma now have a new treatment option that can help provide consistent and sustained IOP lowering, the only modifiable risk factor that can help slow down the progression of the disease," said Joseph C. Papa, chairman and CEO, Valeant. "We expect to make this new advancement available for those who suffer with glaucoma before the end of the year."

Following topical administration, Vyzulta, a once daily monotherapy with a dual mechanism of action, works by metabolizing into two moieties, latanoprost acid, which primarily works within the uveoscleral pathway to increase aqueous humor outflow, and butanediol mononitrate, which releases NO to increase outflow through the trabecular meshwork and Schlemm's canal. The most common ocular adverse events include conjunctival hyperemia, eye irritation, eye pain and instillation site pain. Increased pigmentation of the iris and periorbital tissue and growth of eyelashes can occur. In glaucoma patients, damage to the trabecular meshwork, through which the majority of the aqueous humor passes, can lead to reduced drainage and as a result elevated IOP. Lowering IOP, even in patients with normal baseline levels, can delay, or even prevent damage to optic nerves, helping to reduce the risk of glaucomatous visual field loss.

"Vyzulta represents the first FDA-approved therapy developed through our proprietary NO-donating research platform," said Michele Garufi, chairman and CEO of Nicox. "We look forward to continuing to leverage our platform in the development of additional innovative ophthalmic compounds."

Preclinical studies have shown that NO plays a role in controlling IOP in normal eyes by increasing aqueous humor outflow through the trabecular meshwork and Schlemm's canal. Studies have also demonstrated that patients with glaucoma have reduced levels of NO signaling in their eyes, providing a rationale for the therapeutic value of NO-releasing molecules for patients with open-angle glaucoma or ocular hypertension.

"The safety and efficacy of Vyzulta has been well-established through multiple clinical studies, which have demonstrated positive results, including statistically significant differences in IOP lowering compared to timolol and latanoprost," said Robert N. Weinreb, M.D., chairman and distinguished professor of Ophthalmology and director, Hamilton Glaucoma Center at the University of California San Diego. "As one molecule with a dual mechanism of action, Vyzulta provides a new treatment option that works to reduce IOP by increasing the outflow through both the trabecular meshwork and the uveoscleral pathways."

FDA Approves Omlonti (omidenepag isopropyl ophthalmic solution) for Reduction of Elevated Intraocular Pressure in Primary Open-Angle Glaucoma or Ocular Hypertension

Santen Inc., the U.S. subsidiary of Santen Pharmaceutical Co., Ltd. (Santen), and UBE Corporation (UBE)   announced   the U.S. Food and Drug Administration (FDA)   approval of Omlonti (omidenepag isopropyl ophthalmic solution) 0.002% eye drops for the reduction of elevated intraocular pressure (IOP) in patients with primary open-angle glaucoma or ocular hypertension. The approval date was September 22.

Omlonti is developed jointly by Santen and UBE. Omidenepag isopropyl, the active pharmaceutical ingredient in Omlonti, developed by UBE, is a relatively selective prostaglandin EP2 receptor agonist, which increases aqueous humor drainage through the conventional (or trabecular) and uveoscleral outflow pathways, and the only product with this pharmacological action. Omlonti was launched in Japan as Eybelis® ophthalmic solution 0.002% in November 2018, and was filed for marketing approval in Asian countries in stages. The product was released in five countries and regions beginning in February 2021.

“Glaucoma prevalence is increasing as the global population ages. Supporting patients by protecting vision across the continuum of clinical care in glaucoma is a significant aim for Santen to reduce the social and economic opportunity loss of people around the world caused by eye conditions,” explains Peter Sallstig, Chief Medical Officer of Santen. “This approval is an important milestone in our ambition to tackle unmet needs in eye health and advances our goal of realization of “Happiness with Vision”. It also represents our first glaucoma offering in the U.S. We are pleased to provide doctors and patients in the U.S. with a new option to help control IOP for the more than three million Americans affected by glaucoma1 or ocular hypertension.”

“UBE Corporation is committed to working on new drug discoveries on a daily basis with the aim of providing patients with more treatment options for diseases with high unmet needs," said Yoichi Funayama, Senior Executive Officer and General Manager of the Pharmaceutical Division, UBE Corporation. “We are very pleased that this ophthalmic solution has been approved for glaucoma in the U.S., following approvals in Japan and Asia. We have high expectations that omidenepag isopropyl will provide a new treatment option for more patients suffering from glaucoma and ocular hypertension through Santen.”

Omlonti was evaluated in three randomized and controlled clinical trials in subjects with open-angle glaucoma or ocular hypertension with average baseline IOP of 24-26 mm Hg. The double-masked treatment duration was three months in all three studies. The third study included a 9-month open-label treatment period following the 3-month double-masked treatment period. In the three studies, IOP reductions were observed for all treatment arms. In the Omlonti arm, the reduction in IOP ranged from 5-7 mm Hg across all three studies. The corresponding reductions for the timolol and latanoprost arms were 5-7 mm Hg and 6-8 mm Hg, respectively.

Glaucoma causes damage to the optic nerve resulting in visual field loss, and remains a leading cause of irreversible blindness worldwide.2 Since the disease is generally progressive, early detection and treatment to control the progression are crucial, and lowering IOP is the most effective means of avoiding damage to the optic nerve. The estimated number of patients globally in 2020 was 76 million, and it is expected to increase to 95 million by 2030.3 Primary open-angle glaucoma is the most common type of glaucoma. Ocular hypertension, which affects millions, can lead to glaucoma and vision loss if untreated.4

“Treatments that focus on IOP reduction help to slow or prevent further loss of vision for those with glaucoma or ocular hypertension. However, not all patients respond to the same treatments, and some may not have successful outcomes,” said Jason Bacharach, MD, Medical and Research Director at North Bay Eye Associates, Inc. “The approval of omidenepag isopropyl ophthalmic solution 0.002% provides doctors with another safe and effective option to use when treating patients with these sight-threatening conditions.”

 https://en.wikipedia.org/wiki/Omidenepag