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New drugs, delivery methods in the pipeline for ocular surface, retina, glaucoma
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NEW ORLEANS – A multitude of treatments options in development for the ocular surface, retina and glaucoma have the potential to greatly improve patient outcomes and quality of life, Chris Wroten, OD, DiplABO, said here at SECO.
Application technology
Eyenovia is developing a new Microdrop drug delivery device that a patient holds in front of their eye, lines up and pushes a button to release a 7-µL “spray.” This volume matches the average capacity of the fornix, he said, reducing wasted medication, unlike most droppers, which release 30 µL to 50 µL per drop.
“Not only is it a smaller drop, it’s more accurately delivered, and it’s electrically charged when it’s manufactured, which causes it to adhere to the epithelium, increasing contact time and reducing dosage frequency,” Wroten said.
The technology could deliver therapeutics for treating diseases such as glaucoma, dry eye and allergy, Eyenovia said on its website.
Ocular surface
“In ocular surface disease, we are seeing more and more opportunities to make a difference,” Wroten continued.
Oyster Point Pharma has two candidates for dry eye expected to move to phase 3 trials this year, OC-01 and OC-02, both of which are administered as nasal sprays.
“Who would have thought that we’d be doing dry eye therapy through the nose just a few years ago?” Wroten asked.
He also discussed regenerative medicine in eye care, specifically amniotic membranes.
“It’s still just relatively recent that we’ve embraced these and their opportunities to enhance care,” he said.
He noted that Bio-Tissue is expected to bring the amniotic membrane eye drop, Regenesol, to market in 2019.
“For the first time we might be able to avoid putting something on the eye other than a drop and get the same benefit as we have with the amniotic membranes,” Wroten said.
A company in Italy is developing similar technology, and other companies are using amniotic extract eye drops, he said.
Cequa (cyclosporine ophthalmic solution 0.09%), a treatment for dry eye, was approved by the FDA in August. Sun Pharmaceuticals nanomanufactured the drug into a unique molecule, a micelle that greatly enhances its efficacy, Wroten said.
“It forms a sphere when it’s in solution. Not only does it become round, but it has hydrophilic and hydrophobic properties, which can significantly increase efficacy,” he said.
“Could you imagine using cyclosporine to treat an inflammatory condition as severe as scleritis? Yet it’s being studied to potentially do just that,” Wroten added.
Retina
Optina (ultra-low dose danazol, Ampio Pharmaceuticals) is an oral medication in development for treating macular edema caused by diabetes and other etiologies. Large, late-stage U.S. clinical trials are currently underway.
“It’s very exciting to think about what implications this could have in eye care,” Wroten said.
A potent anti-VEGF medication, PAN 9086 (PanOptica), is an eye drop designed to halt neovascularization in the retina. It has successfully completed phase 1/2 trials and was effective in 50% of treated individuals. In comparison, current anti-VEGF medications are successful less than 50% of the time, he added.
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Glaucoma
Aerie Pharmaceuticals is developing Rocklatan (netarsudil/latanoprost ophthalmic solution), which pairs their Rho kinase (ROCK) inhibitor Rhopressa with a prostaglandin analog, collectively yielding a quadruple mechanism of action via enhanced episcleral venous outflow, relaxation of the trabecular meshwork, aqueous production suppression and increased uveoscleral outflow, Wroten said.
It is expected to be FDA approved in 2019, he said.
“We are seeing a lot of trial work with ROCK inhibitors,” Wroten said. “It’s easy to miss that ROCK inhibitors are a hot topic outside of glaucoma, too; they are being investigated for treatment of Fuch’s dystrophy and in neuromedicine as potential therapies for Alzheimer’s, Parkinson’s and amyotrophic lateral sclerosis (aka Lou Gehrig’s disease).”
“It shouldn’t be long until we have the very first sustained-release drug for glaucoma,” Wroten added. Sustained-release bimatoprost from Allergan is planned for market in the first quarter of 2020, he said.
All initial studies were done with intraocular administration into the anterior chamber of the eye, with efficacy lasting about 6 months, he said.
Companies are also exploring subconjunctival injection of sustained-release prostaglandins, which would be less invasive and avoid insult to the cornea, Wroten said.
An ocular ring of bimatoprost, which sits underneath the upper and lower eyelids, is also showing significant reduction in IOP for 6 months at a time, he said. The ring stayed in place in nine out of 10 patients for 6 months. Of those for whom it stayed in place, all but one said they could not tell it was there.
Alcon’s sustained-release travoprost, also in development, is a nanosized particle that sits in the anterior chamber and lowers IOP for an extended period (a 30% IOP reduction was sustained for 6 months after a single administration, he said).
Alcon is reportedly investigating subconjunctival injections of travoprost, as well.
Graybug Vision is a new company developing drugs to treat glaucoma, as well as wet AMD and diabetic retinopathy, he said.
“In glaucoma, everything they are developing is administered via subconjunctival injection,” he said. The company reports a library of more than 100 new molecular entities for glaucoma based upon prodrugs of currently approved molecules, ROCK inhibitors and other novel ocular hypotensive medications.
“We may see more and more movement in the future with injectable medications for glaucoma,” Wroten added.
He also talked about research from John Berdahl, MD, at Vance Thompson Vision, who worked with NASA to determine why astronauts returning from space were developing papilledema.
“Clearly if you’re in the vacuum of space, the anterior chamber of the eye, and thus the intraocular pressure, is going to be impacted by that environment much more than the intracranial pressure behind the lamina cribrosa will be,” Wroten said.
Berdahl proposed that the vacuum of space causes a significant drop in IOP, while intracranial pressure is less affected, creating a pressure gradient in which intracranial pressure far exceeds the IOP.
As a result, the optic nerve is pushed forward, resulting in papilledema, Wroten said.
Berdahl applied this theory to low tension glaucoma, as well, suggesting that a large pressure gradient in the other direction could inhibit axonal transport and metabolism, leading to apoptosis. His research has confirmed that in many cases of low tension glaucoma, a large difference in the post-lamina cribrosa intracranial pressure and the pre-lamina cribrosa IOP does exist.
This led to Berdahl’s development of Balance Goggles, which a patient would wear at night to equalize that pressure gradient.
“We’ll see if it receives FDA approval and makes it to market,” Wroten said, noting that if approved, it would be the first nonpharmacological, nonsurgical treatment for glaucoma of any kind. – by Abigail Sutton
Reference:
Wroten, C. See the vision of tomorrow forum. Presented at: SECO; February 22, 2019; New Orleans.
Disclosure: Wroten reported no relevant financial disclosures.