OIS Glaucoma Showcase Take-Home: Glaucoma Market Poised For Growth

A growing number of people living past age 60 years, innovation to increase the effectiveness or accessibility of care, and competition are the largest factors driving today’s glaucoma market, said Peter Downs, a writer and analyst with Market Scope at the OIS Glaucoma Innovation Showcase, held virtually. Link to video

As for companies driving innovation in glaucoma, eight of them presented their potentially disruptive advancements, ranging from goggles to stimulate the optic nerve—damage to which is the classic pathophysiology of glaucoma—to drugs and technologies that aim to reduce intraocular pressure (IOP)—thought to be the key mechanism that cause optic nerve damage.

Pharmaceutical Outlook

On the pharmaceutical side, few competitors exist, with Novartis, Allergan/AbbVie, and Santen Pharmaceutical reaping almost 60% of revenues, Downs said. Fixed-combination agents and prostaglandins account for two-thirds of all revenues. On the surgical side, there are many more competitors and less concentration, he said. Glaukos, the largest company, has less than a third of the market. Tube shunts and canalicular surgery devices are the fastest-growing products.

Generic prostaglandins and beta blockers are growing in almost every market. Emerging options, such as Rho kinase (ROCK) inhibitors, which Aerie Pharmaceuticals have brought to market, and nitric oxide–donating compounds are gaining in popularity. Minimally invasive glaucoma surgery (MIGS) devices continue to grow in popularity. Primary selective laser trabeculoplasty (SLT) is increasing.

Market Potential

Revenues for glaucoma pharmaceuticals are predicted to increase from $1.9 billion to $2.7 billion from 2021 through 2026, said Downs, with sustained delivery devices being the fastest growth category. Surgical devices are projected to grow from $430.7 million this year to $950.2 million in 2026, with MIGS surgery and canalicular surgery the fastest-growing categories.

Technologies that could disrupt the glaucoma market include low-cost, automated SLT; cost-effective sustained-release drug platforms; neuroprotectives or other agents that prevent glaucoma progression; and the advent of a gene therapy, Downs said.

The following eight companies presented updates on their development programs.

Neuromodtronic is advancing its Eyetronic goggles device, which emits gentle electrical pulses to stimulate the optic nerve to prevent further damage and restore lost vision. The device, which received European certification in 2016, has been used to treat 1,200 eyes in 6,000 individual sessions without any serious adverse events, said Karl Schweitzer, CEO and cofounder. He reported that a 12-month postmarket trial of 101 eyes in Germany found a halt in disease progression in 63% of eyes and improved visual field outcomes in 60%. He said the company is raising $20 million for an international randomized controlled trial to access the US market. In parallel, the company is evaluating the device in retinitis pigmentosa, age-related macular degeneration and diabetic retinopathy, and supporting investigator-initiated trials in conditions such as multiple sclerosis. Investigators also are developing a similar device for in-home use. Link to video

Sanoculis is pushing forward its minimally invasive micro sclerostomy (MIMS) stent-less procedure. The surgeon inserts a specially designed cutting tool into the sclera and removes a small channel of tissue to create a drain and reduce IOP. MIMS was launched commercially in Israel and in Europe, said CEO and cofounder Nir Israeli. A postmarket study of 120 cases in Europe reported a 38% IOP reduction and an 85% medication reduction from baseline. The company aims to initiate a US pivotal clinical trial next year. The study would compare MIMS and standard trabeculectomy, with a planned US commercial launch in 2025. Link to video

Nicox is working on two nitric oxide-donating products targeting glaucoma as a follow-up to the 2017 FDA approval of its prostaglandin analog Vyzulta, cofounder, CEO and chairman Michele Garuli reported. NCX 470, designed to release bimatoprost and NO into the eye to lower IOP, is in two Phase III trials comparing once-daily 0.1% NCX 470 to latanoprost 0.005% in patients with open-angle glaucoma or ocular hypertension. Topline results are expected in 2023, Garuli said. NCX 1728, in preclinical studies, is the first in a new class of compounds with NO-mediated IOP-lowering effects enhanced by concomitant inhibition of phosphodiesterase-5 (PDE5). Molecules in this class have potential as monotherapy, adjunctive therapy, or in fixed-dose combinations with prostaglandins for IOP lowering, he said. Link to video

Exhaura, a spin-out from Trinity College in Dublin, is developing EXH-001, an investigational gene therapy for glaucoma. In preclinical testing, the product is designed to be a single injection that uses a novel mechanism called a molecular trabeculotomy, said founder Thomas Chalberg, PhD. EXH-001 is an adeno-associated virus gene therapy that encodes a matrix metalloproteinase, MMP-3—an enzyme that improves extracellular matrix blockage in the trabecular meshwork. It’s delivered intracamerally. Preclinical studies have shown the agent improves anatomy, increases aqueous humor outflow and lowers IOP with no inflammation or other toxicity, Dr. Chalberg said. The company next plans to move to dose-ranging and proof-of-concept studies in nonhuman primates, followed by toxicology and biodistribution studies to support an initial Investigative New Drug (IND) filing, Dr. Chalberg said. Link to video

PolyActiva has two ocular implants in development for sustained release of latanoprost, said CEO and founder Russell Tait: PA5108 and PA5346, both designed to release medication for up to six months, after which they degrade. The 2-mm PA5108 implant can be inserted in the inferior angle of the anterior chamber by clear corneal incision in the doctor’s office. Interim Phase IIa results showed PA5108 at 15 mcg was safe and well-tolerated. It persisted for at least 21 weeks and biodegraded in all subjects by week 40. It achieved 20% IOP-lowering at 12 weeks, with some subjects experiencing a greater than 40% drop in IOP, but with no persistent IOP lowering after the implant biodegraded. PolyActiva plans to continue the Phase IIa study of PA5108 and initiate the first clinical study with the second-generation PA5346 implant. PolyActiva is also developing additional products for glaucoma and postsurgical care, including implants for back-of-the-eye applications, Tait said. Link to video

iStar Medical expects European approval for its investigational MIGS device MINIject later this year and has begun enrolling patients in a US IDE trial called STAR-V, said CEO Michel Vanbrabant. STAR-V will enroll more than 350 patients with primary open angle glaucoma. The implant, made of anti-fibrotic medical-grade silicone STAR material, is designed to reduce IOP by optimizing the drainage path from the anterior chamber to the supraciliary space. The European STAR-I and STAR-II clinical trials found the device led to IOP reduction of 39% at two years. About 45% of patients had a reduction in medications and 46% were able to discontinue medications. The company also plans to expand its work to combine the MIGS procedure with cataract surgery in 2023 and expects US approval as a standalone MIGS procedure in 2026, Vanbrabant said. iStar is seeking €50 million (US $58 million) to fund the study, product development and commercialization in Europe. Link to video

Aerie Pharmaceuticals had a strong year, with 10,000 physicians prescribing Rhopressa or Rocklatan on a monthly basis, said Tom Mitro, president and COO. From July 2020 to June 2021, prescriptions grew by 119,000 at a time when overall glaucoma prescriptions declined by 911,000, he said. In Europe, Rocklatan was approved in 2021, following Rhopressa’s 2019 approval. Aerie is now focused on achieving approvals in Japan, the third-largest glaucoma market, Mitro said, and has conducted Phase II and Phase III trials of Rhopressa. In the Phase III trial, once-daily Rhopressa 0.02% lowered IOP by 4.7 mm Hg, compared with 3 mm Hg with twice-daily ripasudil 0.04%. The company also signed a licensing agreement with Santen to market the products in Japan and other Asian countries. Link to video

Avisi Technologies is pursuing 510(k) clearance for its investigational aqueous shunt VisiPlate, and is planning to raise $10 million in Series A funding to support clinical trials in the US, said Rui Jing Jiang, cofounder and CEO. VisiPlate is intended for patients with moderate to severe glaucoma who need surgery to sustain lower IOP. The ultrathin bottle-shaped implant is designed to drain aqueous fluid through multiple channels. Preclinical studies demonstrated sustained IOP-lowering potential and “excellent biocompatibility,” Jiang said. In a three-month animal study, the device achieved significant reduction in IOP from a baseline of 15 mm Hg; at some points, IOP reduction approached 40% from baseline IOP. A first-in-human clinical trial is ongoing, she said. Link to video