SAN FRANCISCO – Kicking off the sixth annual Glaucoma 360-New Horizons Forum, co-founder and co-chair Adrienne Graves proclaimed that "glaucoma is hot." The meeting is sponsored by the nonprofit organization San Francisco-based Glaucoma Research Foundation (GRF). Attendance was estimated at 350 people, the most successful meeting yet.
For many years, the roughly $5 billion glaucoma market was moribund, with both the pharmaceutical and device side virtually devoid of any meaningful innovation. No significant new classes of pharmaceutical agents have been approved since 1996, when the prostaglandin drug lantoprost gained clearance. Meanwhile the device side has also languished with older technologies such as laser trabeculoplasty and relatively ineffective and/or highly risky surgical procedures like (trabeculectomy and shunts) being the mainstays in treating drug resistant or noncompliant patients.
Throughout the day, there were numerous signposts supporting Graves's assertion. For one, she noted that Bob Stamper, a long time GRF board member and renown glaucoma specialist from the University of California San Francisco (UCSF) told her recently that the quality of candidates applying for glaucoma fellowships at UCSF was the best he had ever seen.
An example of the tremendous progress in the sector is that there are now three FDA-approved minimally invasive glaucoma surgical (MIGS) devices. The first, dubbed the Istent, is sold by San Clemente, Calif.-based Glaukos Inc. It was approved in mid-2012 and has achieved stellar commercial success with worldwide revenue for 2016 estimated at $110-$115 million.
The second approved product, called the Cypass, was developed by Transcend Medical Inc. prior its acquisition by Fort Worth, Texas-based Alcon – a unit of Novartis International AG – in 2016. Cypass, which is placed in the supraciliary space rather than in Schlemm's Canal where the Istent is implanted, was FDA approved in July 2016. Alcon has recently launched Cypass in the U.S.
In his Cypass presentation, Steven Vold, of Fayetteville, Ark.-based Vold Vision, noted that this device provides a "novel outflow enhancement mechanism and ... has demonstrated superior, long-term efficacy and safety." Vold, who was a clinical investigator during Cypass FDA trial, is a big supporter of Cypass and told Medical Device Daily that he already has begun using it in his practice.
The third approved device, the Xen gel stent, gained FDA approval in November 2016 and will be launched shortly by its sponsor, Dublin-based Allergan plc. Xen was originally developed by Aliso Viejo, Calif.-based Aquesys, which was acquired by Allergan in October 2015.
Xen is implanted in the subconjunctival space and is targeted toward patients where previous medical management or surgical intervention has failed. According to Michael Robinson, vice president, Therapeutic Area Head–Anterior Segment and Consumer Eye Care at Allergan, more than 11,000 Xen stents have been implanted globally and his company is "eager and excited to enter the U.S. market."
Waiting in the wings are two other MIGS devices which are deep into their clinical trials – the Hydrus Microstent from Irvine, Calif.-based Ivantis Inc. and the Microshunt, developed by Miami-based Innfocus and now a part of the Osaka, Japan-based Santen Pharmaceutical Co. Ltd.
According to Brett Trauthen, Hydrus's chief scientific officer, its MIGS offering is the "only device that dilates and reconstructs the primary outflow path of the eye (Schlemm's canal)." It also provides scaffolding access to multiple collector channels.
Hydrus's international clinical data have been outstanding. In the U.S., Ivantis completed enrollment in its 558-patient FDA pivotal trial in mid-2015 and the two year follow-up data is expected to be released in November, at the annual meeting of the American Academy of Ophthalmology. Final FDA approval is very likely in 2017 or early 2018.
Meanwhile, Innfocus will complete its pivotal trial enrollment by midyear and then begin a mandated FDA one year follow-up, suggesting that its FDA approval will likely come in late 2018 or 2019.
Innfocus CEO Russ Tenary said that whereas "our competition is mainly focused only on the niche cataract with glaucoma market (approximately 10 percent), we are focused on the far larger total glaucoma surgical market." He estimated this is about a five times larger opportunity than concomitant cataract surgery alone. He added that the Micoshunt will be "the first FDA approved minimally invasive stand alone procedure for mild, moderate and severe stage primary open angle glaucoma.
MARKET POISED FOR MAJOR GROWTH
The entire MIGS market is poised for explosive growth. According to Bill Freeman, an ophthalmic industry consultant from St. Louis-based Market Scope, the MIGS market could reach $900 million (900,000 units) by 2021, up dramatically from $100 million (110,000 units) in 2016. Market Scope is also forecasting that the global glaucoma device market will soar from $354 million in 2015 to $1.1 billion in 2020. This represents a hefty compound annual growth rate of 26 percent.
It has been widely appreciated that the compliance rate for glaucoma medications is dismal, with less than 50 percent of patients still using drops after one year and 60 percent of glaucoma patients not using their drops properly. This so called "lack of adherence" is strongly correlated with vision loss and thus there is huge interest in new methods of glaucoma drug delivery.
Chris Muller chief commercial officer of Austin, Texas-based Mati Therapeutics, said that like many of the competing drug delivery technologies, his company is reformulating active ingredients from existing eye drops in a proprietary delivery system. This reduces regulatory risk and can speed the product to the market.
ACCELERATING GLAUCOMA RESEARCH
One of the most enlightening talks here came from Jeffrey Goldberg, professor and chair of the Stanford, Calif.-based Byers Eye Institute, Stanford School of Medicine. Goldberg is one of four scientists that are receiving funding from GRF through its highly innovative Catalyst for a Cure program.
The goal of Catalyst for a Cure is to accelerate the pace of glaucoma research. Entirely funded by GRF and its donors, it has brought together scientists from different backgrounds to work collaboratively to understand glaucoma and find ways to improve treatment and ultimately cure this blinding disease.
Goldberg's presentation, titled "The Future of Glaucoma Diagnosis and Treatment," discussed the biomarker initiative of the program and provided a very encouraging update on its progress. A few years ago, Goldberg began a small single site, investigator safety-oriented pilot trial, testing the Cumberland, R.I.-based Neurotech Pharmaceticals Inc.'s NT-501 device.
NT-501 is an intraocular implant that consists of human cells that have been genetically modified to secrete ciliary neurotrophic factor (CNTF). CNTF, which is a growth factor capable of rescuing and protecting dying photoreceptors, is delivered directly to the back of the eye on a controlled, continuous basis.
The preliminary results have been very encouraging, with solid safety demonstrated, along with indications that CNTF can promote optic nerve regeneration. It is the damage and eventual death of the optic nerve that ultimately causes blindness from glaucoma.
A phase II evaluation of CNTF for vision restoration in glaucoma will begin shortly at Stanford University. The goal of this trial is neuroenhancement through boosting the efficacy of the dying – but not yet dead – retinal ganglion cells.
The study will include biomarkers, which are required to measure and accelerate the development of candidate therapies. Advanced biomarker imaging will also be included in these studies. The first data is expected in late 2017.
Goldberg concluded his talk by saying that the long term goals of this research are threefold: Neuroprotection, neuroregeneration and neuroenhancement.