Glaukos Medical Corp. is slowly proving its stent used in the treatment of glaucoma can be used as a standalone therapy, dispelling the idea the device must be used in conjunction with cataract procedures. The San Clemente, Calif.-based company, which competes in the Micro-Invasive Glaucoma Surgery (MIGS) space, revealed hard data in the form of a 53 open-angle glaucoma patient study.

Results showed that Glaukos' Istent Inject Trabecular Micro-Bypass stent, combined with topical travoprost, delivered a 35 percent reduction in mean intraocular pressure (IOP) to 12.9 millimeters Hg after 18 months of follow-up. The results were recently published in Clinical & Experimental Ophthalmology.

The study has huge implications for Glaukos' Istent Inject, which is a next generation device designed to deploy two stents into separate trabecular meshwork locations for IOP reduction and procedural ease.

"We believe this study, and its positive results – both in terms of efficacy through IOP and medication reduction – and safety, further validates the company's Istent Inject platform," said Chris Lewis, an analyst with Roth Capital Partners. "Importantly, we note these results were experienced using a standalone procedure, helping to disprove the perception of some that Istent's combination with a cataract procedure is the key driver of IOP reduction."

The company is also evaluating a Travoprost intraocular implant with its Idose delivery system in a phase II Investigational New Drug (IND) trial. Implanted during a micro-invasive procedure, the Idose is designed to continuously elute therapeutic levels of a proprietary formulation of travoprost for extended periods of time. Travoprost is designed to increase outflow primarily through the uveoscleral, or unconventional, pathway, and to a lesser extent through the conventional pathway. When the implant's medication is depleted, the implant can be removed and replaced in a similar micro-invasive procedure.

Glaukos received initial FDA approval for the first generation of the Istent back in 2012. The device is inserted through the small corneal incision made during cataract surgery and placed into Schlemm's canal, a circular channel in the eye that collects aqueous humor and delivers it back into the bloodstream. Once inserted, the company said that the Istent improves aqueous humor outflow, while fitting naturally with Schlemm's canal.

Path to regulatory approval(s)

Glaukos is playing both sides of the field with the Istent Inject. On one hand, it is seeking to get FDA approval for the stent to be used in conjunction with cataract surgery, while it is also seeking approval for the device in standalone procedures. But the standalone indication could be further off for the 16-year-old company.

During a May earnings call, Glaukos President and CEO Tom Burns said the company was in discussion with the FDA regarding next steps for the standalone version of the device, which includes determining a study design for a 500-patient pivotal trial.

Switching gears, Burns said, "The Istent inject combo cataract pivotal trial is fully enrolled and farther along with the two-year follow-up concluding this August. We are already preparing modules for submission to the FDA with a plan to file our full PMA by year's end."

FDA approval could come some time in the second half of 2018 analysts estimate.

The device has CE mark in standalone procedures and has been a strong product for Glaukos outside of the U.S. It has resonated highly with the physician community in Germany and in Australia, where it has been launched, Burns said.

Burns said the company could see a greater penetration of Istent Inject in practices and the technology might attract some physicians that have been skittish about MIGS procedures. But the most telling aspect of the device is the path to reimbursement, which has mostly been established.

"We think there is enough headroom within the CPT code for us to establish a premium price which may also give us a little bit more ability to create robust growth with the new product line," Burns said. "For all those reasons, we remain very, very bullish on Istent inject, and frankly we think it will be a tough, tough product to compete against."

Larry Biegelsen, an analyst with Wells Fargo said the company could have smooth sailing when it comes to reimbursement.

"Based on our conversations with reimbursement experts, we believe Istent Inject will ultimately be reimbursed through the same category 3 code as first-generation Istent, meaning there will not be an incremental reimbursement benefit to the facility," Biegelsen said. "However, the Inject device involves the insertion of two Istents (rather than one), which we believe could result in a modest incremental benefit to the physician fee."

A tale of two (MIGS) stents

Glaukos' Istent Inject could gain approval and be launched around the same time its Irvine, Calif.-based rival Ivantis would have the Hydrus Microstent released on the market. In January Ivantis, a private company raised $25 million in series C funding to help support the continued development of the technology.

Ivantis' Hyrdus is made of a flexible, 8 millimeter long nitinol wire, which is much larger than the 1 millimeter Istent.

Biegelsen said that "while early data has shown impressive efficacy, we have heard from some physicians that Hydrus is more difficult to implant than other MIGS due to the larger size of the device."

Data from a pivotal trial of Hyrdus could come at the American Academy of Ophthalmology meeting in November.

"We suspect Ivantis' pivotal study could show modestly better IOP reduction vs. the Istent pivotal study," Lewis said. "However . . . any thought of Hydrus being more efficacious than Istent will likely be tempered with the launch of the potentially more efficacious, and more straightforward insertion delivery method with Istent Inject."

MIGS 6 (no more)

Glaukos and Ivantis are two of the six original companies in the MIGS space. However, half of the companies in the space have been acquired by larger firms. At one point, Glaukos was by far the largest of the six players in the MIGS space and was the first to go public, beating expectations by bringing in $108 million in an initial public offering in 2015.

Now, Basel, Switzerland-based Novartis AG and Dublin-based Allergan plc are the largest companies in the MIGS market. In February of last year, Novartis acquired MIGS player Transcend Medical Inc. and folded it into its Alcon division for an undisclosed sum. (See BioWorld MedTech, Feb. 19, 2016.) Novartis' Alcon received FDA approval in August of last year for Transcend's Cypass stent based off data from the COMPASS study. However, while Cypass is approved, it is expected to receive a CPT code effective July 1. Lewis said the device will still need to go through the 'heavy lifting efforts' to obtain individual Medicare Administrator Contractor coverage, which ultimately determines payment.

Other acquisitions in the space include Allergan picking up MIGS contender Aquesys Inc. for $300 million in an all cash transaction back in 2015. (See BioWorld MedTech, Sept. 8, 2015.) The deal closed in October of 2015. Aquesys' Xen stent has FDA approval, but initial traction for the devices remains limited, Biegelsen said.

"Management noted Xen is still in the early phases of a controlled U.S. launch focused mostly on glaucoma specialists," he said.

Osaka, Japan-based Santen Pharmaceutical Co. Ltd. made the third acquisition in the MIGS space when it said it would scoop up Miami-based Innfocus Inc. for about $225 million. (See BioWorld MedTech, July 20, 2016.) The deal closed in August 2016.

Outside of Glaukos and Ivantis Wavre, Belgium-based Istar Medical SA is the only other MIGS company that has not been acquired by a larger firm.