Diagnose Early, Stop Progression, Rehabilitate Vision

The new mantra of keratoconic care is: Diagnose early, Stop progression, Rehabilitate vision. Currently, in the stop progression category, there is only 1 FDA approved treatment to stop progression of keratoconus, corneal crosslinking (CXL). News of a potential new treatment would offer another option to stop progression.

In September 2017, a press release regarding the award of an SBIR grant to investigate a topical treatment for keratoconus hit the internet. “iVeena is pleased to receive a total of $450K in Federal Government grants to advance its portfolio programs,” said Gerald Simmons, CEO. “$225K is an NIH grant for its Keratoconus Orphan Drug Candidate. IVMED-80 is the first eye-drop, non-surgical, non-laser treatment for medical crosslinking of the cornea.”

Since the press release, many patients with Keratoconus and many doctors want a better understanding of the treatment and the timeline for its availability. To better understand the treatment, it’s important to understand the SBIR program.

The Small Business Innovation Research (SBIR) program, also known as America’s Seed Fund, is run by the National Institutes of Health. The SBIR program’s purpose is to provide early-stage funding to small businesses that have the potential to commercialize biotech innovations in the United States. To qualify, the business must be US owned and operated, participate in federal research and development, and develop life-saving technologies while creating jobs. The SBIR program is highly competitive and being awarded a grant is no easy feat.

However, being awarded an SBIR grant doesn’t mean that IVMED-80 had undergone and completed the regulatory pathway. It simply meant that iVeena was granted funds by the NIH to pursue research on IVMED-80… but what is IVMED-80? To understand the proposed IVMED-80 treatment, one needs to understand the relationship between keratoconus and LOX (Lysyl Oxidase).

Several papers over the past few years have reviewed genetics and biochemical components associated with Keratoconus. One of the many genes and biochemical enzymes of interest was Lysyl Oxidase (LOX). Two specific papers stand out on the topic: Bykhovskaya et al “Variation in the Lysyl Oxidase (LOX) Gene Is Associated with Keratoconus in Family-Based and Case-Control Studies” and Shetty et al “Attenuation of lysyl oxidase and collagen gene expression in keratoconus patient corneal epithelium corresponds to disease severity.” The conclusion of both is that underexpression of LOX, both genetically and biochemically, may lead to fewer crosslinks in the corneal stroma and thus may be a factor in keratoconus.

The proposed mechanism of action is that the topically delivered IVMED-80 is based on a cofactor for LOX activity and would upregulate expression of LOX, increasing crosslinks and thus stiffen the cornea. The SBIR grant will aid iVeena in the early laboratory investigation, to first prove in-vivo safety and tolerability in rabbits, then show effect in the form of increased crosslinks and biomechanical strengthening in rabbit corneas, and then test effect on ex-vivo human corneas.

Where is IVMED-80 currently? They have completed early in vivo animal studies and ex vivo human cornea studies. IVMED-80 showed effect by week 6 as seen on topography and OCT, they found an increase in biomechanical strength and corneal flattening in the animal model. In the ex-vivo model, the keratoconic human cornea was tested for increased LOX activity in stromal fibroblasts and biomechanical strength. This data will be presented at ARVO this year.  It is a promising start as iVeena looks to enter phase 1 trials this year. The big question remains whether IVMED-80 will be an ongoing medication or be used for a period of time and then discontinued with permanent lasting effect. Will it be used in conjunction with CXL? As a supplement? 

It brings to light several interesting areas for research and development for possible future treatments of keratoconus. Such as biochemical intervention for prevention and stabilization as well as genetic-based testing for early detection. LOX is just one of many potential factors in keratoconus. As practitioners, we need to keep abreast of research and development and possible innovations to benefit our patients.  It is important still to keep in mind that the only current treatment for progressive keratoconus is CXL and we need to utilize it.