These days, “innovation,” “excitement,” and “new hope” are common keywords in articles about glaucoma therapy. As industry veterans know, that was not always the case. Glaucoma Physician sat down with Rick Lewis, MD, cofounder of Sacramento Eye Consultants and chief medical officer of Aerie Pharmaceuticals, to talk about the progress of glaucoma therapies through his nearly 40-year career and where his company’s pipeline drug, netarsudil, fits into that evolution.

Q. Your career has covered a great deal of ground in the clinical setting and in industry. Can you talk about that path?

A. I went to medical school at Northwestern, did my residency at UC Davis, fellowship at the University of Iowa, and worked in academics, private practice, and industry, performing clinical research for glaucoma products that are available now. When I left UC Davis and went into practice, eventually serving as president of the American Glaucoma Society, I continued relationships with industry and contributed to the development of topical drugs, sustained-release drug delivery, and minimally invasive glaucoma surgery (MIGS). When I took on the part-time position at Aerie a few years ago, that change was really part of the same continuum, of battling glaucoma clinically by pushing forward.

Q. Advances in glaucoma treatment have been headline news in recent years. What do these developments mean to you after nearly four decades in the specialty?

A. It’s remarkable. When I began treating glaucoma, we only had topical beta blockers, which affect the heart and lungs. When prostaglandins were launched with latanoprost in the 1990s, they transformed treatment. Suddenly, we could control pressure with a once-a-day drop that had none of the beta blocker systemic side effects. That option previously didn’t exist. Its safety and efficacy quickly made latanoprost the market-leading glaucoma treatment.

Fast forward another decade, and I was very involved in the development of MIGS devices. Trabeculectomy had long been (and still is) the gold standard for glaucoma surgery, but its short- and long-term complications created a desire for effective surgeries that were safer and less invasive. It’s the same concept physicians are applying to many different specialties, including neurology and cardiology. The results were the development of a subconjunctival option with Xen Gel Stent (Allergan), a canal space stent in iStent (Glaukos), and the suprachoroidal CyPass (Alcon). Surgeons can achieve the same or similar efficacy to trabeculectomy with a safe ab interno approach, and it opens the door for more candidates. We can’t overstate how MIGS is changing the treatment of glaucoma. However, the need for better, more specific medications to treat glaucoma is as great now as it ever was. Medical therapy for glaucoma isn’t going away.

Q. Aerie has two once-daily drops in the pipeline now, netarsudil 0.02% (Rhopressa) and a combination product of netarsudil 0.02% and latanoprost 0.005% (Roclatan). Will netarsudil represent another milestone in the treatment of glaucoma?

A. Before discussing netarsudil, it’s important to review its development history. The late Dr. David Epstein at Duke University envisioned a treatment for glaucoma that was directed at the source of the disease: the trabecular meshwork. He worked with Casey Kopczynski, today the chief scientific officer at Aerie, to screen molecules and found a few that worked in the laboratory. Together, they founded Aerie, and they spent more than a decade developing a compound for commercialization. Netarsudil is the fruit of those labors.

Netarsudil is the first of a novel class of drugs called rho kinase (ROCK) inhibitors to be developed for glaucoma. It would be the first agent since prostaglandins debuted more than 20 years ago to use a new mechanism of action for the treatment of glaucoma. Netarsudil appears to reduce IOP primarily by increasing outflow through the trabecular meshwork, the main drain for normal eyes. This has been demonstrated in both preclinical studies with the molecule and in clinical studies with topical ocular administration of netarsudil ophthalmic solution.¹

The NDA for Rhopressa was filed in February. We will likely file the NDA for Roclatan within the next year. Roclatan grew out of the question of whether a combination product could maximize IOP reduction. Earlier efforts to develop a combination product with a prostaglandin in the U.S. were unable to show sufficient efficacy over a prostaglandin alone to warrant approval. In a multi-center prospective study, the combination of netarsudil and latanoprost lowered IOP >1 mmHg more than either drug used alone. And neither netarsudil nor the combination product has demonstrated any serious or drug-related systemic side effects.

Q. Much has been written about MIGS revolutionizing glaucoma treatment, the idea being that safe, minimally invasive procedures can eliminate or reduce the need for drugs. Now Aerie may have a new drug. Where does that development fit into 21st Century glaucoma treatment?

A. As a surgeon who helped develop MIGS devices, I share my colleagues’ enthusiasm for the procedures. However, there is no surgery that makes IOP-lowering drugs obsolete. Drops are the first-line treatment for glaucoma. Although MIGS procedures have less risk than trabeculectomy or tube shunt, the lowest risk is still drug treatment. Furthermore, some patients aren’t candidates for MIGS, and even patients who have MIGS or other procedures often continue to need IOP-lowering drops.

Beyond filling the existing role of IOP-lowering medications, Rhopressa has been developed with the goal of offering better performance and compliance — the two goals that govern all glaucoma medications. The only proven way to treat glaucoma is to maximize IOP reduction in a way that’s easy and comfortable for patients to use. Moving to once-daily drops improves compliance. Currently, the prostaglandin is the class that is most frequently the drug of first choice; yet, many patients remain uncontrolled on a single medication. More than half of prostaglandin users require a second medication to help control IOP.² Our study of the combination netarsudil and latanoprost product has demonstrated additivity in phase 2 and phase 3 studies. This may allow patients to achieve better pressure reduction with one drop per day.

Q. Any turning point is a good place to look back and to look forward. What do you think about your long journey as a glaucoma specialist, and how do you envision the decade ahead?

A. Thirty years ago, I had patients using beta blockers twice a day and pilocarpine four times a day. Surgeries were crude, with high complication and failure rates, and we couldn’t control scarring. As a result, glaucoma was a very frustrating field. It was not innovative, and many ophthalmologists didn’t want to specialize in this disease.

Now, glaucoma is a very desirable field. We see multiple new approaches to diagnosis and therapy — an explosion of knowledge and of our power to treat the disease. It’s such a dynamic landscape today. We’re on the cusp of not only novel new IOP-lowering medications, but also of long-term drug delivery systems and MIGS-drug combination approaches. I think in the next 5 to 10 years, we will see more exciting breakthroughs.

I feel very lucky to have seen so much in private practice, academic practice and industry development, and now seeing the field develop and mature for the future. I think we’re just seeing the beginning today. I hope new ophthalmologists will be active and involved and keep moving the treatment of glaucoma forward. GP

References

1. Ren R, Li G, Le TD, Kopczynski C, Stamer WD, Gong H. Netarsudil increases outflow facility in human eyes through multiple mechanisms. Invest Ophthalmol Vis Sci. 2016;57(14):6197-6209.
2. Lichter PR, Musch DC, Gillespie BW, et al. Interim clinical outcomes in The Collaborative Initial Glaucoma Treatment Study Comparing initial treatment randomized to medications or surgery. Ophthalmology. 2001;108:1943-1953.