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Jay Duker, MD, spoke with Pharm Exec about advancements in ocular drug delivery.
Pharmaceutical Executive: How difficult was it to transition from private practice to corporate?
Dr. Duker: I actually wasn’t in private practice before joining EyePoint, but rather, was professor and chair of the Department of Ophthalmology at Tufts Medical Center. In many ways the transition was easy because I managed a large, diverse 150-person business at Tufts with an annual budget of more than $30 million. I am finding myself applying many of the leadership skills and insights from Tufts to my current chief operating officer (COO) role. For example, managing people, running the actual business, being goal oriented, setting strategic goals and operationally meeting them, and managing my time while juggling multiple parallel projects were all skills I that used in my previous role.
One of the biggest challenges in transitioning to the corporate side was learning the financial aspects of a public company. While I have a lot of ophthalmology relationships, I did not have much exposure to the market environment. Over the past year, I learned a lot about investor relations including an understanding of shareholders and becoming acquainted with key players like coverage analysts. It was really important for me to build their trust in what I was communicating about EyePoint–what we are doing and our plans looking forward.
I also look at things through a different lens. In my medical practice I am helping one patient at a time, which is always rewarding. Now, I look at an even bigger picture–seeing the impact of the approval of a new class of drugs that could potentially help hundreds of thousands of people–for example.
Pharmaceutical Executive: What advancements have been made in drug delivery for ocular diseases?
Dr. Duker: We have come a long way in treating ocular disease with pharmaceuticals. In the beginning all we had were eye drops. They were fine for the surface of the eye but didn’t penetrate deeper into the eye. Oral antibiotics and corticosteroids followed; both of which were effective but had limited utility and the potential for adverse systemic side effects.
About 50-to-60 years ago doctors began using intravitreal injections, initially in the setting of a severe infection called endophthalmitis. The advantage was targeted delivery with very little systemic absorption. Discomfort, along with the high frequency of treatment required for many diseases, proved to be inconvenient for patients. Once the Vitrasert Implant gained FDA approval in 1996, we had a sustained release local ocular delivery system with the ability to target treatment to the retina without systemic side effects.
Today, we are fortunate to have surgical ports, surgical implants, and intravitreal extended duration and sustained release devices that can deliver medication to the back of the eye. I see the technology continuing to advance toward fewer injections and inserts to increase tolerance and effectiveness without sacrificing outcomes, all while potentially lowering costs.
Gene therapy is an interesting area of innovation and an area that I believe holds promise for the future of ocular drug delivery. It should be noted that there are currently no gene therapies approved for use in the eye as drug delivery systems. Early efficacy data appears promising but, as an industry, we are in very early stages, and concerns about associated ocular inflammation need to be explored and addressed. However, I think that in the long-term gene therapy will be another solution for sustained release drug delivery in the eye.
Pharmaceutical Executive: What specific burdens do ocular diseases put on patients and their caregivers?
Dr. Duker: In areas such as wet age-related macular degeneration (wet AMD), there’s a huge treatment burden. The standard of care is monthly injections, which ties the patient to frequent visits to their retinal specialists in the long-term. Now we are seeing evidence that the societal disruption during the COVID-19 pandemic led to a decrease in treatment compliance in patients with significant retinal diseases, and this resulted in unrecoverable loss of vision for many patients.
At EyePoint, we are trying to thread a needle between reducing injections and visit burdens without sacrificing vision outcomes. We hope to deliver a sustained release anti-VEGF medication called vorolanib to the eye for at least six months or longer with a single in-office, intravitreal injection. This may cover patients who must miss visits and makes overall disease management much more convenient for patients and their families.
Pharmaceutical Executive: How are clinical trials for ocular diseases designed?
Dr. Duker: In general, drugs go through all three phases of clinical trials to gain FDA approval. Phase 1 looks primarily at safety, both ocular and systemic, in patients with the disease. If the safely results are acceptable, we also look for a suggestion of efficacy to go on to Phase 2. Phase 2 is a proof of concept with a larger population, generally ranging from 50 to 400 patients. There is also typically more than one dose of the investigational treatment in Phase 2 along with a control group that receives a placebo or standard of care for that disease. If Phase 2 shows a statistically significant outcome against the control group, the new drug will advance to pivotal trials or Phase 3, which in the U.S. is generally a minimum of two pivotal trials.
Phase 3 is also conducted against a placebo or standard of care using generally two doses on 300 to 900 patients, depending on disease.At this phase, studies generally last one year to determine efficacy but must follow patients for two years or more to ensure safety. While clinical trials are large, time consuming, expensive, and complicated, we look to them for better therapies and treatment advances.
Pharmaceutical Executive: What made you focus your work on ocular diseases?
Dr. Duker: That’s an interesting question. My dad had a very serious eye accident when he was eight years old and was blind in one eye. He was able to live a normal life but growing up I saw his experience with having somewhat limited vision and his concerns about the ever-present risk of potentially losing vision in his other eye.
When I got to college, I became fascinated with neuroscience in general, and the eye in particular. Then in medical school, I was impressed by how extremely complicated eye surgery is to perform. My subspecialty interest in retina was fueled by not only the precision the surgery required but the requirement that the surgeon be flexible and always thinking. No two surgeries are the same, and as a retinal surgeon, you really need to be comfortable with thinking on your feet (although we sit for retinal surgery). What really swayed me to ophthalmology and retina surgery is that I loved the big difference these procedures can make in patients’ lives.