Vial Presents: Challenges in Retina Clinical Research featuring Dr. Nancy Holekamp

Dr. Nancy Holekamp, Director of Retina Services at the Pepose Vision Institute and Principal Investigator at the Midwest Vision Research Foundation, sits down with Marcia Swank, Vial’s VP of Ophthalmology, to discuss the current challenges for investigators in retina clinical research. Follow Vial on LinkedIn for to stay up-to-date on our latest conversations.

Marcia Swank: Hello, everyone. My name is Marcia Swank, VP and Head of Ophthalmology for Vial. Today, I’m really excited, and I’m here with Dr. Nancy Holekamp, who is our most recent member of Vial’s Scientific Board of Advisors in Ophthalmology. Part of our Ophthalmology therapeutic area launch, Vial is established this advisory board in order to get feedback in the field of Ophthalmology.

And Vial’s working really hard to reimagine clinical trials. And what better feedback to obtain than from our most trusted investigators. Dr. Holekamp joins Dr. Arshad Khanani and Jeffrey Heier. and I’m very excited to have you here today, with us, Nancy. Would you mind giving an introduction of yourself?

Dr. Nancy Holekamp: Thank you, Marcia. It is really my great pleasure to be here, to talk to you today. For your listeners, my name is Nancy Holekamp. I am Director of Retina Services at the Pepose Vision Institute, in St. Louis, Missouri. And I am also Principal Investigator at the Midwest Vision Research Foundation.

And in my career, I’ve been part of more than 38 national, randomized clinical trials, looking at some of the most important diseases in the retina space, such as macular degeneration, diabetic macular edema, retinal vascular occlusive disease, and others. So it’s really my pleasure to be here, today.

Marcia Swank: And, wow, we are just so excited to have you. So I’m just gonna dive right in Dr. Holekamp to some of my questions. Let’s say a new biotech approaches you. They have a great new asset and are gearing up for their first clinical trial. What advice would you have for them?

Dr. Nancy Holekamp: Marcia, what I would tell them is, lead with science. Amazing technology, new science, that generates tons of excitement and tons of momentum on its own. So if you have a really good new asset, it should really speak for itself.

But after that, there are important steps as well. And the second important step for people is to develop relationships. Biotech has to actually develop relationships with their principal investigators, with their clinical trial sites, because, at the end of the day, it all happens with the boots on the ground, and you really want to have people feeling connected, not only to your science, but also to your mission.

Marcia Swank: That’s so great. It speaks to the exact purpose for why we’re trying to do what we’re doing here, at Vial. Many biotech sponsors are obsessed with ensuring their trial recruits well. What have you seen work in recruiting, for trials that you’ve been a part of?

Dr. Nancy Holekamp: First of all, I like the word, “Obsessed.” Because biotech sponsors should be obsessed. Recruitment is just so important. And I have two pieces of advice. The first is to develop protocols in conjunction with your advisors and your doctors, so that the study visits are streamlined, with reasonable limits of testing.

Because nothing drags a clinical trial site down than a four-hour office visit, with lots of extraneous data collection procedures, particularly in older A&E patients, or diabetic patients that get low blood sugars around lunchtime. So I really want to stress talking to the investigators, people with experience, about… what’s the most important data you want to collect in this clinical trial? So that’s the first piece of advice.

The second piece of advice I have is … give incentives for a clinical trial site to get their first two patients into the study right away, because as soon as you’ve done one, and then another patient, then the whole clinical trial site knows how this study is gonna work. And they… the rest of the recruitment will just flow from there. I tell you, the first one or two patients are the hardest. So really provide an incentive for that.

Marcia Swank: That’s such great advice. You’re a really well-known figure on the podium, at many conferences. And we see the changes in the field, up close. With all the recent progress, what’s the most exciting development in retinal research that you didn’t expect?

Dr. Nancy Holekamp: Has to be gene therapy. The fact that the first FDA-approved gene therapy in all of medicine is in my field, of retina. We’re just a fraction of Ophthalmology, and Ophthalmology is just a fraction of medicine. It shows you how exciting this research field is, and how monumental it was to get a gene therapy to work for inherited retinal [00:05:00] degenerations.

And now, that groundbreaking research just opens up the field for all of these other gene therapy clinical trials, and we’ve actually taken that science and adapted it beyond inherited retinal degenerations, but also to wet macular degeneration, diabetic retinopathy, and diabetic macular edema.

So I am very excited about all of the work being done in gene therapy. But there’s a second thing that I didn’t expect. And I’m really interested in this suprachoroidal injection technique. And I really feel that this potential space for delivering therapeutics was almost found by accident. And it has some significant advantages. At least, we’re hoping they have significant advantages. And we’re trying to prove it.

But I’m very excited about combining gene therapy with the suprachoroidal injection approach, and I’m a cheerleader for all technology. I’m hoping that this works out well. But of course it’s up to us to prove the benefit, not only to patients, but to our field.

Marcia Swank: We’re in very exciting times right now, with gene therapy, for sure. So I am right there with you. Let’s fast-forward, and let’s say the year is 2027. What is everyone talking about in retina research circles? Places such as ASRS, or at Arshad’s Clinical Trial Summit. Is it still gene therapy, or do you think it’s gonna be something else?

Dr. Nancy Holekamp: 2027 isn’t too far away. I think the year coming up is gonna be 2023, so we’re talking… that’s only about four and a half years away. I think we will still be talking about gene therapies. Gene therapy is still early-days. We still have two very large hurdles, with gene therapy. One is retinal toxicity. Some of those pigmentary changes that we’re seeing in the retina. Another one is inflammation. We will certainly not only be talking about drugs, but we’ll be talking about drug delivery. So those things will go hand-in-hand, moving forward.

But I really think a larger proportion of our meetings is gonna be taken up by artificial intelligence. As a tool in our field. And I think we will be ground-breaking again, in this regard. The first artificial intelligence, FDA-approved, is also in my field. It’s in diabetic retinopathy. And now, we have a second AI technology approved in my field.

So I really see big data, digitization of data, artificial intelligence, machine learning, deep learning… All of these things, coming together in our field. And we’re gonna be talking about it at our major meetings, certainly by 2027, if not before.

Marcia Swank: And I think, with COVID that just really, just, leapt and took fire, in terms of artificial intelligence. As, as unfortunate as it was, it just caused us to look in a different direction, in how to make things better. And really looking forward to seeing what comes out of that. 

Dr. Nancy Holekamp: Can I can I just dream a little bit beyond 2027?

Marcia Swank: Sure.

Dr. Nancy Holekamp: Here’s what I, here’s what I see the future of my field being. I think that retina specialists will end up treating every single type of ocular disease with long-term drug delivery to the posterior pole. So I think we will be treating glaucoma, for the glaucoma specialists. I think we will become a drop-less society, where we will be using long-term drug delivery, for chronic diseases such as glaucoma.

I think that we’ll be treating presbyopia, cataract prevention, and be more aggressive about treating diabetic retinopathy, all from the posterior pole, all from retina specialists. And of course, this will require retina specialists to be engaged in this type of research, in the distant future.

Marcia Swank: Wow. That sounds amazing. We’ve always loved speaking with you about clinical trials and challenges faced by sites, and by sponsors. I want to dig into the specific challenges you think are most acute, and where a company like Vial could have the most impact on. So what are the largest pain points, at a site level, that you see, where we should focus… on our time and resource?

Dr. Nancy Holekamp: Right now, we’re all going through a period of time that we call, “The Great Resignation.” [Laughs] People are resigning left and right. I think we can blame the pandemic. It helped people put life into perspective. A lot of people are choosing not to work anymore. A lot of people are choosing to work remotely or at home, and as our jobs don’t lend themselves to remote work.

Staffing, is probably the number one challenge. Not only for our clinics, but for our [00:10:00] clinical trials, for our clinical trial units. After that, I think another challenge is just keeping up with the mountain of paperwork. In my current clinical trial unit, I’ve been there for over 10 years, and I have seen a logarithmic growth of the paperwork that’s required. I even come in on weekends now, to make sure that I can get through all the paperwork. So I think that’s going to be a real problem, moving forward.

Along with all the paperwork, I think there are a lot of inefficiencies of our current CROs monitors, all the people that we interact with, the vendors. I think there are a lot of redundancies and a lot of inefficiencies, where my clinical trial staff and I look at ourselves, and we say, “Wow, didn’t we just do this?”

I think another major challenge for everybody in clinical trials is recruiting more minorities into clinical trials. This was… This issue was presented by Vivienne Hau, at the ASRS meeting in New York City, in the summer of 2022. And she really exposed what a poor job we’re doing of having our clinical trials mirror the patients that we’re treating. And I think we really have to emphasize a new and different approach, so that we can be better in this regard.

Those are the ones that are top-of-mind for me, but as clinical trial work is definitely hard work. It takes real dedication, and there are challenges and troubleshooting on a daily basis.

Marcia Swank: And I think that’s all very excellent advice. Thank you. You’re a great mentor to many in the field, and I’m sure you’re asked by younger colleagues about how they can get into research. What advice would you have for them, on getting into research, and what it takes to build a successful research practice like yours?

Dr. Nancy Holekamp: First of all, I tell them, “Absolutely, do clinical research.” the practice of medicine is doing the same thing over and over again. But research is actually creating something new. It moves the field forward. It places you on the cutting edge. But it is a huge commitment of time, resources, staff. And you really have to love it.

And it will, necessarily, compromise your clinical practice a bit. You can’t see 90 to 100 patients a day, and still have time to talk to patients, develop relationships, explain randomization or what a placebo is to patients. These are very important concepts that patients must understand for informed consent, before entering a clinical trial. And you really have to be dedicated to taking the time to, getting patients into a clinical trial.

You also can’t be traveling to five different offices during the week. You have to be at a main study office. And you have to be at a main study office when there is a co-investigator, for those masked and unmasked investigator roles.

Once you have committed and set up your practice, your staff, your facility, for success, it’s so important to find a mentor. Because no one teaches you in residency, your fellowship, really, how to do clinical trials. And I really recommend that people who are just starting out go to all of the investigator meetings. All the time. Because you will learn how clinical trials are done at a very high level. You’ll make friends among the other investigators. And actually you’ll have fun too. That’s my advice for anyone who wants to start out in clinical trials.

Marcia Swank: [Laughs] Thank you so much. That was a great answer. I think, lastly I would just like to know… with all the changes you know that Vial is trying to make, and how we’re trying to reimagine clinical trials, and fix what we feel has been broken in the past, probably, decade, what are you most . excited about, in working with Vial?

Dr. Nancy Holekamp: I am very excited about working with Vial because the work we do in clinical trials is hard work. And I think Vial’s vision is to make that hard work easier for us, so that we can do a better job, and we can be more successful in our clinical trials. I am very much looking forward to the partnership, and very excited about the future.

Marcia Swank: Nancy, it was a pleasure speaking with you today. And I look forward to working with you much more in the future. Thank you so much.

Dr. Nancy Holekamp: Marcia, thank you. It’s been really fun.