Dr. Arshad Khanani, Director of Clinical Research at Sierra Eye Associates, sits down with Simon Burns, CEO and Co-Founder of Vial, to discuss the latest advancements in ophthalmology clinical trails.
Simon Burns: Thank you for joining us, Dr. Khanani. You are a very well known figure in the ophthalmology research space and it is a thrill to chat with you today. I’m Simon, CEO and co-founder of Vial. Vial has set out to reimagine clinical trials and with yourself and a series of scientific advisors, have designed a model that is both more advantageous to sponsors in running more efficient trials that are faster and- and doing that with- with technology and a phenomenal team of clinical operations leaders as well as better foresights, reducing the burden placed on sites.
Dr. Arshad Khanani: I’m Arshad Khanani. I’m Director of Clinical Research at Sierra Eye Associates. I’m a surgical and medical retina specialist. My real interest is running clinical trials from early stage to late stage. Molecules and delivery systems and gene therapy for retina, and I’m excited to be here.
Simon Burns: Dr. Khanani your name comes up time and time again. You’re incredibly respected both on the sponsors side as well as the- the PI side. Um You’re at the top of your field. What keeps you excited about the future of- of retina?
Dr. Arshad Khanani: Absolutely. Being involved in research, even when I was in training and founding the clinical trial department here at Sierra Eye Associates a decade ago, I’ll tell you the exciting thing being a PI for clinical trials is. When you start trials at an early stage and then you see the progress of those trials and then you take it to pivotal and then the pivotal trials read out positive, and then you have that product on the market. So over the last decade, we have been involved with multiple products that actually are currently available to help our patients. The first one was Rolicizumab that got FDA approved a few years ago, and then recently the approval of the suprachoroidal delivery system, as well as Faricimab. And, those two products we were involved since the early days and involved in many of the aspects of learning and designing the trials.
So it is really rewarding that now you’re involved with a program and, you can offer this treatment to your patients and they ask you what are your thoughts and you can really say that I’ve been involved with this program for last eight or 10 years and now this product is benefiting the patients. So that’s why I love clinical research, because, yes, many things fail, but as long as we execute the trials properly and do the right thing, I think we will have new products coming. And there are some geographic atrophy products that are likely going to get approval in the near future, and we’ve been involved in those trials, also.
Simon Burns: Exactly. And what are some of the mistakes less experienced investigators make? What advice- I’m sure lots of PIs come up to you asking for advice. What advice do you give them on how to do research and- and get into the field?
Dr. Arshad Khanani: Well, I think there’s several things that investigators should keep in mind, especially my colleagues and my younger colleagues, who really want to be involved with clinical research, is, first, to make sure that the trial brings value or the product brings value to your patients. Because our job is to move the field forward, not backward. For example, for me, I would not get involved in a phase I study where I’m not convinced about the safety of the molecule. I want to see the pre-clinical data. I need to see the TOPS data. I want to make sure that I’m not harming my patients, but rather helping them. And then the question is, what is this product going to mean to either the patients that are enrolled in this trial or in the future. Some of the phase I’s don’t benefit the patients that are participating in it, but there’s hope for patients in the future. So my advice would be that many investigators just sign up for as many trials as they can without looking at what that product is bringing for your patients and for your field.
And then the second thing is, many investigators just sign up for all trials. I think, I don’t work with companies that I don’t know much about. I don’t want to work with CROs that I don’t like, because what that does is that just puts layers and layers of extra work, because we know that with our experience with that certain CRO we didn’t like and the monitors were bad and, all the operation piece was bad. So I pick trials based on that and then, you know, don’t pick trial for the same indication and you have 10 trials for same indication, and now you’re not enrolling in many of them, or if enroll one patient in each, that just increases the work and that makes the site look bad.
So all of those things are important as you look at [00:05:00] trials, and that’s the advice for the investigators. Pick the trials that will help the patients. Pick the trials that is run by CRO that you enjoy working with, and then pick the best so that you don’t have multiple trials for same indication.
Simon Burns: Would love your take on all the recent data we’ve seen in gene therapy on the AMD side, DME side. Lots of excitement. Lots of people talking about it. I’m curious to get your perspectives. What do you think this means? What’s the future of gene therapy and is it practicing in any way for you?
Dr. Arshad Khanani: Absolutely. So when you look at gene therapy overall, it’s a very exciting field and. We’ve been involved with trials with subretinal delivery, of RGX314 we have been involved with trials uh, with intravitreal delivery uh, with ADBM022, as well as 4D150. These are intravitreal gene therapy agents, and I’m talking about neovascular AMD right now. And then we have the, suprachoroidal delivery, as you mentioned that is very exciting. We saw the first FDA approval for suprachoroidal steroid injection, Xipere, for uveitis associated macular edema. So the space is now validated, meaning that drug delivery in that space can benefit patients.
So, being part of the suprachoroidal trials for neovascular AMD, the ADA study, as well as diabetic retinopathy, the LTU study, what we are trying to gauge is the fact that can suprachoroidal delivery give us enough efficacy that we can have better safety profile compared to, let’s say, intravitreal gene therapy. Intravitreal gene therapy works great. It’s just that you still have to refine what the prophylaxis is going to be and, how long to treat patients with steroids, whether it’s systemic, intravitreal, topical, because the efficacy is great, and we’re still working on that. But suprachoroidal gives you this compromise between going to the orb with subretinal delivery and having the inflammation issues that we have seen with intravitreal. So it is exciting space.
You know, so far, we have seen data to really decrease treatment burden in patients, but there are still patients who have required supplemental injections to maintain anatomy. So we are still dose escalating. The other thing is, we have noticed inflammation in about 20% of patients as of the last data kit, but this inflammation is different than intravitreal gene therapy. It’s milder in that stance, but we are still considering should we have prophylaxis or not. So there’s a lot to be learned, but I think gene therapy really holds promise in terms of management of neovascular AMD as well as diabetic retinopathy in the near future. And suprachoroidal route is, it’s very intriguing and it makes sense to provide gene therapy in clinic and not expose the front of the eye with, to gene therapy like we do in intravitreal.
So we continue to learn together. We’re not there yet, but hopefully we’ll get there in the near future.
Simon Burns: On that topic, you’re very engaged in creating case studies, reviewing clinical trial data. Your team is also a very huge part of why that’s been so successful. I hear they’re very empowered and- and very active in the research. They all know the trial results and the information for subjects just as well as you do. Tell us more. How do you engage your team? How are you so active in that aspect? Research, educating others, educating your team and in particular, how do you lead and empower your team to be successful?
Dr. Arshad Khanani: I think that’s a very important point, because if you don’t have a good team, you’re not going to be successful. Clinical trial sites that are successful obviously need a very involved PI, but that’s not it. So I’m very involved. You know, I talk to all of them. I appreciate on a daily basis the hard work they put in, whether it’s the BCVA technician to the photographers, to coordinators, to coordinator assistants. I think my advice is that many PIs forget the fact that their success depends on their team, and I think appreciating the team on a daily basis and also, communication is the key with them. But, you have to find the patients, you have to talk to the patients, and then your team needs to know the protocol, the trials. They need to work well with the CROs. They have to work well with the sponsors.
So it takes time to build a good time, but our success depends on your partnerships. You know, whether it’s industry, whether it’s my team members, or whether it’s CRO. For example, Vial and our partnership for the Truckee Study. Truckee Study has really taken off in terms of our real world experience with um, Faricimab or [inaudible 00:10:50] patients with neovascular AMD, and now people around the world are actually paying attention to it. And that could have not been possible without working with Vial as well as working with all the PIs around the country. So I [00:10:00] believe truly in teamwork and I think, and the best way to do it is to communicate and, really appreciate everybody’s role in it. And I think we can only move the field forward if we all work together.
Simon Burns: We hosted a panel with yourself, Dr. Kaiser, Dr. Heier. You did a discussion about the challenges in clinical trials. We talked about the challenges your site directors face. We talked about the challenges in contracting queries. Give us one click deeper there. What are the challenges that you see are the most pertinent and most challenging in reimagining clinical trials?
Dr. Arshad Khanani: Absolutely. There are multiple examples to go, into. I’ll give you an example recently in a trial that you know a, CRO reported a deviation or a major protocol deviation to the sponsor and the sponsor logged it. While, when I saw that, I, I said, “What was the real reason?” And there was clear miscommunication between the CRO and the sponsor and the CRO didn’t communicate with us what they needed and the monitor that was before the current line to already address that. So I think there is a lot of lapses currently in operations of clinical trials from monitors that keep changing every few weeks or few months. And I think if you have a solid remote monitoring technology, where the consistency of monitoring is there providing high, quality monitoring while avoiding the burden on sites where we have to get ready for each monitor and answer questions and teach the monitors about what they are doing and what that was done in the past, I think it will be really meaningful.
The other issue is the, data cleaning efforts, and I’ll tell you a recent example where we got hit with 300 queries by a CRO for a database log that was happening for an earlier stage study. And, they’re telling us how to report adverse events and what is a significant adverse event, what’s not, and if it’s not significant we don’t want to report it and change of source and change this. And I stepped up and I talked to the sponsor and I said, “You need to talk to your CRO and make him understand how clinical trials run. Any new event is an adverse event, whether it’s clinically significant or not. We still have to report it.” So somebody very new was looking at the data and tagging it. So, guess what? From 300 queries, we went down to 18 queries without us addressing any one of them, because we communicated with the sponsor that the CRO it’s, really flagging things that, are incorrect.
So imagine if I was a site that I didn’t have the connection or communication with the sponsor. My coordinators will quit, because they have to do 300 queries within a period of a few days, and that’s what my coordinators said, that they’re going to make me quit with these queries, because they make zero sense. So I think this is the problem. If, the CRO and the sponsor and the sites communicated well, if we would have been notified that we’re going to flag this, we could have just said that we, don’t think this is the thing to flag and, cut down the work. So I think having more streamlined monitoring, open communication, will help sponsors as well as sites to really run clinical trials more efficiently.
Simon: Super spot on point. Totally agree. By the way, we really appreciated your support in getting the word out about our new model and and getting both sponsors and other PIs involved in the discussion of what it could mean to reimagine trials. And I think you’ve commented before that no one’s happy with the way that things are now. But maybe let’s talk about what- what could be if we were to bring together investigators who were to build a platform whether it’s technology or people or some combination of the two to enable better research. What could that mean for the field?
Dr. Arshad Khanani: Yeah I, think there is a big unmet need in our space for having a CRO that really caters to sites and sponsors, and I think to really streamline clinical trials. So when I heard about Vial and about the vision, I think I was very excited to hear that somebody’s paying attention to the problems we see on the operations side, on the executions side, on the communication side. And, I think if you can really help those, the burden to the sites and sponsors will really be exciting in terms of reducing the burden, so that we can do more trials. We only have that much capacity.
And, when I talk to my fellow investigators, and some of them are part of your scientific advisory board, there was not a single person said, “Oh, this is a bad idea.” Everybody said, “We have been waiting for something to [00:15:00] happen. We have to revolutionize the technology. We can’t use the technologies at 30 years old.” Whether it is monitoring, whether it is data entry, whether it is budget negotiation, whether it’s site payment. We are still very primitive in clinical trials in terms of how those processes are and that really takes a lot of time and in the end, everybody ends up spending a lot of time and revenue to make it better.
So having sites that are really looking to, as you call, reimagining clinical trials, they want to partner with Vial as a CRO, because we all want to do trials in more efficient, highly accurate and, really positive execution. So I think it’s really exciting for me to be a part of Vial, because I’m here to help the field move forward and, really the big unmet need of having a CRO that really uses the best technology. It really is sponsor and site friendly. It’s going to really help us move our clinical trials programs forward and more efficiently, so that new products can come out for patients sooner than later. So that’s why I’m super excited to be a part of as an advisor to Vial.
Simon Burns: Thank you. As we think about reimagining clinical trials to be more more beneficial for sponsors and sites what are the gaps we should be focusing on? And, in particular, what advice do you have for the Vial team that focuses day-in, day-out on, proving or reimagining trials?
Dr. Arshad Khanani: Yeah, Simon, that’s an excellent question. I think when I look at the space and what Vial is doing it’s, really exciting for all of us. You are partnering with the top KOLs in retina, the biggest clinical trial sites, as well as biggest clinical trial list in terms of designing the trials and helping sponsors execute trials. So I think the biggest gap is communication, as I said, and I think Vial is really doing everything from start to finish. So you’re starting with key advisors who know how the space works, and then you’re partnering with sites that are high end rollers, they are well respected. And then you’re helping the sponsors by introducing the highest level of execution in terms of the best technology, whether it’s EDC, whether it’s remote monitoring, whether it’s recruitment.
And then from a site level, having teams that are very experienced, building the team that really knows the space. It’s, also an unmet need, where we get monitors and operation people that have never done retina, and retina is very different than, let’s say, oncology. So I think you’re doing everything right and I hope that you are able to successfully execute many trials in the future for our space, so that we can have new products available for our patients sooner than later.
Simon Burns: Truly great, Dr. Khanani. What we like to ourselves is in order to have a phenomenal company you need to reimagine the space in some way, and then you need the expertise to get it right. And, that’s certainly true in, retina trials. And so we’re thrilled to have you as an advisor alongside other leading KOLs, and the future is bright for what we can do together, starting with Truckee and the real world evidence data capture that that, the trials are running and continuing on into other trials. So thank you for the time today and it’s a thrill to, to partner together.
Dr. Arshad Khanani: It’s my pleasure to be here and to work with all of you. Thank you.