Clearing Regulatory Hurdles with Dr. Kim Brazzell

Click here to watch the video version of this podcast.

Host Paul Karpecki, OD, FAAO, joins Kim Brazzell, PhD, chief medical officer at Kala Pharmaceuticals, to discuss his experience developing EYSUVIS, the first Food and Drug Administration-approved prescription therapy specifically developed to address the short-term treatment needs of people living with dry eye disease. Dr. Brazzell provides tips for navigating the approval process and shares lessons learned since he started working in the space. You don’t want to miss this episode. Press play now!

Would you like to be featured on our podcast? Click Get Involved to submit your information.

Transcript:

Paul Karpecki: Hello, welcome to the OIS Podcast. I’m Dr. Paul Karpecki practice in Lexington, Kentucky. And I’m honored today to have a special guest who just coming off some great success with the FDA approval of EYSUVIS. But really, today’s webinar really, or I should say podcast is really to take us through an understanding of kind of, you know, what Kim Brazell was able to achieve over the years, kind of his background where he grew up, I got there some insights and pearls around the entire regulatory process. And we have a lot of listeners that have key interest in this that you know, there’s been many dry eye drugs that have never quite made it through, and some are probably pretty good. So there’s a lot of understanding of the field of disease of this area. And we’ve had a perfect guest to be able to present. So welcome, Kim, great to have you here.

Kim Brazzell: Thank you very much. It’s a pleasure to be here and be with you, Paul.

Paul Karpecki: Thanks, give me we really could have just gotten together. We live about 10 minutes apart and like any other time of year, we could have done this, though. So yeah. Good point this a little better. Well said, Hey, Kim, you don’t mind, let’s briefly walk us through your personal background. Like even growing up, I know where you grew up your education kind of was your professional path into eyecare. And especially now, you know, leading regulatory for a public company in California.

Kim Brazzell: Well, I grew up in Kentucky in Western Kentucky a small town and worked in a pharmacy in high school so became a bit intrigued by drugs and how they act and you know how people develop new drugs and address some of the problems there what school to university Kentucky, both undergraduate and graduate. So I’m still a diehard Wildcats fan, although it’s not so easy this year. And my first job out of school was working at Hoffman LaRoche in New Jersey. More on the clinical pharmacology side. And after about five years there, I got a call from a professor who asked if I’d be interested in moving to Texas to Alcon. And I’ll be honest, I got into Acura not so much because of my interest in the eye but my interested in getting out of New Jersey. So I moved to Alcon and as a young scientist did a lot of various different things in the clinical area, the preclinical and clinical pharmacology. And it was back when Alcon was really becoming you know, major force in the arena. From Alcon I went to stores which was part of laterally at that point and ran, ran the r&d group there. Learned a lot on the device side as well as we were starting pharmaceutical side. We got bought, it was part of America home products, they are American Cyanamid they got bought by American own product. So I decided I didn’t want to be part of that. So moved from there to CIBA Vision in Atlanta ran the R&D in the US on the pharmaceutical side, ran clinical worldwide and CIBA Vision or CIBA and Sandoz merged to become Novartis. So I continued to run r&d in the US and then ran clinical globally. We got three products approved glaucoma, med vision done the first treatment for AMD people never think about that anymore. And then Zaditor which you may see at your local pharmacy now because it’s OTC. I moved on again. They folded the ophthalmic group into big pharma there and, and so I moved to Inspire Pharmaceuticals. I ran the ophthalmology R&D there. We were in both cystic fibrosis and ophthalmology. I think most people will remember ACSI, which we developed and introduced and became a major product. I also ran the business, the ophthalmology business there for a couple of years. We got purchased by Merck, and I went out and became a consultant. One of my clients was Kala Pharmaceuticals. And I liked the company. I like the technology. I like the CEO. So after a few months of that I got brought on they asked me to join full time, which I did. There, I run that, you know, the clinical group, the regulatory group, the project management group, medical affairs, all those sorts of things.

Paul Karpecki: A lot of hats you wear as CMO that’s for sure a major company.

Kim Brazzell: And it’s a lot of companies for only being in my mid 40s.

Paul Karpecki: Yeah, it’s impressive. I can’t imagine what’s gonna happen over the next 40 years? They’ve done it Really? Well, it really is, you probably learned a lot along the way you? Have you held CMO roles or less with the organization in R&D a number of times now, you know, it’s a tough question. But you know, what, what have you learned along the way, I kind of like that you wish you’d even known today, or you know that you know, today that you wish you might have known in the one of the first or second company, or maybe the third, or maybe when you first started running that level of Chief Medical Officer for one of these companies?

Kim Brazzell: Well, I think you know, a couple things I’ve learned is, first of all, you learn from your mistakes. And that makes me a very bright person. But I’ve also learned that you need to, you know, go back and dissect the mistakes that were made. And then as you approach everything new, and I urge my folks to do this, sit down and imagine, for example, a clinical trial, the day after it fails. And imagine what you would be saying, I wish I had done this, just to make sure you’re thinking about everything, because in clinical trials in the pharmaceutical world, you don’t get that many shots. I mean, you hit the primary endpoint, you gotta hit them, you have to design the trials. Well, so I’ve learned that you really a lot of thought goes into clinical design. And you have to not only come up with a design, but challenge yourself to try to understand what could go wrong, and try to mitigate that, before you start a trial rather than after

Paul Karpecki: make sense without giving away trade secrets. You know, you look over the last two decades, some someone has told me, you know, 1718 companies have tried this route of approval and dry eye.

Kim Brazzell: Or 23 or less Count?

Paul Karpecki: 23, without an only three approved to date with EYSUVIS. your drug being the most recent was the third? What did you see missing? What was or, you know, what, what did you see that others don’t didn’t see, besides, you know, dissecting previous mistakes and understanding it that allowed you to get this drug through FDA approval?

Kim Brazzell: Well, again, I had, I had a lot, I gained a lot of benefit from the past failures, and I was involved in one or two of those. And, you know, the couple of things I learned was, you know, particularly around symptoms, when we first started doing these trials, you would ask patients 20 questions rate, your burning rate, your steaming rate, your foreign body sensation, they’d have a list of 20 or so questions and and we did a post mortem when I was at inspire them a couple of our trials and talk to some patients in the trials. And they said, honestly, I got very confused, you know, I don’t know the difference in burning or steaming or grittiness, or foreign body sensation. So I was just checking the same thing. I think what’s happened over the years, is we’ve learned to, to utilize more global scales. For example, ours was fairly simple question of, how do you rate the degree of ocular discomfort. So we didn’t ask the 20 questions. We also did it in a on a daily matter on a daily manner, using a visual analog scale. And I think that helped too, because it helps you capture every day, how the patients are reacting, and allows you to sort of level out some of the day to day variability. So I think that’s been very important. And, the other thing is really understand the drug you’re you’re studying, understand what it does, and choose your endpoints appropriate for that, for example, we use the conjunctiva hyperemia as a primary endpoint we work in with an anti inflammatory drug. You know, hyperemia is a hallmark side of inflammation. So that was a logical choice to do that. And the last thing is, you have to work closely with the FDA. You have to listen, you do have to challenge but you have to listen, because they’ve seen a lot of these as well. And we, you know, in every program I’ve worked on, it sort of been hand in hand with the agency and and it makes it a lot easier at the end if you’ve talked with them from the very beginning.

Paul Karpecki: Makes a lot of sense. Yeah. Yeah. And I agree with you. I think the agency has been very fair about, you know, this is what’s required and you get to pre specify, we work with you. They have a good understanding of the disease, the lack of correlation between signs and symptoms, makes a key role. You know, I think also timeframe, you know, I guess makes sense with a steroid have a shorter term timeframe that I probably contributed to as well to really a great decision. So we have a lot of, you know, I’m noticing a fair number of ophthalmology and optometry colleagues that have looked at, you know, roles where their Chief Scientific Officer or looking towards CMO-type roles, what advice would you give to someone who’s just starting out that playing some roles in that area, but could have aspires to that maybe in a few decades, or however long they can gain the experience into something broader? Yeah,

Kim Brazzell: I think a couple of things is, first of all, to realize you can’t do it all yourself, and to get as good of people as you can around you. And not be intimidated by someone that has a different viewpoint or a different perspective. I think that’s very helpful. And you know, whenever you think you’ve got it figured out, then you’re probably wrong, you need to step back and talk with others and make sure you really have it, have it figured out. I’ve worked at, you know, large companies like Novartis, small companies like Kala we’re getting bigger, I think you sort of need to look and see which is which is the better atmosphere for you. Large companies tend to have more resources. And so you can potentially develop more small companies, I think you have more opportunity, you have more influence. small companies sometimes tend to work harder. So you spend a lot of energy, but they’re also very energizing in my experience. So I think it’s important when you’re looking at getting into industry to understand who the company is, and what it is you want to do, do you want to work in a big pharma amongst the bureaucracy and have a lot of support groups around you somebody that takes care of everything, or smaller companies where in many cases, you become a jack of all trades.

Paul Karpecki: You’ve done a good job and surrounding yourself to quality people makes a big difference. Any mentors along the way that kind of helped, and that are that you, you know, learn from to allow you to get to the success until the level you’re at today?

Kim Brazzell: Well, I’ve had numerous mentors, mentors that I would really call out I’ve had a lot along the way. And I’ve tried to be mentors to others as well. And so I think that’s important to find someone that can steer you, you know, along the way, and then be able to give back to the next person to, to help steer them as well.

Paul Karpecki: So awesome. EYSUVIS is a very exciting drug. And I’ve been lucky to get to prescribe it, and we’re having good success in clinic with it. It’s doing everything we expected it would do and, and giving that you know, short term sign and symptom resolution. So we the timing is perfect. It only had a few weeks now and it’ll obviously bite down to vote podcast airs, doctors have more experience. So where do you see this drug succeeding? The most in terms of because you have great R&D experience and knowledge. We also have a lot of clinical knowledge to just never worked. A lot of doctors, your insights are there. What do you see this drug most succeeding and we have a lot of listeners who want to understand the drug too even though they may have heard of it, it’s new to them being the only the third drug approved, and at this time a drug approved for signs and symptoms again, where does it fit in?

Kim Brazzell: Well start on a little bit about some of the highlights of the product. You know, it is very rapid acting, we see onset of action within a couple of days. The safety profile, it’s very good. I mean, this product was really engineered with college drug delivery technology, our goal was to be able to get more drug into the ocular surface to get you know, maximize the effect. But still, it’s loteprednol less stroke inside the to have less side effects. And I think we achieved that very rapid onset of action. We got a very good safety profile. I mean, the most common that we’ve seen in our trials was ocular discomfort or burning stinging only in about 5% of patients and basically the same as placebo. And if we look at LP elevations, there’s a number of ways to look at it. If we look at a number of patients that have an elevation of 10 go over 21 we only had .2% of patients that had that elevation. So that is a little backdrop where I say to give a little bit of an anecdote I suffer from dry eyes. And quite honestly, it took me a while to figure out exactly what it was but there were certain times in the year or when I was on the computer too much or traveling on an airplane with my eyes would really bother me a lot of burning, stinging all these things we used to ask. I initially thought it was allergies, so I put an allergy drops, they didn’t do much. So I was at a meeting when I was probably densifier. Yes, we Gary Fouts and explained it to Gary. And he looked at my eyes and pulled my eyelids down and said, Son, you have dry eye, and you’re probably having a flare. And then, as we develop this product, you know, my personal experience, it never bothered me enough to want to go on a chronic medication, if I would get these flares, five, six times a year. And I will always grip my way through it. It wasn’t, you know, wasn’t comfortable. But I wasn’t exactly ready to go on long term therapy because I knew the issues, I’ve tried restates and the burning and stinging and taking it every day. And so as we were developing this, after the first clinical trials, we really started focusing on that is a key use of the product. And we found out in a lot of our research, talking to patients and physicians, that 80 to 90% of the patients, we talked to whether they had continual symptoms of dry eye or not, but they were dry eye patients suffered from these dry flares. And many of them echoed, you know, what I just said, my thoughts were, they weren’t ready to go into chronic med or they took a chronic, one of the more chronic medications, and it didn’t work quick enough or wasn’t tolerated enough. And you know, within the first couple of weeks, their flare would go away. So they’re like, I don’t need it. So I think that’s one of the areas where this is going to have great utilization is those patients that aren’t well served with artificial tears, have these flares, And what to treat acutely? And I think that is a key area where I think we’ll see a lot of utilization.

Paul Karpecki: I agree with you, I think myself, I can relate to that. And clinically I have patients too who mention, or anything we can try besides going on therapy and film you’re getting four – six episodes, you know, that’s gonna play a role. The other thing is exciting, and I get crazy. Kim is that could be your earlier dry patient who just had the episodic episode, or could be the more severe chronic patient who is on chronic therapy, but still gets breakthrough flare up? Yes, you’re so

Kim Brazzell: in fact, in our research, what we found in talking to patients is that those that were taking Xiidra or Restasis, we started with a risk basis. And then Xiidra came out had as many flares and in general more severe flares than those that warrant so even patients that are maintained on one of the chronic medications do experience these flares, and what really.

Paul Karpecki: Makes total sense. So you know, you’re only the third company in this dry eye field to achieve what you’ve done and most recent, so I guess you’re finished with your work now. Yes. know, really, what is the next step for for a Kala? Is it just now focus on this great approval and all the utility and opportunities here? Are you already you know, looking at work next.

Kim Brazzell: We’re already looking at the next things, we have a couple of very interesting products in our pipeline. We’re working on some back of the eye products, one in particular a, a tyrosine kinase inhibitor that inhibits VEGF. And using our drug delivery system, we’ve been able to show an animal’s at least very good penetration from a eyedrop rather than injecting it in the back of the eye. We got very encouraging data, where we can get an animal’s similar levels that you see with the tyrosine kinase inhibitor inserts that are now being put in entry vitually. So we saw seen very good efficacy in animal models of CMV Corrado neovascularization similar to that you get with Avastin or Lucentis. So, we’re moving that into ind enabling studies to use a little lingo here. So that we’re hoping that in the coming year or so we’ll be moving forward with that. We’re also looking at a series of compounds we’re in a little earlier stage called segments, which are really selective inhibitors of glucocorticoid agonist glucocorticoid receptors and, you know, if you hit a glucocorticoid receptor with a steroid, you really, you stimulate two pathways one has been shown to be primarily responsible for the efficacy, the anti-inflammatory effect, the other pathway is been associated more with the untoward effects. And so we’re looking at molecules that are selective towards the good pathway, and not the bad pathway, we’d love to have a anti-inflammatory agent that and I think many have tried, but we’d love to have an anti-inflammatory agent that has the the anti-inflammatory effect of a steroid, but be devoid or at least have significantly less than the steroid side effects. And we’re also very actively looking at licensing opportunities. Now the company is in a very good financial situation, even without our service. And then as the service picks up, we’ll have funding for that. So we’re, you know, our goal is to build an ophthalmology company. And I think we got a good start, we got two products approved. We got two, three good programs in the preclinical state. So we’re looking to bring in an asset or two to kind of fill that gap.

Paul Karpecki: Very exciting, really wonderful. Dr. Brazzell a wonderful interview, really, I loved your insights regarding, you know, dissecting previous failures, so many people look at them as failures. And yet they’re really stepping stones towards you know, improving and getting to the next level I like the surrounding yourself with good people. Like the importance of looking at this smaller companies versus larger companies know where your personality might fit in. You’ve done all of them. So it’s terrific insight, and I certainly compliment you on very successful regulatory pathway for EYSUVIS, a very high bar, very few people have achieved what you’ve just achieved and exciting to see that the company isn’t going to rest just on the success but has a lot more in store for it. always learn a lot when I have the time with you. Kim, it’s a real pleasure. Thanks for taking time out of your very busy schedule and light of where you’re at and taking time to podcast.

Kim Brazzell: It’s been a pleasure working with you over the years and it’s a pleasure being with you today.

Paul Karpecki: Thanks Kim.

Kim Brazzell: Thank you