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Zach Klaassen: Hi, my name is Dr. Zach Klaassen. I'm a urologic oncologist at the Georgia Cancer Center in Augusta, Georgia. I'm pleased to be joined today for a UroToday discussion with three folks from Mayo Clinic, Arizona: Dr. Mark Tyson, Aimee Boden, and Meghann Davis. We're going to discuss today the logistical considerations of starting an Adstiladrin program. So thank you all for joining us; we really appreciate it.

Mark Tyson: Yeah, thank you, Zach. We're delighted to be here.

Zach Klaassen: Awesome. Let's just start off at the top. Mark, please refresh our listeners on the patient inclusion criteria and some of the highlights of the results from the pivotal trial that led to the approval of Adstiladrin.

Mark Tyson: Yeah, the pivotal phase III, published by Steve Boorjian and colleagues, evaluated nadofaragene in the context of BCG-unresponsive non-muscle invasive bladder cancer. So, patients had to meet that classic BCG-unresponsive definition that was put forth by the FDA in 2018. Just by way of brief review, you could have a stage progression of T1 after a single induction course or a recurrence of CIS within 12 months of 5 + 2, or persistent or recurrent papillary disease within 6 months of 5 + 2. In that trial, they showed 53.4% of the 103 subjects with CIS had a complete response at 3 months, and that was maintained in 45.5% of them at 12 months. Some recent data suggested that about 10-11% had a complete response at 57 months. So, for a subset of patients, this is really quite effective. The median durability of complete response in that trial was about 9 to 10 months, and again, this was a large open-label, single-arm, phase III study. And so, based upon those data, the FDA licensed the product, and we're now using it commercially.

Zach Klaassen: Outstanding. Maybe I'll direct this question to Meghann and Aimee. How long have you guys been giving Adstiladrin at Mayo Clinic, Arizona, and roughly how many patients have you guys treated so far?

Meghann Davis: We started our first patient in late November of 2023, and I believe we're up to about 20 patients that we are currently treating.

Zach Klaassen: That's great. Fantastic. Mark, is there anything in terms of logistics and timing that you can share with our listeners in terms of when you decide in the clinic that you're going to treat the patient with Adstiladrin and how does that process work to where they're actually getting the treatment?

Mark Tyson: The very first thing I talk to patients about is the trial data that we just reviewed, how effective it was, what the side effects were. We didn't really discuss that, but we talk about side effects, we talk about efficacy, and then we also talk about logistics. It's an intravesical instillation once every 90 days. For people who are traveling, that's quite convenient. For anybody, that's actually quite convenient, but especially for those who are traveling. One sort of rub, and Meghann and Aimee will dig into this a little bit later, but I, ahead of time, as a provider, remind patients this is a very expensive drug, we have to buy it and then thaw it, and so we actually ensure that the patients are logistically on campus before we begin to thaw the medication.

Zach Klaassen: Outstanding. Meghann and Aimee, any practical learning points you can share with the listeners regarding, since starting the program, how does this maybe differ from maybe giving BCG or gemcitabine, docetaxel, or other intravesical therapies from your guys' standpoint?

Aimee Boden: Yes, it's become a very collaborative environment with operations and pharmacy. When we first started the instillations of these, we came up with a game plan which involved all aspects and we found that with some of the patients over time that it was quite painful and we originally started with no medication and then we went to Valium, 5 milligrams, and then subsequently we just changed to 10 milligrams of a rectal suppository. And this really helps alleviate some of the pain with the patients.

During the process as well, we utilize an operating room bed which has more functionality for the patient. It allows us to put the patient in reverse Trendelenburg, taking off some of the pressure off the bladder that the patient often feels, as well as tilting them side to side in order to maintain that medication in their bladder. Whereas with other medications like BCG, we don't need to go to such extensive measures. As well, the education involved with the patient, Dr. Tyson obviously informs the patient what's going on, but just because of the nervousness of the patient, sometimes we've found that if the RN calls the patient a day ahead of time and goes over everything and any other further questions that they may have, this helps alleviate a lot of their fears and questions involved with the process.

Mark Tyson: Yeah, Zach, and I just want to reiterate, we see patients who have tolerability issues with BCG and gemcitabine, obviously, we've all seen that, but it does seem like for this particular drug Valium is needed for more patients than not. We kind of progressed through this notion that we didn't need any to just using 5 milligrams orally to finally just settling on giving everybody, or recommending everybody have, a rectal suppository of 10 milligrams and that really does seem to allow them to be able to hold it better and to be more comfortable during the actual instillation.

Zach Klaassen: No, those are great points. I'm going to have two follow-up quick questions for Aimee and Meghann. Mark mentioned that you don't thaw the medication until the patient's on campus. The first question is how long from when the door opens until when they go home is the patient in your facility? Also, when interacting with the patients, how are they appreciating it or in terms of the 90-day not having to come every six weeks for induction for BCG? What's your feedback from the patient level when you're seeing them for that in terms of the 90-day perspective?

Aimee Boden: Well, they're very grateful for the treatment, very appreciative. Like I said before, it can be kind of painful.

Zach Klaassen: Sure.

Aimee Boden: That's some of the feedback I've got. The nurses are just outstanding. They stay with the patient during the whole instillation and then we have them stay with them for another hour and take their vital signs and make sure they're okay.

Mark Tyson: With respect to the time that we make them wait, we actually have them arrive at 8:00 A.M. for a 1:00 P.M. instillation. It doesn't usually take a full 5 hours to thaw the medication, I think we've done it in about 3.5, but it's just, God forbid, a plane is late, a flat tire on the way, an Uber driver is not sure where to go, they go to the wrong campus. There are just all sorts of things that could happen. We don't want to flush however many thousands of dollars it is down the toilet. So we definitely make them come on campus then to thaw it. I'm not sure that all practices do that. That's just a workflow that we've implemented.

Meghann Davis: The workflow has been very robust, Zach, as far as, Aimee alluded to it a little bit, from the ordering perspective to working with pharmacy for our revenue team, tracking and making sure that we're getting reimbursed for the medication. It does require a very specific and robust process to make sure that we are ordering correctly. Because of the cost of the medication, our pharmacy isn't able to store it here, so we don't order it until about a week before the patient is seen. And then there's a very specific process on when the medication is thawed and then once it's drawn and how long it's good for. So it just takes a lot of close communication between pharmacy and nursing and operations from day one. So I think we've got it pretty streamlined at this point, and there's been a lot of positive, I think, feedback from both the patients and the practice with that.

Zach Klaassen: That's great. Actually, a good follow-up question to that is, did you have folks on staff from the company for the first instillation or two, or how did that sort of work in terms of making sure you guys were comfortable?

Aimee Boden: Yes, we did. Dr. Tyson coordinated the company to come out and perform education for our nursing staff, and we walked through all the logistics of the medication, the side effects, all the education required, and then they were on site for our first instillation back in November.

Zach Klaassen: Excellent, excellent. Mark, in terms of setting up the program and challenges and maybe learning points, can you share with the listeners, from your perspective, obviously you're running a bunch of clinical trials at your site as well, what were the easy parts or what were the challenging parts for actually setting this up, maybe in terms of coverage as well, for getting these patients' treatment?

Mark Tyson: Well, I think once it became FDA approved and commercially available, we were all kind of looking forward to using it. Obviously, it's a good option for patients. It helps delay cystectomy for many people and leads to a durable complete response in some, so we wanted to make sure we had this option as soon as we possibly could. We coordinated with the company; they're outstanding to work with, very professional, and very timely in their communication, and they've been very accommodating.

There have been times when our pharmacist and their pharmacist had to correspond on certain shipping delays and those kinds of things, and I have to say that they've been great to work with in that regard. The main headaches, in the early days, were coding and coverage. "Is this going to get paid for?" I think everybody was nervous about that in the fall and heading into January. Now I think some of those questions are settled, and I think patients are tolerating it well. It seems to be working in the patients we've treated, a very small number, but we're happy overall. But I'd say those are the main pain points.

Zach Klaassen: Outstanding. It's been a great discussion. I just want to give each of you a moment or two to maybe highlight a couple of take-home messages for our listeners and for folks that are really starting to think about launching this at their cancer centers.

Aimee Boden: From a nursing perspective, I would say that it's definitely a collaborative effort between operations, the physicians, and the nursing team, with the patient at the center of that, and just to be able to allow the time and the process to unfold on what's best for the patient really made this successful.

Meghann Davis: Yeah, I would just echo what Aimee said and piggyback on that, the fact that you just have to really know what your resources are at your establishment and make sure you're partnering with all the key players, everybody from prior authorization, revenue, pharmacy, nursing, and operations, to understand exactly how you can operationalize the process and make it a smooth experience for everybody.

Zach Klaassen: Excellent.

Mark Tyson: From my perspective as a provider, I would just remind providers that when they talk to patients about the drug, they should keep in mind that failure is still more likely than success. It's 24% at a year, and so be thinking about plan B and plan C. If they're in that 1 in 4, that's fantastic and good for the patients, but we still need to be projecting down the road a little bit about what the next steps might be.

The other thing that I would remind providers is to make sure to talk about the bladder spasms during instillation. It really does seem to be kind of just during instillation and immediately after, and to highly consider using that Valium suppository.

And then lastly, I'd encourage practices to implement a workflow where patients are showing up on campus a few hours ahead of time, to make sure that they're there so that you're not losing doses. I know that I think the company has an insurance program for missed flights and flat tires and those kinds of things. We've never ventured to use it. So, reminding patients of that wait time and to bring a book is also helpful for patient satisfaction.

Meghann Davis: Zach, I think, too, just another piece to add to that is the vendor does have assistance programs to help with commercial patients that might need any out-of-pocket expense. We're fortunate enough here at Mayo that our revenue team has been able to partner with the vendor to be able to help our commercial patients with the out-of-pocket costs as well.

Zach Klaassen: Outstanding. No, it's been great. Another option in this disease space is great, and I think your guys' practical points are going to be really helpful for our listeners. So, thank you all again for your time and your expertise.

Mark Tyson: Yeah, thanks for having us, Zach. We're delighted to be here.

Zach Klaassen: Thank you.