Ashish Kamat: Hello, everybody, and welcome to UroToday's Bladder Cancer Center of Excellence. I'm Ashish Kamat, Urologic Oncologist in Houston, Texas, and it's a pleasure to welcome to the forum, an expert, a friend, a bladder cancer addict, so to speak, Dr. Parminder Singh, who's joining us from Mayo Clinic, Arizona. Parminder, welcome to the forum and thank you for taking the time.

You were part of a panel that you put together and led at BCAN, the think tank that concluded recently that addressed a very, very important topic for our field and especially for our patients, the financial implications and toxicity and burden of bladder cancer. So really excited to see what you have to say in a summary of the session. I'm really excited, so take it away.

Parminder Singh: Thank you, Ashish. Thank you. It's always an honor and a pleasure to meet you. Be part of a session where you're presenting or you're part of intending and learn from you and always, always a fun meeting to attend. BCAN is very learning, very informative meeting, bringing great minds together and moving the field forward for bladder cancer. So this was one session, which was on the last day, the Friday of BCAN meeting, which was put together by myself and Matt Mossanen and Ruchika Talwar from Vanderbilt.

Matt is at Dana-Farber. And the idea was to understand how the cost of the newer therapies for bladder cancer is going to impact future work in this space, both research and clinical care and how the systems are gearing towards absorbing that cost, which comes with treatment and taking care of our patients. So essentially high-cost therapies, and then there is going to come up as complex combination of these regimens. This will lead to a financial burden in the healthcare systems which are already reaching critical levels, which we all are aware of.

So how is policy looking at this? How are sponsors, pharmaceutical companies looking at this and how we as physicians are looking at this space? What I've done is I have compiled the slides which were presented by all the speakers, and I'm going to summarize them and also talk about some of the important questions which came during the session as I speak through these slides. And then we can go for some question, answers in the end. And so with this first slide, Matt wanted to show the cost of the, from the lower risk to the high risk for non-muscle invasive bladder cancer, how the cost of care has gone up.

This was a study done by him and looking at 2018 in US dollars. And you see there that for a low-risk non-muscle invasive bladder cancer, the average cost is close to $50,000. But that goes to close to over three and a half, a hundred thousand dollars so high for high-risk disease and bladder cancer becoming one of the most expensive cancer to take care of in US by these numbers. And so what is this cost? So first thing is to understand where this cost is coming from. And so there is a direct cost, which is the medicines itself, and then there is an indirect cost which comes along by going through this treatment.

When somebody is diagnosed with this cancer, there is a cost on the mind, the anxiety, which comes with the diagnosis. There is a stress, there's missed work, there's impact on caregivers, there's changes in lifestyles. You have to visit physicians, go through different procedures. It does impact your quality of life. And then added to financial toxicities, which not only come by directly paying the insurers but also come in as paying the co-pays. And so when we look at the development in bladder cancer space for newer drugs, we see that there was a big gap for after BCG till Valrubicin came along. But then that was not very well taken up by the urology community as it was not very effective.

But then certainly now we have plethora of options coming up in 2020s, which are very expensive and very exciting new drugs in this space. And so not only these drugs by themselves, but then we anticipate in coming years there will be combinations of these complex new therapies which would then add to the incremental cost of giving these medicines to our patient and then taking care of them for any toxicities which come along. And so this slide wanted to highlight the, not just the cost of the drug itself, but also the visits that come along with it. So when we saw BCG, there was an induction phase and there was a maintenance phase.

But then these newer therapies, as you see the arrows, the number of the arrows going up. So those are the number of visits that the patients have to come in for their care and that adds to the burden of the treatment. And if we look at the overall cost, if you look at BCG and we see the median number of doses around seven, the cost is close to $1,100. If you go through the full treatment, could be close to $5,000 versus the newer drugs like Creptoestimagine, which is anticipated to cost somewhere close to a million and a half for full treatments.

And so clearly a big burden on the system is anticipated as these newer drugs are coming along. And this similar paradigm shift is happening in the advanced disease setting where we saw we had a big gap from platinum-based combination therapies. And then suddenly after 2016 immunotherapies and newer targeted agents like Erdafitinib and then antibody drug conjugates came along. And now the combination of antibody drug conjugates and immunotherapy, which are going to change how we treat advanced disease. These patients are responding very well and they're living longer and they'll be on these treatments for a longer time.

And so we see that with improvement of survival with incremental approval of these newer drugs as shown by these clinical trials where the immunotherapy changed the game for advanced disease. And now the EV Pembro has completely upended how we treat our patients coming into our clinics. And also important aspect to these newer drugs is that these patients are staying in response, which is CR or PR for longer time. Here, median duration of response for EV Pembro is close to 24 months. And we anticipate when these patients progress, either they continue on these therapies or they take a treatment breaks and they come back on these treatments.

Overall adding cost to the system. The same thing, these patients are staying in CRs. These drugs are achieving CRs, so then patients may want to stay on immunotherapy longer in thinking that this will help them maintain their CRs and then adding cost to the system. So if you look at the numbers in this, if you look at gemcitabine and carboplatin combination, estimated cost of four cycles is close to $1,200 versus sacituzumab govitecan, if we look at median of six cycles, close to half a million dollars. And EV Pembro, similarly, the cost will be very, very high.

And so then we had Michael Louie from UroGen talking about from the sponsor angle, how this cost comes about, where is this cost coming in when sponsors, they look at placing the price to the drug, which they have developed. And we were not, well, at least I was not aware of the non-clinical cost of development, which is close to 300 to 500 million dollars, which the sponsors look at when they take on a molecule from a non-clinical side into the early clinical phase of the development. And so then there are series of trials going from phase one, two, and three, and we know that most of the drugs will fail in early clinical development and only few drugs will move on to phase three, and very few would then get approved for their indications.

So this, all the incremental cost from non-clinical to phase three is added up with each molecule which is investigated, and then that adds burden to the sponsors. So the overall cost of running clinical trials and also drug development is added to the sponsors anticipated pricing of the drug. They also then may have to perform further testing in post-approval setting, which adds further cost after approval, which they have to kind of factor in when they're pricing their drug molecules. And so then we had Rich Toner from Mayo Clinic. We asked him about how large corporations. He's the director for reimbursements for drug reimbursement in Mayo Clinic, Mayo Clinic being a large corporation.

We had invited him to understand how large corporations are looking at covering the lives of the employees through their insurance plans and with the rising cost, how would that factor in. So he gave us a very nice overview of how hospital profits or how hospital margins work. And so this was something which was totally new for me and for a lot of the folks in the audience where he explained that in the first slide where you see the payer mix cross-subsidy commercial to the government, the black bar is the margin we receive from commercial insurance for providing a certain care for a certain diagnosis.

And the red bar, which is the negative bar, is for a similar coverage the hospital systems receive from the government payers. And then when you subtract both of them that the smaller black bar is the net margin is where the large hospital systems work and they cover the services that they provide. Similarly, if you look at the drug cross-subsidy, how the drug product margin works for physician service, versus physician services, if you see the first black bar is the drug product margin for any given drug which the hospital buys and administer to the patient.

And but at the same time seeing the patient in the office goes down in negatives because that doesn't bring any revenue or is enough. The revenue is not enough to accommodate the cost of care in the office. And so then the net margin is again, a very small margin where the hospital systems work and provide this care. To this point, Yerl Orton came up and he asked a very interesting question. And he mentioned that when we think about drug development cost and how sponsors should price, they should highlight that many of the or a lot of pre-clinical work is done by government grants, the R01 funding to various investigators throughout different institutions.

Federal funding is key in non-clinical development. And then as those drugs go into phase one and two, many sponsors will buy those molecules and take them to further development. But many of that pre-clinical work is done by federal government. And Michael alluded to and said, "Yes, but at the same time, there are so many molecules in non-clinical side or early clinical development, which doesn't make it to the final leg of the journey to the approval, and then they still contribute cost."

And so then I'm forgetting who asked on this, but there was an initial impression or understanding that when hospital systems, when they bill for a drug, there is a 10% margin to the drug which was received by the practice. And this was something very, very old. Rich and Stephanie Berg, who was from one of the largest payers in the DC area, she was there as part of the panel. They explained to us that this is not true anymore. With the rising cost of these drugs, that percentage margin is not there. So then physicians are not incentivized to use high cost drugs. There is a cap to that margin.

And so for example, if 10% of $1,000 is a hundred dollars, but if a drug is costing $10,000, then the margin is not 10%. It is a negotiated margin based on the relationship and the amount of volume of care provided by the physician or the office or the hospital with the payer. And that could be as close to $1,000 even for a $10,000 drug. And so then the higher margin drugs are actually not incentivized to be used for our care.

And that was again, very something new to hear for a lot of the people in the audience where they thought that many physicians feel incentivized using higher cost drug. We need to understand that these higher cost drug brings a lot of risk to the practices as if they're not reimbursed, then the physician practices may lose the whole money on it. Same thing, Rich continued to show us that, to give us an example for gene therapies in sickle cell. So where this balance get off, because most of the patients who receive these higher cost drug, for example, sickle cell population belongs to government payer, which is more Medicaid.

And so then the net margin also goes into negative. And that brings out a challenge for the large hospital systems to cover the cost of these drugs. And so there is a commercial payer for cell and gene therapy, but also out-patient drugs. And that's where newer programs like Mark Cuban Cost Plus Pharmacy are helping cover or reduce the cost of drug, which is something, a movement in the right direction was highlighted by a lot of speakers on the panel and also by the audience. And so then came, Ruchika came on and she does a lot of work in advocacy and cost of care in urology and urologic oncology.

And she highlighted how our national health expenditure is moving. We are looking at 4.8 trillion and projected will reach to 7.7 trillion by 2032. And who is paying for this? Is the large chunk is still paid by government health insurers is a green bar. Some of it is the out-of-pocket part and the rest is the private health insurers. But as this cost is going up, the system is going to get more and more stressed. And so there is need to improve this and improve efficiency.

So where is the efficiency coming in? And so the newer administration currently is looking at reductions in Medicaid. They want to cut back on Medicaid. So then they are trying to push more efficiencies into the system. They are overhauling public health and research agency to make them more efficient, reduce costs. And then on the day of the presentation, the Trump administration sent out a letter which was posted on the Truth Social that President Trump asking for pharmaceutical companies to reduce the cost of drug by 59%. And since then, we have seen a follow-up on that to the pharmaceutical companies to bring the price of the drugs to the favored nation cost to the U.S. consumers, and which could be one way to look at reducing cost.

But then how this will be translated into the practice is still to be seen because it is also very expensive to maintain and administer and then develop these drugs in the US. And so all this needs to be brought in and solved together. And some of the proposed bills which we are looking at to solve these problems are Cancer Drug Parity Act, Prescription Drug Affordability Act, and Improving Seniors' Timely Access to Cancer Care. And there is a continued need for advocacy to have predictable costs. We want to ensure there are transparency laws between different practices.

The cost of care could be different. We want to bring transparency. We also want to reduce out-of-pocket cost for our patients and particularly for normal cancer therapy where if we calculate the percentage of the drug cost, it can go very, very high. And so there was a lot of enthusiasm at the end of the session. There were so many questions that we couldn't even reach to the end of it, but the whole system, and especially Stephanie Berg who is one of the, part of the large coverage providers in the DC area, she highlighted that the system is geared towards helping patients and we as patients should not be worried.

There are system processes in place and payers have been covering even more expensive therapies, gene therapies, CAR T cellular therapies. Already there are processes in place and negotiations will continue to bring the latest and the most novel therapies to our patients. At the same time, the payers are working with the government to see how they can reduce costs, but they're not taking away the options from our patients in any way or form.

These drugs will be available for patients who clearly need them. And the payers are... Their intent is to cover the care and not just say no to our patients. And that was very reassuring to hear from her that how payers are looking at all this as a rising cost and how we as patients and providers should see them as partners and not just an antagonistic team against providing care to our patients. So with that, I'm going to pause and see if you have any questions, Ashish.

Ashish Kamat: Thank you, Parminder. You covered a lot of data and a lot of interesting Q&A that happened at the think tank. I have two points I want to sort of bring up and see what your perspective is. One, people who often cast aspersions such as was done, and I'm glad Stephanie clarified that yes, physicians are not going to prescribe the more expensive drug just because it's more expensive. Right? But I think some of that skepticism comes in because even today, as of right now, Medicare Part B does allow practices to have ASP plus 6%. And then of course with the sequestration that occurs, it's about 4.3% or so.

So clearly 4.3% of a million is a lot more than 4.3% of BCG, which is 150. And I think that's where the skepticism comes in. So just to clarify to people that are listening, we don't think that anybody that we know is doing this for the money, but the skepticism comes in there. I want to ask you one question. I grew up in India, did all my schooling there. I still go back. I try to help folks in India. I also through the International Bladder Cancer Group, and we just had our 20th meeting here in Houston recently.

And we are a global organization. Right? So points that are often raised are, yes, we're focusing on these drug costs, they're phenomenally expensive in the U.S. and say hypothetically it costs $300,000 to get a 90% cure fraction here. From a population standpoint, that may make sense in a rich country, but what about countries that can't afford that? What's your view, Parminder, as an individual? 90% efficacy for $300,000 as a population or 75% efficacy at a $100 for the entire population, how do we balance that when it comes to the global patients that we all want to affect?

Parminder Singh: This is a very valid point, Ashish and I raised the same question at the ASCO meeting when the data was presented, updated with Shilpa, that how are we envisioning the impact of this care in countries where the cost would be, it is not just feasible to have this kind of cost? And for now what has happened is that drug companies have used a term called "favored nations" where they will price the same drug at much, much less cost to that nation based on what the nation can afford.

And so the same cost would cost maybe a hundred thousand dollars in the US, but maybe $10,000 in India. And so this difference is what is being pushed at this point in current administration that we want more equitable costs all around, not just the high cost, but the cost which is something which is equitable. So reduce the cost in US, raise the cost in other countries in Europe and then try to balance it out across. US traditionally has taken a view of providing this view of getting these drugs to...

Especially from HIV we learned that many drugs were provided to Africa and Asian countries and same kind of thing is being said by the sponsors, that they're providing free drugs. And in my communications with the sponsors, I was asking how they are envisioning the impact of these changes and how will they provide care. And they said they'll highlight how they provide the drugs at a lower cost and are free to many patients here in US and also in other countries. But it is to be seen now with all the changing paradigm which is happening at the government level, how will this impact? But clearly I don't see this such high cost being manageable for any nation at the population level. If you think of India with 1.4 billion lives, how would that nation cover such an expensive drug?

Even if we have 10, 15 percent incidence of bladder cancer, then the number of patients who needs this kind of therapy is so high. Then there are biosimilars being developed in China and India, which I think with improvement of technology transfer, I think India and China will be upcoming with a new force and they probably will be able to catch up with the drug development and bring these newer therapies to our patients in those countries. And we have seen this in the integral drug conjugates, which are coming along from China in bladder cancer. And so we'll see how this plays out, but at this point, it's a mess because the cost is so high and patients who need are all over the world and it's impossible at this cost to cover all this.

Ashish Kamat: Yeah. No, it's disheartening in many ways, but it's almost, it's a plea and a call to action, not just from the governmental agencies, but from us and groups like ours. Parminder, thank you for taking the time. We could chat about this forever and ever, but we'll let you go. Always a pleasure and hope to engage you in some of the global efforts that we're doing through the world Bladder Cancer Patient Coalition, through UroToday and through IBCG as well. So always a pleasure. Thank you for taking the time.

Parminder Singh: Thank you so much for your invitation. Thank you.