It's going to get a 15-minute whirlwind tour of market access of hepatitis C drugs. I'm a writer for Genotype 2 and 3 with UpToDate. So the reason I'm really excited about talking about this is because some things went really well since late 2013 when we first had our all-oral combination therapies for hepatitis C. But we made some mistakes. And what worries me is that we have a very high risk of making the same mistakes again with the rollout of novel hepatitis B therapies, hopefully at some point in our near future. And we actually need to start thinking today about how to not make those mistakes for hepatitis B as we also try to still address some of the challenges and problems with hepatitis C. So I'm actually going to spend some time with this map right here. What I did was color-code the globe relative to access to one specific direct-acting antiviral, so Fosbivir, as a model for different trends that we're seeing in market access to hepatitis C drugs. I'm going to start with the purple countries. The purple countries were designated by Gilead as being allowed to have access to generic medications that were manufactured by generic companies, mostly in India, under voluntary licenses. When we talk about these purple countries, the first question is, do all of these countries actually have access to hepatitis C drugs? And the answer is no. And some of your previous speakers gave us a sense of why this is actually true. And I think a really important comparison that Dr. Thomas already has shared with you is why all of these countries, especially in sub-Saharan Africa, do have registered HIV generic therapies and now have over 16 million people on treatment. And it was because of Global Fund. It was because of PEPFAR. It was because of the virtuous cycle that you get when you can guarantee a generics company a certain amount of profit from volume of sales, and then that brings in diagnostics, and that brings in expanded care capacity, and all of the other stuff you need to then expand treatment. We don't have that in hepatitis C, and I think it's probably one of the most important challenges for us and our creativity to try to figure out, instead of waiting for Global Fund to take these on, which I think is the obvious solution, are there things that we can do today to start that virtuous cycle? One of the countries that you've already heard is Egypt, and I think of it as like the Nike Just Do It model of hepatitis C care. They really, I think, have shown many of us in green countries that we probably were over-testing and over-monitoring people. And one thing that I've learned in working in low- and middle-income countries is I learned a lot about my practice and how to improve my practice from seeing what's possible in countries that are forced to figure this out, because every penny counts when you're trying to expand care. I had the honor of working with Dr. Hamid from Aga Khan in Pakistan on a test-and-treat program, and I found, to my amazement, that the cost of the antiretroviral drugs were remarkably close to that of Andrew Hill and his landmark paper that described estimated manufacturing costs for direct-acting antivirals. We're hitting about that with a modest level of profit for the generics companies that are making those drugs. The diagnostics cost twice as much as the direct-acting antivirals. So for those of us in green countries where our diagnostics are really a trivial cost relative to the amount that we're paying for the direct-acting antivirals, we can't lose sight that in many areas of the world, the cost of the diagnostics are going to be a huge barrier, and we still need efforts, as you heard from one of our speakers, to develop affordable point-of-care testing, and I will say the Cepheid gets close, but finding that up-front $17,000 per analyzer is a real challenge. The orange countries are countries that decided to reject some elements of the Cefospovir patent. So in China, the patents were covering until about 2024, but then they rejected certain of those elements, and at this point, they have access to generics starting, I think, this year. I'm expecting probably in the next year we'll see generics being produced in China. And the other orange countries have taken some variation of patent challenges. IMAC is the non-profit to really watch in terms of very careful analysis of patent basis in various countries. The yellow countries are middle-income countries, for the most part, that are proximal to very wealthy countries and where there's a risk of parallel import. So for us in the United States, many of my relatives are in Texas, if you had complete open access to direct-acting antivirals at a price that would be affordable to the majority of Mexico, there's the high risk that people would start running across the border. We actually do cross that border to buy affordable medications. And then I'm going to pick on Hungary because I spent a couple of weeks there recently. If you had complete open access to direct-acting antivirals that are truly affordable in Hungary, they could be repackaged and sold in, say, Germany because of the open borders. I'm going to now turn to the United States. It's the market that I understand the best, and I'm going to tell you a little vignette about Massachusetts because it's the state I live in and you all are here in Massachusetts right now. So one of the areas I practice in is Beth Israel Deaconess. It's about a mile from here. And back in early 2014, we had about 2,000 patients with hepatitis C that were waiting for our antivirals. And as far as I can tell, it took us about 16 months to treat all of those patients. We started a baby boomer testing program back in early 2013. We diagnosed hundreds and hundreds, thousands of patients. At this point, we are identifying about 30 to 50 people a month. We have easy capacity to get all those people into treatment. I'm helping out a federally qualified community health center in Lynn, Massachusetts. They had 1,500 people that had been diagnosed. They only had two treaters, and they had only treated about 15% of their patients. They did a training program to expand treatment in the primary care pods, and I was helping out with that. So maybe now they have over 20% of those patients that are treated. And then I'm director of a needle exchange program in Framingham, Massachusetts, which is about 20 miles west of here. And there, nobody with hepatitis C has been treated. And just like you heard from Dr. Taylor, we're trying to figure out how to bring care to the people in a non-medical setting. And there's a lot of challenges with reimbursement. This is in a state that's 98% insured. So when we, within 20 miles of where you sit right now, can go from 100% treated to 0% treated, insurance isn't just our only barrier. But it is still a barrier for many, many people, the access to reimbursement. So the yellow dots there represent tribal nations. We have about 600 tribal nations in the United States. And the amount spent per person in our indigenous communities is about 25% of what we are spending in average in the rest of the United States. So in many ways, these tribal nations are like middle-income countries trapped in the country that has the highest drug prices in the world. So when you're advocating in your state, if you have people who receive care through Indian Health Services or Indian National Health Care, please remember to advocate them as you're advocating more broadly. Jails and prisons also have unique ways that they pay for drugs and are completely underfunded in terms of their health care. We have terrible access to treatment there. And I want to highlight the state of Louisiana that developed what's called the Netflix model of care, where they pay a lump sum, and then they get as much treatment as they can use during that time interval. This is a brilliant solution to a public health crisis. Because the more people they treat, the better they've used their money. And so you can imagine a system where now there's a real incentive to screen people, to figure out how to link them to care, to figure out unique mechanisms of care. And I know Washington state has recently announced a similar agreement with a different drug company, and I think this is one particular solution, especially in the United States, to approach. Many of you know that I spent several years with a public benefits corporation called TREC Therapeutics. And our goal there was try to develop an affordable regimen for these pockets that I'm talking about that still have very poor access. The method that we were going to use is take advantage of what's drug on shelf. Lots of pharmaceutical companies have a backup compound they decide not to develop, or they just shifted their line of business and they have meds that they're not using that are potentially available for in-licing. And that was our strategy. I'm going to show you a regimen without saying anything about its relationship to TREC, but this exemplifies what I'm talking about. Stephan Zoysen presented phase 2B data showing that the combination of AL-335, Odalisvir, and Simaprovir had a 99% cure rate at six weeks. Now, there's another drug on shelf, GSK-175. It's a very potent pan-genotypic non-nuke polymerase inhibitor that, obviously from GSK, that actually also has really good genotype 3 activity, which was one hole in the three drug regimen. Two, I think that this is a regimen that could actually treat a good number of people for four weeks, and we otherwise have no regimen that could do that. To develop this regimen would cost about $200 million, and about $100 million of that is the formulation, the manufacturing for clinical trials, and the manufacturing for commercial supply. That's a lot of money. That's a lot more money than most public benefit corporations have, but to put that amount of money into context, in one state, Massachusetts, in one year, 2015, in one payer, Medicaid, they spent over $300 million. But investors are who pays for drug development all over the world, with a few exceptions. And they want big returns. They don't want affordable drug returns. And this is going to be a challenge all of us have as we think about how to have access to affordable regimens within our current system. And I will tell you, it breaks my heart that that regimen will never be developed and will never be available for our patients. OK, so what were some of the challenges in hepatitis C that I think are still ongoing? We let payers drive how direct acting antivirals and the value to patients was defined. And I don't think we recognized initially that when they started talking about this $1,000 a pill, which I will say is one of the worst pricing mistakes ever made, how damaging that would be in terms of setting up a narrative, these people don't deserve this care. So we lost that narrative. We need to pick it up, because I think people have lost a lot of interest in hepatitis C. And we can't let people lose that attention. In 2014, there was one regimen I know I preferred to another regimen. But we accepted that whatever regimen would be reimbursed, we would use, unless there was a safety concern. Obviously, that trumps everything. And that allowed for competition. The amount of price lowering that we saw here in the United States in a very short period of time was unprecedented among branded drugs in the pharmaceutical industry. Competition works. The bills that we have up in front of us in the legislation right now around drug pricing will not work. And so we have to think about how to allow competition. As I've mentioned, we need to continue to advocate for especially publicly funded health care that is still really not able to treat the number of people they need to. A pet peeve of mine that's too complicated to get in here is best price. Our state prisons and jails are under the best price, which calculates prices for Medicaid. That's a real problem. I think, as I said before, we need some creativity about how to generate that virtuous cycle for access to DAAs in countries that don't even have them registered right now. What are some lessons for hepatitis B? First of all, we need to start right now figuring out efficient ways to screen all of the people undiagnosed with hepatitis B. It's going to be more complicated than just rolling out a baby boomer testing program. But I started working with baby boomer testing programs 10 years ago. There are still hospitals that don't do baby boomer testing. This takes a long time. We need to start now. We need to not silo. Right now, we have vaccine programs separate from programs to find chronic hepatitis B. They all need to be integrated. My personal belief is if you're alive, you can be characterized in terms of your hepatitis B status. And we also need to simplify the treatment algorithms. They are a barrier to care. We need to start expanding the primary care pool of people comfortable with treating hepatitis B now. You've heard several talks. We're scrambling to try to expand that provider pool in hepatitis C now. Let's not make the same mistake with hepatitis B. Payers, I don't even know why this is, but they got blindsided by hepatitis C. Part of it is they set budgets 18 months in advance. Once we start seeing phase 2B data and we start seeing how these hepatitis B drugs are going to be used, we need to go to our payers in our states and talk to them about how we see this being used in their communities. And finally, do not provide a roadmap for rationing in hepatitis B guidelines like we did with our early hepatitis C guidelines. That's it. Thank you. Thank you. All right, thank you for an outstanding summary about this incredibly important issue. We can open this up for questions at this time. So if you come to the central aisle microphones. To start us off, Dr. Graham, obviously this has been an ongoing evolution over the last several years with drug access. One of the topics you covered was the prison system. And so the question is, what do you anticipate will be the key steps necessary to begin penetrating both states and federal prisons to increase drug access? Recognizing that most states are just struggling with their fiscal issues already. In that context, how we make a dent for hep C? OK, now I'm going to do a pitch for best price. So here's the problem. All commercial payers have to submit the prices that they pay because the government doesn't want Medicaid paying a lot more than, say, our Blue Cross Blue Shields or other commercial payers. For reasons that I truly think we're in oversight and a mistake, our state prisons and jails are part of that pool of prices that are paid. So no state prison or jail is going to have a price lower than what we're paying on the commercial side. Because otherwise, it would lower the prices of all 50 state Medicades. So if you have a little bit of time, call your legislator and say, remove state prisons and jails from Medicaid best price. And they're going to say, what are you talking about? Because I actually had to argue with national Medicaid people to say that this was a problem. But I think it's a legislative solution that's going to solve a lot of problems, not just for hepatitis C, for hepatitis B, and for lots of other medications. I think we need to really see how the Louisiana model works. I think that's a brilliant approach. And that's specifically covering their jails and their Medicaid, their publicly funded programs. I'm actually a consultant for a lawsuit in Massachusetts right now for lack of access to hepatitis C treatment in Massachusetts. There's no easy, easy answer. But I think we have a lot more potential solutions now than we did, say, three or four years ago. Question in the back. Hi, thanks, Dr. Graham, for covering this information so eloquently. I think it can be really confusing for those of us that don't have the same background that you did. And just a plug for the audience, if you're interested in learning more about current hepatitis C treatment restrictions, we have a panel on Monday at 1.30 that will give an overview of updated treatment restrictions in Medicaid throughout the country in the Sheraton. So Dr. Graham, do you have any concerns with the Louisiana model, with the Washington model, with physicians being pigeonholed into one treatment? We're hearing from several who feel like the PA process already kind of takes control over what they can and cannot prescribe. What are your thoughts about how we can balance driving down prices and using competition while still giving clinicians the ability to choose the right treatment for their patient? Yeah, this is really tough. Back in 2014, 2015, the first question I would ask a patient is, what's your insurance? Not how old are you, how are you doing? And I never had to do that before. I'd never seen rationing like we experienced in the early rollout of direct acting antivirals. And I think we all finally accepted that unless we had a really strong safety concern that we could do harm with a particular regimen for a particular patient, that we would just accept that whatever it was that that person's insurance company covered, we would use it to the best of our ability and most of our patients got cured. Almost everybody at Beth Israel Deaconess is cured. And so you have to distinguish, I like this better from I have a significant safety concern. And I would hope that if somebody, let's say in Louisiana, had severe kidney disease and it wasn't safe for them to take the regimens that are being supported, that there would be an exception process. And that's true with any payer that has a preferred drug. And so this is one where nobody was getting treated. And so do you have a limit on your physician choice and now lots of people get treated? How do you balance that? I think it's something that we tend to be a little bit uncomfortable with, taking sort of the price of drugs into account. It's something that we've been trained not to really take into account, especially in the United States. I think other countries have shown models of this is how you treat as many people as possible. And we need to have more flexibility because I think that's gonna be the solution. And what we had before was horrible. And so I think this is better than that, nobody getting treated. One question regarding the penetration of generics here in the US, the first entry earlier this year. To what degree is that gonna have an impact on improving drug access here? How do you see that evolving over the next several years? Yeah, so when TREC was trying to develop this affordable drug, a lot of the investors would say, well, aren't we gonna have generics here in this country? And we were like, yeah, you're gonna have generics and they're gonna come out at about $20,000. The generics actually came out at $24,000. And there were a couple of reasons why we knew that this was gonna happen. One was the spread, especially for Gilead, of the list price versus the actual price people were paying after discounts and rebates was so huge that it was distorting that sort of pay ladder that we have in the very complicated payer structure of the United States. And then the other thing is, when you're relying on, say, rebates, you get them later, but you have to put out that full amount of money up front. And that was also causing some distortion because there were other regimens that didn't require that. And so that's why they put out the generics. They didn't do it because, oh gosh, now we need more affordable drugs. It was because that's actually the price that the regimens actually are right now. And so I don't actually think it's gonna change very much. The automatic rebate you get on generics for Medicaid is different than branded. And 340B handles generics differently than branded. And so you're gonna have some maneuvering, and if you're not sure about how this works in your health system, talk to your pharmacy director and the folks in finance to understand. We basically just write the generic name, and if it's more advantageous for a particular payer to use the branded, they use the branded. If it's the generic, the generic. I reassure people, it's absolutely the same. So don't not use it, but don't assume that you can predict the financial advantage of one of those options because for a particular payer, the other option may be beneficial. You're not gonna know because these negotiations are confidential. All right, thanks very much, Cami. That brings us to the end of the session. I wanna thank all the speakers and the moderators for a wonderful session. Please look out for the rest of the programming around hep C elimination at the meeting, and enjoy the meeting.

hepatitis C drugs

market access

global disparities

drug pricing

healthcare system

generic drug penetration