In 2013, hepatitis C killed more people than the 60 other Centers for Disease Control and Prevention (CDC) reportable infectious diseases combined. In the United States, there’s an estimated 2.4 million cases of hepatitis C. The development of a prophylactic hepatitis C vaccine is critical—yet has eluded researchers. Despite this challenge in vaccine hepatitis C research, there’s hope that change is on the horizon with the appropriation of additional vaccine research funding.
To find out more about the hepatitis C vaccine landscape, Terri Wilder, M.S.W., spoke with Annette Gaudino and Suraj Madoori, M.P.H., M.S.J., M.A., of the Treatment Action Group (TAG). Annette Gaudino is TAG’s state and local policy director, where she works to advance hepatitis C, tuberculosis, and HIV elimination efforts in U.S. jurisdictions, with special attention to the needs and human rights of people who use drugs. She also contributes to TAG’s policy work on prescription drug pricing and health systems equity. Suraj Madoori is TAG’s U.S. and global health policy director, directing the organization’s policy and advocacy work across HIV, tuberculosis, and hepatitis C. Prior to joining TAG, Madoori was associate director of the HIV Prevention Justice Alliance and federal policy at the AIDS Foundation of Chicago.
TAG is an independent activist and community-based research and policy think tank fighting for better treatment, prevention, a vaccine, and a cure for HIV, tuberculosis, and hepatitis C.
Terri Wilder: Thanks to both of you for speaking with me today. So, Suraj, I wanted to start with you first. Recently, TAG’s appropriation work for hepatitis C vaccine research had a big win in the form of new funding for fiscal year 2020-21. And I’m wondering if you can tell me about how that happened.
Suraj Madoori: Thanks, Terri.
I think it's a really exciting development that points to the complexity and to the politics that appropriations advocacy usually involves, and how it really does take multiple partnerships across coalitions and across diseases to get some of these acts through.
We have a leadership position within the Federal AIDS Policy Partnership, the FAPP, and we specifically lead the HIV Research Work Group, along with AVAC. And so, Kevin Fisher [AVAC’s policy director] and I had been working on a lot of our asks for [fiscal year] 2020, around maybe February of last year, of which we strongly want also to include support for comorbidities associated with HIV. This is a little bit of a shift from how the HIV Research Group used to work, in that the HIV Research Working Group used to really focus acutely on increasing resources at NIAID [National Institute of Allergy and Infectious Diseases] and OAR [Office of AIDS Research] for HIV research.
But I think over the years, what we’re sort of getting more knowledge on and more depth on is the fact that a lot of HIV research dollars actually help support cross-disease research, such as TB [tuberculosis], for example, and HCV [hepatitis C]—and viral hepatitis in general. We started thinking more strategically about how do we ensure that not only does HIV receive a strong amount of research dollars—which it hasn’t had for a while—but how we also make sure that the comorbidities, the other diseases that likely kill people with HIV, or communities vulnerable to HIV, also receive the same kind of attention by appropriators and receive additional research money, as well.
One of the blessings, I’d say, about research money with appropriators is that it’s a very strongly bipartisan issue. And if you look at the last couple of fiscal cycles for, probably even since 2017—so, we’re talking about the first Trump budget—there have been subsequent increases to NIH [National Institutes of Health] for a long time now. We’ve seen $2 billion to $3 billion increases to NIH and NIAID for about three years—which I think is like a little bit unprecedented, but also demonstrates how much Congress values the NIH and the value of the money that goes into producing the next wave of treatments and vaccines and things like that for HIV or HCV—or any disease, for that matter.
And so, for us as advocates, I think we really saw the opportunity: If Congress is really interested in continuing to fund NIH—and especially now that we’re in a pandemic, it’s even more magnified—why not strategically hook multiple research asks onto this wave of funding that we’re seeing Congress currently allocate, given that NIH is a big darling for a lot of appropriators right now?
We started out really by, one, crafting our messaging around ensuring that any sort of increases that would apply to HIV would in some ways also apply to HCV and viral hepatitis. So, I think we had that going in our favor—that we were not just going into these offices as HIV advocates, but that we were really strongly advocating for other areas of research, which would have benefits for HIV.
And so, in doing so, we had a really strategic plan to basically divvy up the targets around Congress, based on membership of committees. And so, we, one, partnered with another FAPP work group, the AIDS Appropriation and Budget Coalition, and went into all those meetings representing research, and talking to appropriators about the need for research dollars, including HCV as a recipient that really needs the tools, such as vaccines, to receive additional funding.
And I think the other thing that we also did was, we scheduled a lot of our own targeted meetings around HIV research, and bringing together what we actually kind of call—it’s sort of like an ACT UP old guard of HIV activists who are so interested in HIV research, and capitalizing on their history in advocating for increased research funding to also help spread the word and these asks to Congress members as much as possible.
The other thing that is also really important to point out here, to the credit of other disease [advocacy groups] that I alluded to earlier, was that when Congress came through with their first budget proposal—so, first the House puts out theirs and then the Senate puts out theirs next—one of the things that we saw was that the hep B advocates were actually amazingly productive and effective in getting very specific language within the appropriations bills that targeted funding and attention towards hep C.
I think one reason for that is, I think that the hep B community is really heavily organized and has been working on this for a long time. And so, I think for us it was also a strategic opportunity to see the work that’s been done by some of our allies in hep B, and then kind of leverage that a little bit to say, why not include hep C as an equitable recipient of funding? Because there are some really stark needs, as we know, for hep C, as well, in terms of funding.
And so it was really interesting to go into those meetings, but not really get an indication one way or another from appropriators around what would be priority. But I think what was surprising to us was that when the final appropriations bills came out—and what was exciting for us is that we actually saw about a $25 million increase to NIAID for HIV research, which was actually one of the largest increases that we’ve had for a very long time for HIV research—but then under that was this $8 million increase for HCV, which was just as surprising.
And so I think all of these factors came together at the right time to eventually see an allocation appropriation of $8 million to HCV vaccine research at NIAID—which I think was a pretty big win, but also something that was both kind of unexpected but also just, you know, an under-radar win.
TW: Great. On March 18, the National Institute of Allergy and Infectious Disease, which is, of course, part of the National Institutes of Health, released a funding opportunity announcement, seeking applications for rational design of vaccines against hepatitis C. According to the announcement, the purpose of the funding opportunity announcement is to develop and assess novel candidate vaccines for their ability to induce protective immune responses, and to select promising candidates for preclinical development in appropriate animal models. The deadline to apply for this funding is coming up very quickly, June 15.
And so, I’m just curious. What are activists hoping will happen as a result of this funding announcement?
Annette Gaudino: Yes. I’m happy to discuss this more in detail. But I just want to say, broadly speaking, that we’re hoping that this funding is catalytic, that it is the start of a concerted effort that’s publicly funded and privately funded to get to a hepatitis C vaccine—a viable, effective hepatitis C vaccine.
And, frankly, without even this small investment, efforts would be stalled globally. And we can talk now a little bit more about why that is. But this is really a first-of-its-kind of investment, both in how targeted it is towards vaccine development and the size of the investment. So it was something that was sorely needed and is coming at a very opportune time, and really is rescuing the science around this, which had effectively been stalled as a result of some early trial results, and just the landscape of what’s happening with hepatitis C treatment.
TW: So, now, we have a vaccine for hepatitis B and hepatitis A. Why has a prophylactic hepatitis C vaccine eluded researchers?
AG: So, continuing on this train of thought: Basically, there are two distinct but related categories that the challenges fall into. One is resources, funding, as we were just talking about; and I’ll come back to that. But then, just the basic science of it.
So, to start off, we don’t have a good mouse model for hepatitis C. The animal model that we use is chimpanzees, who can get infected with hepatitis C. So that adds to the cost of basic science on treatments and prophylactics, vaccines for hepatitis C, and just sort of the complexity of doing those kinds of early basic research and basic science studies.
In addition to that, hepatitis C virus is very diverse. There are six subtypes, genotypes; and also a seventh type, that’s rare but does exist. And so, ideally, you would want any vaccine candidate to be effective across those diverse genotypes, those subtypes. And that can be extremely challenging.
In HIV, we have two main types: HIV-1 and HIV-2. And, obviously, HIV is not the same, and the involvement of the immune system complicates things even further. But we are many decades into the HIV pandemic, and we have not achieved a prophylactic vaccine for HIV. So there’s just some basic science that’s very, very challenging when it comes to developing and doing basic research for a hepatitis C vaccine.
And then, going further, on the resource side, I think in some ways we’re somewhat a victim of the success of hepatitis C treatment. Because early in your hepatitis C infection, chronic infection, it can be cured at rates of 95% or better—that sends a signal to the market that hepatitis C is over. The story is done. So, we don’t need to put any more investment into therapeutic and into prophylactic vaccines. There’s no there there. There’s no incentive.
So, the fact that this U.S. government and public funds are now being put into this effort is really, really important, because there’s just no way that I see that the market is going to deliver this essential public health tool. There has to be investment and care put into the public health response through public funding in order to deliver [for] people at risk of hepatitis C infection, and those who are living with and then ultimately cured of hepatitis C infection, to continue to protect them and others, and stop forward transmission.
TW: On May 29 of last year, 2019, the National Institute of Allergy and Infectious Diseases announced that an experimental vaccine was not found to be effective at preventing chronic hepatitis C virus infection in adults. And so, this was according to results from a clinical trial that was sponsored by NIAID. Can you tell me a little bit more about that trial and why it wasn’t effective?
AG: Sure. That was a multicenter trial. It included people at risk of hepatitis C infection. Specifically, people who are actively using and injecting drugs in California and Maryland; and then in later years, added a site, a recruitment site, in New Mexico. It eventually recruited about 275 patients in either arm—in the placebo arm and in the arm that was actually receiving the vaccine—and it was two injections. The goal was to study the efficacy of this vaccine in a high-risk population with ongoing risk of transmission, to prove its efficacy.
Unfortunately, what was found was that roughly the same number of patients, around 14 of patient participants in each arm, eventually did get infected with hepatitis C virus. And so there was no difference seen between the control arm and the therapeutic arm of the trial.
I’m not a virologist. I think those data are still being studied and reviewed. I don’t think anybody really knows why this particular vaccine was not effective in these patients. We know a vaccine is feasible because there is an immune response to hepatitis C virus infection. Some percentage of people who do become chronically infected do manage to clear the virus spontaneously. So, the immune system is responding to this; it just obviously needs a little bit more assistance. So, we want to be able to elicit an even more effective response so that you can prevent actual infection of liver cells, and you can stop forward transmission.
So, there’s ongoing work using other approaches to vaccine. There’s a group at Oxford that reported some preliminary studies, back in 2019. And when presenting their work at the International Liver Congress, they explicitly stated that they were having a really hard time finding commercial funders, private funders interested in taking their basic science forward, in taking their research forward. There’s just—the market didn’t see profit in hepatitis C vaccine. And their work was effectively stalled.
Also, as we’re learning through the COVID pandemic, you know, viruses can be really, really, tricky—very, very complex. And we might need a combined approach in order to develop an effective prophylactic vaccine against HCV—which would mean cooperation among potential competitors, commercial competitors, to bring their vaccines together into some sort of combo vaccine that would be more effective than either approach alone. You really, really need to have somebody mediating that process and making that a priority and moving that forward.
Commercial interests by nature are competitive. There’s no incentive for them to cooperate to bring a product directly to market together. They don’t want to share data. That’s just not how the commercial drug development process works. So that’s another reason why it’s really, really encouraging to have such a big investment by NIAID to kind of drive this forward and, as Suraj was saying, hopefully set the term under which this vaccine will be accessible to people.
TW: And so, when you’re referring to commercial, I’m assuming you’re referring to pharma. I had another hep C activist tell me that vaccines have not been seen as commercially viable by the pharmaceutical industry. And so it makes me think, why would PhRMA [Pharmaceutical Research and Manufacturers of America] not think it’s commercially viable?
AG: Most vaccines as a commodity aren’t, you know, expensive commodities. It’s not an $84,000 vaccine.
SM: Right.
AG: And so, you really have to sell millions of them, or deliver millions of this product, in order to reap multimillion or billion-dollar revenues from it. So, that’s the first thing, just looking at the bottom line.
The other thing is—again, going back to the point of how successful treatments have been and, sort of, the shrug of, Well, why do we even need them? We can just treat people with these great new drugs.
And, while it’s true that the prices of direct-acting antivirals have come down significantly over the years, due to some increased competition in the marketplace via new drugs that have been approved and proven effective, we’re still talking tens of thousands of dollars in the U.S. market and in other high-income countries. So, they’re still not cheap, by any stretch of the imagination. It’s hard to argue that they’re really affordable or priced appropriately.
So, there’s just a gap there between what drives and what incentivizes and what motivates pharma, which is bottom-line revenue, and the end product of this research, and who would get it, and how much it would actually—you know, should cost, in order for it to be widely accessible and, therefore, really do the job it’s designed to do—which is, end forward transmission and really help speed the elimination of hepatitis C, and end the pandemic.
SM: You know, just kind of as a little bit of a parallel—and I think Annette sort of hit the nail on the head—we can really learn from other diseases, as well, as to how far they’ve come in advancing a vaccine candidate.
So, for example, like TB, tuberculosis: We currently have a vaccine, a viable vaccine candidate, that’s showing a protective effect that is advancing into Phase III, but currently stalled by the private developer, despite a lot of spotlight and interest in seeing this vaccine move forward, because there’s just a need for it. So I think this is an important lesson—this would apply to HCV, as well. Because at this point from what we’re understanding, it’s that the company—and I imagine this for a large swath of companies that are thinking about this as a commercially viable and profitable product—don’t want to assume all the risk in the production, and eventually having to fund Phase III studies, and things like that—which do require a lot of resources.
And so, what we’re seeing is that often it takes a coalition of the willing, of funders to come together that see this vaccine could make a huge dent in ensuring that key populations are well protected from HCV. And so what I think is going to happen downstream is that, as a result of this funding, that we see a possible candidate, a vaccine candidate for HCV, advance to Phase III. We have to also be prepared as activists and advocates to ensure that it moves beyond Phase III, and that it is—it continues to receive government support. Because I think that what we’ll find is we’ll be stuck in that scenario, where there will be a commercial—a private company that’s advancing it, but that doesn’t want to assume all the risk in Phase III studies—and we would need some sort of coalition of the willing that would require multilateral institutions, private funders, as well as governments, to advance a vaccine candidate.
And so, we have to be prepared to ensure that there is a good pathway for any candidate from this $8 million that we see now, thinking ahead about ensuring that other stakeholders, all along the pipeline, are well primed and positioned to continue to help support potential candidates that come through this initial investment. So I think that’s just something that we need to really be forward thinking about, and making sure that the advocacy around getting this initial investment through U.S. appropriations is seen all the way and walked through to an actual vaccine for people who are currently vulnerable to HCV.
AG: The core part of any business plan is, who are your customers? Who is going to purchase your product? So, looking even beyond the initial investment, who is going to be buying vaccines for the people who need them?
If you look historically at when Medicare coverage moved to include adult vaccines—for example, for hepatitis B and for flu—you saw, in both cases, a two-and-a-half to threefold increase, in the number of clinical trials for vaccines for those infectious diseases, for hepatitis B and for flu, when Medicare extended that coverage. As soon as commercial pharmaceutical companies saw that there were going to be purchasers at the end of their drug development pipeline, they got in the game. And so that’s the other aspect of this—who are your customers? Who are your purchasers? And in a global climate, where especially people living with hepatitis C in low- and middle-income countries are seeing very limited access to curative treatments because their governments are not investing in treating them, thinking about how you would get government payers, public payers, to cover and to pay for vaccine can seem like a really far off target or a secondary priority.
That’s one of the reasons why TAG actually was following this research. Because we both have the science expertise to follow it, and to push it; but also because it can’t be a priority for some of the other partners and other folks in the hep C space who are trying to advance things on the country level, or on the state level, in the U.S. case, who are really focused on just getting people treated.
So, we understand that this is looking way upstream and way forward, with regards to the science, and more investment needs to be made. But that’s kind of why we were in there, trying to push for this.
TW: Who do you think will benefit the most from a hepatitis C vaccine?
AG: It’s basically the people who are at risk and who have a disproportionate burden of hepatitis C disease right now—which is, specifically, people who use drugs and men who have sex with men.
Now, we’ve seen in both cases actually very low rates of reinfection after cure. A little bit higher rates of reinfection among men who have sex with men, although it’s a smaller proportion of the total community that is infected with hepatitis C or has chronic hepatitis C infection. But we’re not going to be able to test and treat our way out of these pandemics in both those communities without something that’s really, really effective prevention.
And, unfortunately, people can still struggle to access harm reduction services and other supports that they need in order to really prevent ongoing transmission.
One approach would be a test, cure, and vaccinate approach, where everybody who received the hepatitis C treatment would then also get vaccinated to prevent reinfection. Right? That’s something that you could potentially bundle in procurement with your meds, you know? Again, but that would take coordination and partnership. You would really need somebody kind of knocking heads together to make sure you have that approach.
Obviously, of course, anybody who’s at risk, especially those two communities—the communities of people who use drugs and men who have sex with men—you want to give them a vaccine before they get infected, of course. So that’s the obvious thing to do.
And, also, it’s important to note that even a vaccine that’s not 100% effective or, you know, is closer to 70% effective or 60% effective—for example, you see sometimes the annual flu vaccine can vary in its effectiveness—would still be a huge advance for prevention. Because what you really want to do is you want to bring the viremia down in a community, or in a network of folks.
If you are vaccinating folks who come in contact with each other—sexual contact, or they use drugs together (hopefully they’re not sharing equipment, but it can happen)—and you bring down the prevalence of infection at the same time by doing coordinated vaccination; now, everybody’s risk is down. Everybody’s individual risk is now going down. And you really have a chance to stamp out the pandemic and the epidemic in that community. And that has a ripple effect.
So, even a vaccine that’s not 100% effective could really be a game changer.
TW: I just wanted to quickly ask about something else that TAG was involved in. On April 9 of this year, 2020, there were 76 organizations that signed and sent a letter to Speaker Pelosi and leaders McConnell, McCarthy, and Schumer, regarding support for vulnerable populations—specifically, people impacted by viral hepatitis and folks impacted by the overdose epidemics.
In the letter, it stated that these communities had needs that must be included in the fourth COVID-19 package. And I’m wondering if you could just quickly tell me about the purpose of the letter and how that kind of rolls into all the other things that we talked about today.
SM: As you have probably seen with the amount of activity in Congress, there’s been a lot of money flowing outside of regular appropriations with the stimulus bills—targeting funding to CDC and NIH and other entities to help support the COVID-19 response.
And with that, I think advocates view this as an opportunity to bring additional funding to programs that are impacted by the pandemic, which, what we’ve been tracking on the ground were a lot of HCV programs, for example—which I think Annette can speak to—is that COVID-19 is definitely drawing upon resources that are originally allocated towards hepatitis and towards TB or other diseases.
So, while all that expertise is being taken to obviously fight back this pandemic, we definitely need to support the continuing and strengthening of these programs, especially to weather a pandemic like this, to ensure that they are providing treatment and services to people who are most impacted by HCV and other diseases. And so, being on that letter is part of this effort of trying to capitalize on the stimulus funding that is flowing from Congress—although it was really disappointing to see, with this potential stimulus, still kind of being stuck in neutral.
The Democrats have put out a bill called the HEROES Act, which I think was a very laudable bill. But it was also just a $3 trillion messaging bill. And when you look at the text, you only really see any money for hepatitis within the context of opioids, when I really think we need to have dedicated line funding for all the centers across NCHHSTP [National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention] and CDC, versus this kind of thing where the only kind of hep C that’s going to get money is if it’s bundled with opioids.
And so I think there was a real disappointment, even with the Democrats’ bill, that there wasn’t a dedicated amount of funding for viral hepatitis within that big $3 trillion proposal. And it’s even less clear as to how any bills will advance at the Senate, for the most part, and kind of what McConnell has been indicating is that they’re kind of done funding anything that is related to a liberal wish list, and really want to narrowly cast the next bill around protecting corporations and businesses from liabilities for, you know, not protecting their workers—which, you know, is ridiculous.
So, anyways, I think the next stimulus package is going to be a really interesting fight. I think there’s still a lot of work to be done, not only with appropriators and with people in Congress, but with our own advocates—especially in the HIV space. I mean, we’ve been targeting for increases across all the centers, and ensuring that somebody who is still funded can help support programs that are getting closed down—and especially about hepatitis and HCV programs, which—Annette, if you want to go a little bit more into how they’re being impacted by it, by the pandemic?
AG: Absolutely. So, first I want to thank the National Viral Hepatitis Roundtable and the AIDS Institute, which are two national viral hepatitis advocacy organizations and networks, and all the members of Hepatitis Appropriations Partnership. NVHR and AIDS Institute led on the drafting of that letter, and all the partners signed on and really circulated it.
What we’re seeing on the local level, on the state and local level, is a complete freezing of direct services, especially to people experiencing homelessness and people using drugs. Community outreach workers, peer educators, navigators don’t have the PPE [personal protective equipment]; don’t have the resources to safely continue to screen people for viral hepatitis and bring them into care. Clinics were not seeing people and were shutting down. You simply can’t initiate care via telemedicine. It’s impossible.
So, if you weren’t already on treatment, you have not been able to get tested and access treatment for months now. And it’s going to continue in many cases—not just depending on social distancing measures that are in place in your local community, but just resources and failing needs of people. People are focused on getting food and just their day-to-day existence. They’re not really focused on trying to treat a chronic disease, which may not significantly impact their health for a couple of years. So, we’re going to see a huge step backwards, actually, with regards to hepatitis C, the hepatitis C epidemic and pandemic response.
When we’re looking at the next round of funding from the congressional side, we really have to ask: Where’s the funding for states, and then localities? States are facing incredible cuts to tax revenues. States are also resisting—especially New York State—raising revenue through progressive taxation. So, everything is on the chopping block. And unfortunately people who use drugs, LGBTQ people, people experiencing homelessness, have some of the greatest needs, but are not always a constituency that’s respected and valued, and gets those needs met.
So, we’re really facing a crisis, on top of a crisis, on top of a crisis, right now. And it remains to be seen how the federal government and congressional appropriators will respond. But there’s a lot on the line. And advocates hopefully, as Suraj was saying, will be coordinated and unified in their response so that we can at least mitigate some of the damage to public health and to other infectious diseases that the COVID pandemic has piled upon its devastation.