An FDA advisory panel meets today to review a controversial move by Gilead Sciences to seek approval to market its Truvada HIV pill to prevent infection, which is also known as pre-exposure prophylaxis or PrEP. The move was both welcomed and criticized by AIDS activists, reflecting a spectrum of views on making a preventive pill available on a large-scale basis. To some, FDA approval would offer needed assistance in containing HIV and possibly clarify the extent to which such preventive measures are useful. To others, FDA approval raises the specter of creating a form of resistance to HIV due to widespread use, which would undermine effectiveness for existing Truvada patients and, therefore, diminish prevention efforts. In particular, critics worry people without HIV who take a preventive pill may engage in risky behavior. We spoke with Mitchell Warren, executive director at AVAC, about why the advocacy group supports PrEP…
Pharmalot: Why do you favor approval?
Warren: Taken together, all of the data begins to show us that if you take Truvada daily, you can get a substantial level of protection, up to 70 percent from HIV transmission. If you don’t take a pill you don’t get any benefit. What’s challenging is how do you help people who may be at risk adhere to the regimen? Those are programmatic issues that are really quite serious, but that’s not an aspect the FDA is likely to address.
Pharmalot: What data are you referring to? There seemed to have been contradictory results at one point.
Warren: As I look out over the last 18 month of results, there are different signals to digest. The first efficacy result was report in November 2010. There was a study of Truvada in men-on-men sex and showed 44 percent modest protection in six countries. Since then, there have been additional studies and they’re very complex results. On one hand, you can look at data and say it’s contradictory, but also say it’s beginning to tell a fairly consistent story. Another trial was stopped about a year ago after the DSMB (Data Safety Monitoring Board, at a schedule interim analysis, found there was no difference between the active and placebo arms, and recommended the trial be stopped… So if you look at those two trials, you could say it worked on men who have sex with men.
Then there was FemPrEP, which looked at just women taking PrEP in Africa and was stopped for futility. It was very confusing. But last July, at the International AIDS Society meeting, additional trial results were provided – a study in Botswana of heterosexual men and women (see here), and the Partners PrEP study, which was the largest and looked at Truvada and had people taking Viread alone. There were 5,000 couples and what was unique was about this was that one partner was HIV- infected and the other not infected. The HIV-negative partner was given Truvada, Viread or a placebo. The results showed both products – Truvada and Viread alone – were very effective in preventing transmission.
So across the studies there are different results, but more data was presented at a conference in March. The FemPrEP team presented additional analysis – 70 percent of women in the trial said they didn’t think they were at risk of HIV. And adherence data showed although there was very high self reporting of pill use, 30 percent of women had detectable drug. That means they weren’t taking the pill. And that’s why we saw no benefit in FemPrEP. The important comparison is the Partners study, where 80 percent had detectable drug. Partners showed Truvada provided 70 percent reduction in risk.
Pharmalot: What about the concern that some people may develop a form of resistance?
Warren: The most important part of PrEP, if approved, is to ensure there is testing on a frequent basis, probably on the order of every three or four months. We have to be sure before anyone takes PrEP they are HIV negative. The only cases of resistance in these studies came from people who initiated PrEP when they were already infected. We have to confirm HIV-negative status and have to be sure HIV monitoring is part of ongoing PrEP programs. Resistance is much more likely to develop and to be a concern in treatment than in prevention programs, because of the volumes. In prevention, people won’t get infected if they take the treatment effectively and won’t get HIV and so resistance wouldn’t develop.
Pharmalot: And why shouldn’t we be concerned about people thinking they can engage in risky behavior?
Warren: That certainly would negate the benefit. Most of that is about how we educate potential users of this product. This is partial protection. We see the same issues being raised around the world, such as in Africa where there’s discussion about male circumcision. People think it would provide added protection from HIV transmission. And people asked the same question – what about a subsequent increase in risky behavior? In male circumcision programs over the last five years, there’s no evidence of increased risk. It doesn’t mean it can’t or won’t happen, but there’s no evidence so far that it has. The issues need to b e very closely monitored in future programs.
Pharmalot: Still, people are people.
Warren: There needs to be an FDA requirement to Gilead about a REMS as part of any approval. We think the FDA should put requirements on Gilead to assure appropriate health educational materials are available for providers and users. So as a starting point, there has to be objective information about the use of mediation and prevention. This reality is going to be true of any prevention effort. If we don’t try to grapple with this issue programmatically to address the risk, knowing people are people, then we’ll never delivery anything in prevention or coming close to minimizing the impact of this epidemic. It’s one reason we’ve called for demonstration projects to learn how non-professionals can understand this and how we can counsel people.
And as part of approval, the FDA can insist on post-marketing surveillance and registers, which can’t be done when usage its off label. Others argue this would open the floodgates, but I think it’s absurd. PrEP is not going to be for everybody. It’ll be as a niche product. Some will use it for prevention some of the time, but not everybody will be able or want to take a pill every day for the rest of their lives for prevention. And no one is saying it should be rolled out for everybody to take the rest of their lives.
Pharmalot: And what about the cost? This is an expensive proposition that comes at a time when governments are strapped (read more here).
Warren: It’s a fascinating time. This exciting science is coming when we’re not doing so well economically. We’re hitting plateaus and this means we have to make some hard choices. In the US, Truvada is an expensive drug. It’s much less expensive in developing countries. The full list price in the US can be in excess of $10,000, but there are many programs that provide it much cheaper. Gilead provided a license for generic manufacturing in some countries, but it can still be expensive.
The question is whether PrEP can be cost effective? In certain scenarios, it can if it’s very well targeted at people who are at greatest risk and aren’t able to use condoms. There are mathematical models, but we don’t know yet programmatically how to do this. So whether the FDA approves or not, we need demonstration programs so we know what PrEP programs look like. As AIDS prevention, it’s not just a pill – it’s in the context of testing and counseling. Yes, cost is going to be a huge issue. But we shouldn’t ignore important logistical issues that paralyze us. Remember, 10 years ago, millions of people were not able to take these medications. There was no access and people said it wasn’t affordable. And now, these are being taken in developing countries and people are adhering to regimens, and the prices have come down. But I agree that cost may be the biggest challenge.
10 hours 45 minutes ago