By Brett Norman
03/10/2012
Source: Politico
A leading AIDS group is battling with FDA over whether the agency should approve the first drug for preventing HIV infection in gay men, and the fight has gotten nasty.
So nasty that last week the AIDS Healthcare Foundation called for Commissioner Margaret Hamburg to resign over that and other issues, perhaps including egos.
“The arrogance of the head of the FDA not being willing to meet with the largest AIDS organization in the world,” said Michael Weinstein, president of the Los Angeles-based AIDS Healthcare Foundation. “This is supposed to be the most transparent administration yet, but I haven’t seen any evidence of that.”
The fight is a reversal from the early days of the epidemic, when the advocates were pushing the FDA to speed up approval of the first generation of anti-retrovirals. In this fight, they want the agency to take it slow in considering Gilead’s blockbuster Truvada, already approved for use in treating HIV-positive people, as the first drug to be prescribed specifically for preventing HIV infection.
And Truvada has split the AIDS advocacy world, too. While the Healthcare Foundation is citing risks, some other groups are embracing the potential benefits. It’s a bit of a half-full, half-empty perspective arising from the clinical trial data.
One large international study released in 2010 found that Truvada cut the HIV infection in men who have sex with men by 44 percent compared to a placebo, when both were combined with free condoms, monthly counseling and regular testing for sexually transmitted diseases. So far, the drug has not been found to work in women.
The fear is that the drug will give men a false sense of security.
Weinstein contends that a 44 percent improvement is too low a bar, when condoms, properly used, protect against infection about 95 percent of the time. The drug also has significant side effects including potential kidney damage and can generate resistance to the drug that’s widely used to treat HIV infection. Weinstein worries that the promise of a “magic pill” could reverse progress the AIDS community has made in encouraging condom use over decades.
“You’ve got to really be paranoid about your pants falling down to wear a belt and suspenders,” Weinstein said. “There’s no reason to take this drug if you plan to use condoms, but it may well give people an excuse to stop using them. There’s a lot to lose.”’
The issue has caused a rift within the AIDS community as well, with other groups welcoming an alternative that could protect those who don’t wear condoms.
“This is new terrain in the AIDS world — it’s always been about treatment, and this is prevention,” said Jim Pickett, director of prevention advocacy and gay men’s health for the AIDS Federation of Chicago. His organization was one of 25 that penned an open letter to the FDA in support of Truvada for prevention after the AIDS Healthcare Foundation spoke out against it. “When [Truvada] is used, it works incredibly well and we have to figure out how to make it work in the real world outside of a clinical trial. I think it would be absolutely criminal for us to not do that.”
In the successful study, Pickett notes, the infection prevention rate was as high as 90 percent in those who took the pills consistently as directed. But patient adherence is a problem for all treatments and arguably more so for preventive ones.
The CDC estimates that about 50,000 people are newly infected with HIV each year, and more than half of those are men who have sex with men.
Last year, the agency put out an “interim guidance” for doctors prescribing Truvada off-label for protection against HIV infection, called “pre-exposure prophylaxis,” or PrEP. CDC said the drug could be an effective preventive measure for high-risk gay men, when combined with close monitoring to ensure they are actually taking the drug, counseling, access to condoms and regular screening for HIV and other sexually transmitted diseases.
“It’s like they thought [PrEP] approval was a done deal,” said Tim Boyd, public affairs manager for the AIDS Healthcare Foundation. He also said that in the real world, patients are unlikely to get all of the counseling and screening that were part of the successful international trial and the CDC’s recommendations.
In February, the FDA granted a “priority review” of the application, which is reserved for drugs that offer a major advancement in treatment or treatment where none other exists. And a decision is expected in June.
That sets the stage for a contentious FDA advisory committee meeting on the subject May 10. The agency is limiting the public comments to one hour, and advocates on both sides of the question intend to press their case.
In an irony for opponents, it was AIDS groups in the 1990s that pressured the FDA to limit the clinical trials required for approval of drugs to treat a disease that was then killing thousands of people a year.
“Back then, we wanted them to push the drugs out as fast as they could,” Boyd said. “Now we want them to slow down and take their time.”
An FDA spokeswoman declined to comment for this story.
David Kessler was FDA commissioner from 1990 to 1997 and worked to push through reforms that dramatically accelerated AIDS drugs development and helped make the first effective anti-retroviral “cocktail” treatment for the disease available in 1996.
Those reforms were codified in FDA’s “accelerated approval,” which allows drug developers to show that a treatment is effective against a surrogate marker of the disease, rather than its ability to cure the disease itself. That shortens the length of clinical trials, because researchers can look for signs that the treatment is working, rather than waiting to see, for instance, that a person is cured.
Accelerated approval is different from the “priority review” FDA granted Truvada in this case, which basically holds the agency to its usual standards for approval, but devotes more staff to do the review quickly.
In an interview, Kessler said the AIDS groups in the 1990s quickly became scientifically sophisticated and, once treatments were available, began to weigh in against allowing drug companies short-cuts on extensive clinical trials.
“When you have nothing available, and people are dying, you’re willing to try everything,” Kessler said. “When you have drugs that work, you try to optimize.”
He is not surprised by the different opinions of AIDS groups and said the robust discussion would help vet the complicated issues surrounding a drug for AIDS prevention.
“In the end, this is about risk and benefit,” he said. “If you look at the risks, are they acceptable in light of the benefits? That’s always the question, and there’s no computer program that you can feed in the risk and benefits and come up with a formulaic answer. There’s always a judgment call.”
As for Truvada, Kessler said “the good news is we can have the debate — which is a legitimate debate — in the environment of people having options not to die.”
