The approach may help curb the AIDS pandemic in poor countries and bring Gilead $1 billion a year in additional U.S. sales, said Josh Schimmer, an analyst at Leerink Swann & Co. in Boston. Most investors aren’t alert to the potential benefit, he said. Researchers are compiling the first data from 10 trials involving more than 20,000 people, and initial results may be available in July.
“This could be very meaningful for Gilead,” Schimmer said in a telephone interview. “You’re potentially treating 50 patients to prevent one. Commercially that’s very attractive. I don’t hear anybody talking about this, and I think all of us should be more aware.”
If the strategy works, the pills from Foster City, California-based Gilead may promise the world a powerful tool for fighting AIDS, the deadliest infectious disease, after scientists’ failure so far to develop an effective vaccine or virus-killing gel.
Skeptics say the approach, called pre-exposure prophylaxis, or PrEP, may be too costly and impractical in sub-Saharan Africa, where 22 million people are infected with HIV -- putting millions of others at risk -- and per-capita income is $951 a year.
Side effects may also undermine the plan. While doctors regard Gilead’s drugs as relatively safe, nobody knows what the medicines do in people who are taking them for a disease they don’t have, or how eager these patients will be to put up with the diarrhea, dizziness and depression the pills may cause.
‘High Tolerance’
“People have a high tolerance for side effects if it’s saving their life,” said Mitchell Warren, executive director of the New York-based AIDS Vaccine Advocacy Coalition, a nonprofit advocacy group. “It may be harder for healthy people to accept the side effects that come with prevention.”
The trials involve giving Gilead’s Viread and Truvada, the world’s top-selling AIDS medicine, to HIV-negative people from groups most at risk of contracting the virus, such as gay men who have unsafe sex and drug users who share hypodermic needles. Results from five of the studies may be available this year, according to the researchers running them.
One trial, scheduled to report data at an AIDS conference in July, is testing Viread as a vaginal gel in women who apply it before sex. Another is measuring the preventive effect of a daily Truvada pill among 3,000 gay men in six nations.
A further three studies coordinated by the U.S. Centers for Disease Control and Prevention, based in Atlanta, are testing PrEP among gay men in the U.S., drug users in Thailand and heterosexuals in Botswana. Gilead, while donating drugs and technical advice, isn’t running the trials, the company said.
Behavior Monitored
The studies are also designed to measure whether people receiving the drugs become riskier in their behavior, in the belief they’re protected against the virus. Participants receive testing, condoms and counseling on ways to avoid infection.
If the tests are successful, PrEP distribution programs could begin in developing countries in 2012, said Bill Gates, co-founder of Microsoft Corp. and the Bill & Melinda Gates Foundation, both of Seattle. He spoke to the U.S. Senate Foreign Relations Committee about global health priorities on March 10. The Gates Foundation is sponsoring three PrEP trials.
The CDC would try to issue guidelines on the use of PrEP to health-care providers within six months of successful test results, said Jennifer Horvath, an agency spokeswoman, in an e-mail.
First Defense
“PrEP is the next big thing,” said Warren of the AIDS Vaccine Advocacy Coalition, in a telephone interview. “We have a level of biological plausibility and early data in animal studies that is stronger than anything we have seen in the other approaches.”
Gilead had revenue of $7.01 billion last year, including sales of $5.54 billion from its top three AIDS drugs -- Truvada, Atripla and Viread -- which are taken by 85 percent of HIV patients in the U.S. as a first defense against the virus.
Gilead rose 17 cents, or less than a percent, to $45.64 at 4 p.m. New York time in Nasdaq Stock Market composite trading. The shares have increased 1 percent in 12 months. Investors aren’t sure what to make of the PrEP trials, said Jason Kantor, an analyst at RBC Capital Markets in San Francisco.
“This is not currently a focus for investors, and I have nothing in my estimates for this,” Kantor said an e-mail. “Positive data, if compelling, could be a small incremental benefit in the developed countries.”
Implications Unknown PrEP sales in the U.S. may range from “negligible” to as much as $1 billion annually, depending on the effectiveness of the drugs and how much patients and public-health agencies are willing to pay for prevention, Leerink’s Schimmer said.
Gilead itself doesn’t know what the commercial implications of PrEP might be, said Jim Rooney, the company’s director of clinical affairs.
“It’s going to depend upon the data,” Rooney said in a phone interview. “And it’s going to depend upon how the public- health officials evaluate the data and translate that into recommendations for clinical practice.”
Gilead will decide whether to seek regulatory approval of its drugs for prevention once results of the trials are known, Rooney said.
Doctors would be able to prescribe the medicines for prevention without the approval. A study published last year in the Journal of Acquired Immune Deficiency Syndromes found that among 277 gay men in Boston, one had used PrEP and 74 percent said they would use it if it were available.
Breast Milk
Drugs made by GlaxoSmithKline Plc of London and Boehringer Ingelheim GmbH of Ingelheim, Germany, are already used to prevent infected mothers from passing the virus to their babies in the womb or through breast milk. Glaxo’s Combivir is prescribed to prevent infections in men who take it after unprotected sex with an HIV-positive partner.
Those medicines show that using treatments as prevention can work, said Dawn Smith, a CDC researcher who is devising the agency’s plans to implement PrEP if the clinical trials succeed.
“I’m very hopeful that this approach will help to reduce HIV infection rates,” Smith said in a telephone interview. “But I’m enough of a scientist to be skeptical as well, and to want to see the trial results before I call myself a believer.”
Gilead’s drugs subdue HIV in infected patients by blocking an enzyme the virus needs to hijack cells in order to reproduce. Taken preemptively, the pills may prevent HIV from gaining a foothold when it first enters the body.
‘Good Reason’
A study presented at the Conference on Retroviruses & Opportunistic Infections, in Montreal last year, found Truvada cut the risk of infection almost 16-fold in monkeys. A 2007 trial of PrEP among 936 women in Africa concluded that a daily Viread pill cut the risk of infection by 65 percent, though the researchers said the trial didn’t produce enough data to prove conclusively that PrEP worked.
“From a scientific standpoint, there really is a good reason to believe that if properly done, it will work,” Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, based in Bethesda, Maryland, said at this year’s retroviruses conference, held in San Francisco in February.
There may be less reason to think PrEP is feasible, Fauci said.
“If we can’t get 70 percent of the people who are infected in low- and middle-income countries on therapy, how are we going to get people who aren’t even infected on therapy?” Fauci said.
If it does work, PrEP won’t come cheap. Giving Truvada to the 100,000 most at-risk gay men in the U.S. would cost more than $1 billion a year, the CDC said on its Web site. That sum covers only the cost of the pills, and doesn’t include marketing, HIV testing, and doctors’ visits.
‘Deep Down Horror’
Identifying people who are at sufficient risk of contracting HIV to receive PrEP will most likely be too difficult in Africa, where everyone who is sexually active is at risk, said Francois Venter, president of the Southern African HIV Clinicians Society, a professional group based in Johannesburg.
“Deep down I have this horror that we’ll have an effective intervention very few people are going to use,” Venter said in a telephone interview. “In America and Europe it’s probably going to be one of several interventions which are going to work. I worry that there hasn’t been enough focus on who’s going to take these drugs in my environment.”
To justify the expense of handing out drugs to people who don’t have HIV, the trials need to show that PrEP lowers the chances of infection by at least half, said Francoise Barre- Sinoussi, a French researcher who shared the 2008 Nobel Prize in medicine after helping to discover that HIV causes AIDS.
‘Little Bit Concerned’
“We will have encouraging information from those trials,” Barre-Sinoussi said in an interview in Singapore. “I’m just a little bit concerned about how to apply it at large scale.”
About 33 million people live with HIV, according to UNAIDS, the coalition of United Nations agencies formed to fight HIV. In 2008, 2.7 million people were newly infected with the virus and 2 million died from AIDS-related complications. Africa has 7 in every 10 of the world’s cases.
Assuming PrEP could prevent 50 percent of infections, it would almost cut in half the lifetime risk of catching HIV among high-risk gay men in the U.S., and almost triple the lifetime treatment costs, according to a computer simulation published in the journal Clinical Infectious Diseases in March 2009.
PrEP is “unlikely to confer sufficient benefits to justify the current costs” of Truvada in the U.S., researchers from Yale University in New Haven, Connecticut, and Harvard Medical School in Boston wrote in the study. The model assumed a drug cost of $753 a month for each patient.
Drug Costs Gilead sells a month’s supply of Viread to U.S. wholesalers for about $643. A month of Truvada costs about $930, said Cara Miller, a company spokeswoman, in an e-mail. The company charges people in poor countries about $17 a month for Viread and $26 for Truvada, she said. About 700,000 people worldwide take brand-name or generic versions of Gilead’s AIDS drugs, Miller said.
When the first AIDS drugs were approved in the U.S. in 1987, critics said they weren’t affordable in poor nations, the CDC’s Smith said. Now, about 40 percent of the patients who need them are getting the medicines, according to UNAIDS. PrEP may also prove more adoptable than its critics think, Smith said.
“If it’s highly efficacious, and if countries and UNAIDS and WHO and other public health agencies believe that it has a role to play in reducing new HIV infections, then we will find a way to make it available,” Smith said.
To contact the reporters on this story: Simeon Bennett in Singapore at sbennett9@bloomberg.net; Tom Randall in New York at trandall6@bloomberg.net
