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New 3-Drug HIV Pill of Sustiva+Truvada: approval close, perhaps 'this week'
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"New AIDS Pill Simplifies Treatment FDA Is Close to Approving
A Once-a-Day Medicine That Combines Three Drugs"
Wall St Jnl
By DAVID P. HAMILTON
July 10, 2006; Page B8
AIDS patients, who have long endured drug regimens requiring them to swallow multiple pills each day, may soon have a much simpler option: a triple-combination "cocktail" in a single daily pill.
The new pill is the result of an unusual corporate joint venture between Gilead Sciences Inc., a Foster City, Calif., biotechnology company emerging as a major player in the market for AIDS drugs, and Bristol-Myers Squibb Co., an established pharmaceutical giant. Despite a complicated history, the two partners managed to forge one of the first ventures in which drug makers have combined their proprietary AIDS drugs into a single pill.
That as-yet-unnamed "triple pill" could greatly simplify the lives of AIDS patients, who currently must take at least two pills a day, and often more. Some doctors expect that the triple pill will quickly emerge as a front-line treatment for newly diagnosed AIDS patients because of its ease of use.
Widespread use of the combination drug could potentially even slow the spread and evolution of the AIDS epidemic itself. Drug-resistant strains of HIV, the AIDS virus, often emerge when patients accidentally skip doses of their medications -- an easy mistake to make when taking multiple pills at different times of day.
A single daily pill should be far easier for people to take as directed. If that results in a lower level of drug-resistant HIV, patients will tend to remain healthier for longer periods, and the virus is less likely to spread, doctors say. That is significant for the U.S. and other industrialized countries, but potentially groundbreaking for Africa and the rest of the developing world.
"Certainly in the African setting, it will have a huge impact," says Tom Coates, associate director of the AIDS Institute at the University of California at Los Angeles. "If you can get good viral-load suppression in a population, you're going to get lower transmission of the virus." Other AIDS experts warn that any disruption of antiviral supplies in the developing world might make it easier for resistant strains of the virus to evolve.
The Food and Drug Administration could approve the new daily pill soon, possibly within the next several weeks. The FDA has pledged to expedite approval applications for such combination pills in as little as two to six weeks. Gilead and Bristol, New York, submitted their triple-pill application at the end of April.
The triple pill isn't a panacea. Like other AIDS treatments, it suppresses the replication of HIV, but doesn't eliminate the virus or cure AIDS. The three drugs contained in the pill -- Viread and Emtriva from Gilead and Bristol's Sustiva -- are generally less toxic than older alternatives, but as a group they may still increase the risk of kidney and liver problems and neurological side effects.
Although Gilead and Bristol haven't announced pricing for the triple pill, officials at both companies suggest it may cost about the same as its separate components. If that is true, a year of the triple therapy would cost close to $14,000 in the U.S. In the world's poorest nations, where Gilead and Merck & Co., which sells Sustiva in many overseas markets under the name Stocrin, both sell their respective drugs at a "no profit" price, the same yearly treatment would cost nearly $600, more than four times the cost of a generic triple-combination pill made from older AIDS drugs and widely available in the developing world.
Triple-combination therapy emerged a decade ago and all but overnight transformed AIDS from a near-certain death sentence to a manageable chronic disease. The treatment was anything but easy for most people. In addition to sometimes severe side effects, patients could end up taking nearly 30 pills every day -- some with food, others without, three times a day.
Newer drugs have simplified that regimen. In the U.S., some physicians say that half or more of all newly diagnosed patients take two pills a day -- Sustiva and Truvada, a pill from Gilead that combines Viread and Emtriva. Over time, however, many people end up moving to more complex combinations in an effort to keep a step ahead of their ever-evolving virus. Some studies suggest new AIDS patients move on to a second combination in just 12 to 18 months as their virus evolves.
The idea for the triple pill originated with Bristol, which in 2003 contacted Gilead to suggest a collaboration. The two sides knew one another already, as Gilead Chief Executive John Martin had worked at Bristol before joining Gilead.
That didn't mean the two companies saw eye to eye. "Frankly, we were quite skeptical," says John Milligan, Gilead's chief financial officer. Gilead's first major product, Viread, itself derived from a chemical compound Bristol had once owned, had succeeded largely at the expense of an older Bristol AIDS drug called Zerit. "The level of trust wasn't there," Mr. Milligan says.
Despite their misgivings, the two companies began negotiating. They drew in Merck. Yet progress was slow as the parties wrangled over details of who would manufacture the combined pill, who would sell it, how to share revenues and profits, and even what the joint venture would be named. Antitrust considerations prevented them from even discussing how to price the triple pill.
The following April, the FDA called a surprise meeting with the three companies at which agency officials urged them to combine their AIDS drugs into a single pill. The agency had become more outspoken on the subject as part of a major Bush administration initiative to provide AIDS drugs throughout the developing world. In May, the three companies announced their intent to collaborate, although they wouldn't hammer out a final contract for a further seven months.
Gilead, meanwhile, had begun the chemical work necessary to combine the drugs in hopes of saving time, even though the company stood to lose its investment if the proposed joint venture fell apart. The job proved trickier than expected, in part because Truvada and Sustiva interfered with each other when simply mixed together, lowering the levels of circulating drug in the bloodstream. Its first four tries fell flat, although a fifth attempt in which the company's chemists packed the two drugs in a bilayer formulation that allowed each to dissolve at its own pace.
The Gilead-Bristol partnership is the first of what many AIDS experts hope will be additional collaborations aimed at simplifying triple-combination therapy. "I hope it's a harbinger," says Howard Grossman, executive director of the American Academy of HIV Medicine in Washington. "Just getting lawyers to agree like that is amazing." So far as Dr. Grossman and other experts can tell, the Gilead-Bristol effort is the only such venture of its kind.
"New Medicine for AIDS Is One Pill, Once a Day"
NY Times
By ANDREW POLLACK
Published: July 9, 2006
The first complete treatment for AIDS that is taken once a day as a single pill is expected to be available soon.
The pill, which combines three drugs made by two companies, would be a milestone in improving the simplicity of treatment for the disease, experts say. It should make it easier for people to take their medicine regularly, which is important for keeping the virus that causes the disease in check.
Only a decade ago, when cocktails of AIDS drugs were first used, patients often had to take two or three dozen pills a day, some with food, some without, some so frequently patients had to get up in the middle of the night. Since then, the regimens have been whittled down to as few as two pills a day, and now, one.
"Going down to one pill a day is amazing," said Keith Folger of Washington, who started on 36 pills a day about 11 years ago and expects to switch to the new pill when it becomes available.
Mr. Folger, who is just leaving a job as director of community mobilization for the National Association of People With AIDS, said the pill would be "remarkable, especially for people who are starting on medication for the first time and are sort of freaked out that they will have to take pills for the rest of their lives."
The new drug is a combination of drugs already on the market - Sustiva, sold by Bristol-Myers Squibb, and Truvada, sold by Gilead Sciences. Truvada is a combination of two Gilead drugs, Viread and Emtriva.
The Food and Drug Administration is expected to approve the new drug as soon as this week. The agency has until October to act but is expected to do so much sooner, partly because the government has been encouraging companies to do just this sort of collaboration to come up with simpler AIDS drugs.
The companies have not revealed the new drug's name or its price, though they have suggested it will cost roughly the same as Sustiva and Truvada bought separately, which is about $1,200 a month.
There are already other AIDS pills that combine three drugs. One, made by a company in India, was recently approved by the F.D.A. for use in developing countries. But those other three-in-one pills generally contain older drugs and are taken twice a day.
The drugs in the new pill already constitute the most widely prescribed regimen in the United States and one of the most effective.
Doctors and securities analysts expect most people now taking Sustiva and Truvada separately to switch to the new pill.
It is somewhat less certain how many people taking other drug combinations will switch. Some of them will not because the virus in their bodies is already resistant to one of the drugs in the new pill or because they cannot tolerate side effects. Sustiva, also known as efavirenz, can cause unsettlingly vivid dreams and birth defects.
In addition, the new salmon-colored pill is about 1,500 milligrams, the size of a large vitamin pill, and some people may find it difficult to swallow.
Going to a single pill could be especially important in poor countries, where patients have less access to medical care and more people are illiterate or uneducated. The vast majority of the nearly 40 million people in the world infected by H.I.V., the virus that causes AIDS, are in developing nations. In the United States there are about 1.1 million.
Bristol-Myers and Gilead say they will make the new pill available at a sharply reduced price for developing nations, but details are still being worked out. They are negotiating with Merck & Company, which sells efavirenz in those countries under the name stocrin.
A once-daily treatment did not become feasible until a few years ago, with the development of individual drugs that needed to be taken only once a day.
Still, no one company controlled all the drugs needed for an effective combination. It is rare for rivals to collaborate, though it has been done. Merck and Schering-Plough, for instance, have put two of their drugs into a combination cholesterol treatment called Vytorin.
Executives at Bristol-Myers, discussing in 2003 how to increase sales of Sustiva, came up with the idea of approaching Gilead, which already had two once-a-day pills, Viread, also known as tenofovir, and Emtriva, or emtracitabine. Gilead, based in Foster City, Calif., is now the largest supplier of H.I.V. drugs.
Talks were given further urgency when the F.D.A. summoned the two companies and Merck to a meeting in Washington in April 2004. The government was trying to encourage development of simpler pills as part of the president's plan to provide antiviral treatments to poor countries. The next month, the three companies announced their plan.
But carrying it out was not easy. Simply combining the three chemicals produced a mixture that melted easily.
"We made the first formulation and went out for lunch, and when we came back from lunch we had glue on our hands," said Reza Oliyai, a Gilead scientist. The eventual solution was to keep Truvada and Sustiva in separate layers.
It also took about a year to find a formulation that would produce the same level of the three drugs in a patient's blood as the three drugs taken separately, which is the main requirement for approval of a combination drug. Gilead tested five different formulations in healthy volunteers.
The failure of patients to take their drugs faithfully is a major problem, experts say, because it allows H.I.V. to develop resistance to the drugs.
Still, it is unclear exactly how much better people with H.I.V. will stick to a once-daily regimen compared with one requiring two pills a day.
Bob Huff, who edits a newsletter on new treatments for the Gay Men's Health Crisis, a patient advocacy group in New York, said a drug's potency and side effects were more important to patients than convenience.
Still, he said, "For some people it's just what they need to make treatment doable." A single pill may also mean a single insurance co-payment, he said, instead of two or three now that can cost people $100 a month.
Michael Weinstein, president of the AIDS Healthcare Foundation, a Los Angeles organization that runs clinics in the United States and abroad, said other problems besides inconvenience - like drug addiction, depression and mental illness - kept people from sticking to their AIDS drugs.
Still, Mr. Weinstein called the new pill a "high-water mark" for simplicity and the way it was developed. "To have two companies collaborating - that's going to be significant for the future if it sets an example."
While other companies are expected to try to develop once-daily treatments, no other existing drugs can yet be as readily combined, said Dr. Calvin Cohen, research director for the Community Research Initiative of New England, a nonprofit organization that does clinical trials of H.I.V. drugs and provides patient education.
Dr. Cohen, an adviser to Gilead, Bristol-Myers and other drug manufacturers, said there was already some concern among AIDS experts that having a once-a-day treatment would make people lose their fear of H.I.V. "We still want people to respect that prevention of the disease is better than treatment," he said.
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