Wall Street Journal - July 10, 2006
David P. Hamilton, david.hamilton@wsj.com

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.

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John Carreyrou contributed to this article.

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