Exploring the possibility of a three-way partnership to fight HIV and AIDS, Gilead Sciences Inc., Merck & Co. Inc. and Bristol-Myers Squibb Co. might bring together three marketed drugs into a single, fixed-dose product to provide a more simplified treatment option.
The product would include Gilead's Viread and Emtriva drugs, as well as Sustiva, a product marketed by both Bristol-Myers and Merck. If they come to terms, it would be the first agreement of its kind in the field of HIV.
The companies have been in discussions about a potential partnership for some time, but they decided to announce their talks on Sunday, following a speech given by U.S. Secretary of Health and Human Services' Tommy Thompson at the World Health Assembly in Geneva. Thompson commented on the need for increased treatment options for people with HIV/AIDS in the developing world. Gilead, Bristol-Myers and Merck hope to meet that need with the combination of their products.
"There's data that indicate that HIV treatment regimens need to be followed very strictly in order to be effective," said Jenna Conley, manager of public affairs at Foster City, Calif.-based Gilead. "The hope is that anything we can do to reduce the number of pills that people need to take can help patients achieve the goal of adhering to their regimen, and this becomes especially important in resource-poor settings."
Gilead's stock (NASDAQ:GILD) rose $1.87 on Monday to close at $57.60.
In his speech Sunday, Thompson announced an expedited review process for fixed-dose combination drugs (FDCs) and co-packaged HIV therapy drugs. The government would purchase such drugs under the president's $15 billion Emergency Plan for AIDS Relief and provide them at lower prices to millions of people in Africa and the Caribbean. Under the plan, the FDA could approve such FDCs and co-packaged products within six weeks of submitting an application.
Fixed-dose combinations - such as a Viread/Emtriva/Sustiva combination - co-formulate multiple medicines into a single tablet that could be dosed once daily. Also, the companies are considering co-packaging their products until the single-tablet form is available.
The government and various AIDS relief organizations have long been discussing the need for more therapeutics to treat HIV/AIDS. The changing disease requires the constant development of new drugs.
"AIDS is a very tricky virus, because it's constantly replicating," said Anita Larsen, a spokeswoman for Whitehouse Station, N.J.-based Merck. "It's like a chameleon. It's constantly changing as it gets into the DNA. HIV, in a word, mutates."
There are more than 20 HIV medications approved in the U.S.
Conley and Larsen both said it is too early to comment on the financial terms of the potential agreement between the companies. But Lester Crawford, the acting FDA commissioner, said the FDA is evaluating whether it can waive or reduce user fees charged to companies making new drug applications for those types of products. Typically, the FDA charges a user fee of more than $500,000. Thompson has urged manufacturers of brand name and generic drugs alike to submit applications for approval of FDCs.
To gain approval, Gilead, Bristol-Myers and Merck would need to do additional clinical testing using the Viread/Emtriva/Sustiva pill, if they finalize the agreement.
"We will need to conduct chemistry studies to demonstrate that the combined drugs don't react with each other," Conley told BioWorld Today. "Then, we'd do bioavailability studies to prove that blood levels of the product are comparable to what is achieved when they're used alone."
Gilead stepped ahead of the game when it filed regulatory applications in the U.S. and Europe for approval of a single-tablet, fixed-dose combination of Viread and Emtriva. A decision from both authorities is expected in early 2005. The company developed Viread in-house, but gained Emtriva through its 2002 acquisition of Durham, N.C.-based Triangle Pharmaceuticals Inc. (See BioWorld Today, March 16, 2004.)
Adding Sustiva (efavirenz) to the mix would introduce a drug of another class, making the product all the stronger, in theory. Both Viread and Emtriva are nucleoside reverse transcriptase inhibitor drugs, while efavirenz is a non-nucleoside reverse transcriptase inhibitor.
"The different classes attack the virus on different sides, in different ways," Conley said. "By using more than one class of drug, it enables you to fight HIV on more than one front."
Efavirenz, Larsen said, "halts the chain so the virus can't make copies of itself. Viread and Emtriva do the same thing, but in a slightly different way."
If the three companies prove the co-formulated drugs are effective and stable, with no change in the pharmacokinetic profile, then they could seek approval.
"We see no reason why the co-formulation might not reach the U.S. market in the 2006 time frame," stated a research note by analyst William Tanner of Leerink Swann & Co. in New York.
Tanner said a co-formulated version of the three drugs would provide "greater marketing traction" because it is combining into a single tablet two major classes of HIV therapeutics.
Viread (tenofovir disoproxil fumarate) was approved in October 2001. It had worldwide sales of $566.5 million in 2003. Emtriva (emtricitabine) was approved last July, and had U.S. sales of $10 million last year.
Sustiva, which received accelerated approval in 1998 and full approval in 2000, was discovered by Merck Research Laboratory in 1992 and was licensed two years later to Dupont Merck Pharmaceutical, which later became Bristol-Myers Squibb. New York-based Bristol-Myers markets Sustiva in the U.S., Canada and certain European countries, while Merck markets it elsewhere under the Stocrin brand name.