HIV Drug Development Falters as Merck, Bristol-Myers Struggle With Success
March 14, 2011
By Michelle Fay Cortez
Gilead Sciences Inc., the world’s biggest AIDS-drug maker, revolutionized treatment and helped forge a $15 billion market with a single daily pill attacking the virus with three medicines at once.
Now, Foster City, California-based Gilead and rivals Merck & Co. and Bristol-Myers Squibb Co. are victims of that success. Three decades after the discovery of the virus that causes AIDS, there are 31 drugs on the market that have helped turn HIV from a death sentence into a manageable disease in the developed world. Only six were approved after 2004.
“The bar for bringing on a drug in HIV has gotten higher,” said George Hanna, vice president of virology for U.S. medical and HIV early development at Bristol-Myers, based in New York. “You can no longer bring to market a drug you’re going to have to take three times a day. All of a sudden, we’re seeing a lot less in the pipeline.”
Medicines created over the years have become safer, more effective, have attacked the virus in new ways and have eliminated the need for as many as 20 pills a day. As drugmakers struggle to top that achievement, millions of HIV patients face the possibility of the virus becoming fatal again if it shifts shape inside cells to outsmart existing therapies.
HIV has been a formidable foe for drug designers, mutating around chemical hurdles placed in its way. The attack begins when the virus attaches to a cell surface receptor and uses a protein to force its way inside. Most existing families of drugs stop HIV from hijacking proteins to enter cells or block its ability to copy itself once inside.
Without a steady stream of new medicines to attack the virus in different ways, drug resistance will develop, leaving more patients without a viable treatment, said Scott Hammer, a professor of medicine at Columbia University in New York.
“If we are complacent, resistance will start to spread against the key components of our therapies,” Hammer said in an interview. “We need to be ready for that because we won’t be able to catch up after it happens.”
Gilead generated $6.3 billion from HIV drugs in 2010, capturing more than 40 percent of the market. Atripla, a three- drug combination pill approved in 2006, is the most widely used AIDS medicine. It mixes Gilead’s two-drug medicine Truvada, approved in 2004, with Bristol-Myers’s pill Sustiva.
Pfizer Inc. and Merck were the last to introduce new families of medicine for HIV in 2007. Selzentry, the first AIDS drug to block the CCR5 pathway that allows cell entry, generated $128 million last year for New York-based Pfizer and its partner GlaxoSmithKline Plc. Merck, based in Whitehouse Station, New Jersey, had 2010 sales of $1.1 billion for Isentress, which inhibits the integrase protein used by HIV to enter healthy immune cells.
Intelence, from New Brunswick, New Jersey-based Johnson & Johnson, was the last AIDS drug approved -- three years ago.
At that time, there were seven drugs in the third and final stage of testing needed for U.S. regulatory approval, according to a report by Treatment Access Group, an AIDS activist and research organization. None have made it to the market, and only two of them remain in third-stage testing.
There are about 60 drugs in various stages of development for HIV, down from 100 in 2006, said Courtney Stanton, an analyst in the infectious diseases group at Decision Resources in Burlington, Massachusetts. Ten were discontinued or put on hold in the past year, while seven now are at the end of development, she said.
Recent failures by Merck and Avex Ltd., an Australian biotechnology company highlight the difficulty drugmakers face in coming up with a medicine that advances HIV treatment.
Merck ended work on vicriviroc, a drug similar to Selzentry, in previously treated patients in January 2010 after it failed to outperform existing therapies. Avexa, an Australian biotechnology company, scrapped apricitabine last May after five years of development. The drug was taken twice daily, putting it at a disadvantage to Gilead’s Truvada, one of the best-selling HIV treatments.
The availability of powerful combination treatments in the developed world means the number of people desperate for new drugs and available to participate in studies has plummeted, Decision Resources’ Stanton said.
“There are very few HIV patients now who can’t find effective treatment,” she said in a telephone interview. “And it’s become extraordinarily hard to show you are effective in a treatment-experienced HIV patient.”
The development process was more productive around the turn of the century. HIV was evading existing treatments, like London-based Glaxo’s AZT and Merck’s Crixivan, and drug- resistance was spreading. Doctors and patients clamored for additional options, and clinical trials were in demand as the only way to get the newest treatments. A better understanding of the virus gave drugmakers numerous targets.
Drug studies are also taking more time to complete, said Norbert Bischofberger, Gilead’s chief scientific officer. The FDA now wants 48 weeks of data, and will ask companies to keep patients in the study for longer, up from 16 weeks initially, he said. Doctors want to see two or three years of data before putting their patients on a drug. European regulators have proposed extending the studies further to 96 weeks, he said.
“Honestly, that’s probably a good thing,” Bischofberger said. “It reflects that we have really good regimens.”
Gilead is fashioning a new mixture dubbed B-tripla that replaces Bristol’s Sustiva in Atripla with Johnson & Johnson’s drug TMC278. It also has a four-drug cocktail in development called Quad that uses all Gilead products. Longer term, Gilead is examining ways they could deliver HIV drugs once a month or even less frequently, as with some contraceptives, he said.
33 Million People
The number of people with HIV continues to grow. Each year, 56,000 Americans are infected with the virus, particularly gay men and minorities, according to the Centers for Disease Control and Prevention. There were 2.6 million new infections globally in 2009, with more than 33 million people living with the virus, according to UNAIDS. Now, the ultimate goal is a cure.
“The profit motives that drove HIV drug development are no longer there because the drugs are so good,” said Jacob Lalezari, director of Quest Clinical Research, a San Francisco clinical trial center, said in an interview. “It’s the greatest success of western medicine in our lifetime. And the success of HIV drugs is leading to its own demise.”
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