By 2002, Daria Hazuda had bet her career and several years of her life on what she hoped would be a groundbreaking HIV drug, one that could help save lives and reap huge profits for her employer, Merck & Co. Inc.
When the phone rang in her lab in West Point, Montgomery County, the news was bad: In tests, Hazuda's drug had sickened dogs. The results threatened to kill a project her superiors already were questioning because competitors' ideas seemed more promising.
"It was really devastating to the whole team," Hazuda said. "We had worked so hard."
Dead ends, however, had always spurred her on.
"It's like being a detective, putting the pieces together to make a story and seeing how those seemingly unrelated pieces can come together in that big eureka moment," said Hazuda, a fan of John le Carre's spy novels.
Despite the negative results in the dog tests, she and a team of hundreds around the world still believed that moment would arrive. They restructured the compound to eliminate the toxicities seen in dogs and brought Isentress to the market in 2007.
Their bet paid off. In the third quarter of this year, Isentress was Merck's fastest-growing drug, bringing in $197 million, an 84 percent increase from a year earlier.
The long road to developing Isentress highlights the challenges pharmaceutical companies face as they seek new drugs to replace billions of dollars in revenue that will be lost to generic competition in the next few years.
"It's the nature of the times. The public expects the drugs to have a nice safety profile, and so the process to develop drugs has become much more complex in the last few years," said Pablo Tebas, a doctor who directs the adult AIDS Clinical Trials Unit of the University of Pennsylvania and has consulted for Merck.
More important, Isentress represented a new method of attack on human immunodeficiency virus, which can cause AIDS. The virus mutates constantly, developing resistance to drugs and necessitating new ones.
For many patients, Isentress reduces the amount of HIV in their bodies, with fewer side effects than other treatments.
Tom McCoy, a Center City resident who is HIV-positive, said adding Isentress to his drug cocktail had helped him achieve a key treatment goal: The virus is undetectable.
"The best way to fight this disease is to take medicines that hit it from different angles, and Isentress is a different angle," McCoy said.
