3 new drugs for HIV are raising hopes

Posted: July 15, 2007

For 27 years, James Vokoun has had HIV, the virus that causes AIDS, and it was growing increasingly resistant to drugs. Vokoun, 48, of Holland, Bucks County, felt a crushing fatigue all the time, as if he were perpetually getting the flu.

Then in January, he started taking an experimental HIV drug made by Merck & Co. Inc. Within a month, the virus was undetectable in his system for the first time since he learned he had it. This spring, he felt good enough to help plant lilacs, which would have been unthinkable a year ago.

"People are under the impression that HIV is very manageable, but it's not," said Vokoun, a former corporate compensation analyst. "Now I see hope not only for me, but for a lot of other people."

Doctors know that any single experience can be a fluke. The drug, Isentress, has been tested for a brief time in just 800 people. And it is not even approved by the government, though that could happen soon.

Still, the drug is causing a stir in HIV circles. Experts say it is one of three experimental compounds - Pfizer Inc.'s Celsentri and Tibotec Inc.'s Etravirine are the others - that appear to help the sickest HIV patients, those with multiple drug resistance.

Two of those drugs - Isentress and Celsentri - could represent the first new classes of oral HIV drugs approved in more than a decade.

"It's a very exciting time for HIV therapeutics," said Pablo Tebas, a physician who directs the adult AIDS Clinical Trials Unit of the University of Pennsylvania. "We have more drugs than ever. We have new drugs in new classes. It has increased our armamentarium to treat patients."

"There really is a lot of optimism about this," added Murray Penner, deputy executive director for domestic programs at the National Alliance of State and Territorial AIDS Directors in Washington.

Penner's interest is more than professional. He learned he had HIV in 1986, and his HIV blood levels have recently kept spiking despite the meds he is taking. "I'm at the end of my rope," he said.

So he was planning to start on Isentress and Etravirine late last week.

Acquired immune deficiency syndrome, or AIDS, remains a fatal disease. The HIV virus, which is spread through sexual contact and infected needles, has led to the deaths of more than 25 million people worldwide since 1981 and currently infects about 40 million people.

In the United States, more than 550,000 have died, and about 1.2 million people are infected, according to the Centers for Disease Control and Prevention.

The Philadelphia region remains a prime site for the epidemic. New Jersey and Pennsylvania ranked fifth and seventh in the United States in the number of AIDS cases in 2005.

A range of new drugs has blunted HIV's deadly effects, converting it into a chronic disease, at least for those with health insurance. AIDS deaths peaked in the United States in 1994 and 1995, after two new classes of drugs were introduced, including the first protease inhibitor. That class helped drive down the epidemic's mortality 70 percent by limiting the virus' ability to reproduce.

But researchers are still locked in a continuous race with the virus, which keeps mutating and finding ways to dodge the drug cocktails thrown at it.

Consider that 23 single agents have been approved for HIV in four classes, said Karam Mounzer, medical director of Philadelphia Fight, the comprehensive AIDS clinic in Center City, which helps test many HIV drugs, and offers all three new compounds to those who qualify.

But at least 25 percent of his patients have developed extensive resistance to those drugs, he said.

Other doctors put the drug-resistant population in their practices as high as 40 percent to 50 percent.

So the new drugs come in the nick of time for some patients. "It's really wonderful all these drugs are becoming available at the same time," said John D. Baxter, medical director of the Early Intervention Program at Cooper University Hospital.

Isentress inhibits the integrase enzyme, which is critical for HIV's replication. Nearly two-thirds of those with drug resistance had their virus levels fall to undetectable levels while using Isentress and two other agents, according to a pair of studies released in February. That compares with about one-third whose virus levels became undetectable while solely on the other agents.

"The slope of that downward curve looks about as sharply down as we have seen," observed Jeffrey Jacobson, chief of the division of Infectious Disease and HIV Medicine at Drexel University College of Medicine.

So far, the drug appears low on side effects, doctors say. A few patients in the clinical trials developed cancers related to HIV, but the data do not show they were caused by the drug, said Robin Isaacs, Merck's executive director of clinical research.

About 800 patients have participated in clinical trials of Isentress, and an additional 3,500 are receiving the drug free through expanded access, Isaacs said. Isentress is scheduled to go before the U.S. Food and Drug Administration's advisory committee Sept. 5 and could get sales approval by mid-October.

Merck's HIV sales were $327 million in 2006, just 1.5 percent of its $22.6 billion in sales.

Pfizer's Celsentri received a unanimous recommendation for approval from an FDA panel in April, and it is awaiting final FDA action. The drug binds with a receptor on white blood cells and prevents HIV from entering the cell in that way.

But it cannot prevent HIV from using a second receptor that often shows up often late in the disease progression. That means the drug will work in only about half of HIV patients. Those who use Celsentri will need an expensive test to determine if they will be helped.

Etravirine is part of an existing class of drugs, the nonnucleoside reverse transcriptase inhibitors (NNRTIs), which already are facing resistance. But a trial released this month showed that 62 percent of those taking the drug in a cocktail combination had undetectable levels of HIV vs. 43 percent in the comparison group.

Doctors are concerned about the likely high cost of all three drugs when they hit the market. Also, their long-term side effects will not be known until many more people use them.

Still, many doctors say they believe the drugs could take the epidemic into a new phase. "We have three new drugs, all potent," said William Towner, a physician with California-based Kaiser Permanente, which had the largest number of U.S. enrollees in the Etravirine study. "Being undetectable is now a goal again."


Getting the New HIV Drugs

All three new HIV drugs may be available through expanded access programs. But patients must show they can't use existing drugs.

Isentress: Call 1-877-327-6751 or go to http://www.earmrk.com/

Celsentri: Call 1-888-275-4478 or go to http://www.maraviroceap.com/

Etravirine: Call 1-866-889-2074 or e-mail to TMC125EAP@ i3research.com

Sources: Firms


Contact staff writer Karl Stark at 215-854-5363 or kstark@phillynews.com.

 

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