A long-anticipated new generation of AIDS drugs called protease inhibitors promises the most powerful medicine yet to stall - but not cure - the deadly virus, the nation’s top drug regulator says.
The remarks by FDA Commissioner David Kessler bode well for the first protease inhibitor, Hoffmann-La Roche’s saquinavir, which this week undergoes scrutiny by Kessler’s top advisers as they decide whether the drug should be sold.
Although he wouldn’t discuss saquinavir specifically, Kessler told The Associated Press: “There is no question this is the most active class of agents we’ve seen so far against the AIDS virus.”
The key is that protease inhibitors act on a different part of the human immunodeficiency virus’ life cycle than currently available drugs.
The future in AIDS therapy, Kessler declared, may be combining the two types of drugs “for a one-two punch.”
“The real breakthrough here will come from combination therapy,” he predicted.
Indeed, the Food and Drug Administration’s scientific advisers may essentially sound a death knell for single-drug therapy as they consider whether saquinavir and an unrelated but strong antiviral, called 3TC, boost the potency of standard AIDS treatment.
The panel will decide on Monday whether 3TC should be sold as a combination therapy with the older drug AZT, and on Tuesday whether saquinavir should get the same approval.
The two new drugs offer the potential to treat “AIDS and HIV as a chronic condition instead of a deadly disease,” said Omar Perez, health director of the National Association of People With AIDS.
Currently, there are just four anti-HIV drugs: AZT, ddI, ddC and d4T. Called nucleoside analogs, they work by blocking a protein active in the early reproduction cycle of the virus, but the virus quickly develops resistance to their effect.
Protease inhibitors block an enzyme called protease that is vital to the final stages of HIV’s replication. Three companies are developing the new drugs, but Roche beat the competition to the FDA and the agency found saquinavir so promising that it rushed the matter to the advisory committee just two months after Roche applied.
Studies show saquinavir in combination with AZT boosts the amount of patients’ vital immune cells, called CD4s, by an average of 70 cells per milliliter of blood, said Roche’s chief scientist, Dr. Keith Bragman. The amount of virus in patients’ blood plunged between 50 percent and 99 percent, and they experienced few of the side effects common with existing AIDS drugs, he said.
Also, HIV may not develop resistance to saquinavir as quickly, he said.
The drug 3TC is another nucleoside analog. When taken together with AZT, it, too, boosted CD4 levels by up to 70 cells, dropped patients’ virus content 50 percent to 90 percent and had few side effects, according to manufacturer Glaxo Wellcome Inc. More significantly, 3TC delayed the virus’ resistance to AZT.
Glaxo also found that 3TC worked just as well in children with AIDS, and will ask the FDA Monday to approve special strawberry-banana flavored drops for them.
But there are questions about these drugs - particularly, who should take them and when, and do they actually postpone death?
Nobody knows that yet because the FDA allows drugs for fatal diseases to be approved on the basis of quicker studies that track symptoms, not death, and no one has yet directly compared all the varying treatments.
Particularly with saquinavir, patients will face “a conundrum,” said Dr. Ellen Cooper of the American Foundation for AIDS Research.
There is some evidence that patients who develop resistance to one protease inhibitor won’t respond to any others, she noted.
And patients absorb only 4 percent of saquinavir, despite taking a massive 1,800 milligrams a day, she said. Other protease inhibitors appear better, but they’re about a year away.
Roche insists saquinavir isn’t cross-resistant and is so potent that the amount equal to two spoonfuls dumped in an olympic-size swimming pool inhibits HIV.
Patients typically absorb 10 times that, Bragman said, although Roche is developing a better formula.
Regardless, Cooper advises caution.
For early patients, “starting AZT and 3TC and saving the proteases until later … may well be the best way to go,” she said.