May 2, 2005

Coming Soon... A Kinder, Gentler Once-a-Day Kaletra?

FRIDAY, MAY 6, 2005

With headlines as bright as the big orange capsules of Kaletra itself, HIVers’ hopes were buoyed this week by word that yet another HIV med has entered the age of once-a-day dosing: Abbott Laboratories’ protease inhibitor (PI) can now be taken once—all six caps at a time—rather than twice daily. What’s more, the popular PI’s famous diarrhea distress may be on the wane, too, due to the capsule’s upcoming reformulation as a (fat-reduced!) tablet.

This good news for HIVers may be even better news for Abbott, which remains in the dog-house with AIDS advocates after jacking up the price of Norvir (a.k.a. ritonavir, the booster in Kaletra) by 400 percent last year. But the company’s own John Leonard, MD, told POZ the unprecedented price increase would pay for research aimed at just the sort of progress announced this week.

Of course, it pays HIVers to read the fine print. The once-daily dose is not for everyone: The FDA approved it only for patients just starting out on treatment, and you can’t take it with Sustiva or Viramune. So why are treatment-experienced HIVers left out of the fun? In a previous study of new-to-meds HIVers, once-daily Kaletra failed to maintain adequate blood levels of the med over the 24-hour period between doses—a potential danger for treatment vets who need maximum suppression, according to treatment advocate Tim Horn.

But Abbott researcher George Hanna, MD, told POZ that the company is “very interested in exploring” once-daily dosing for all. He says the only reason it’s not for vets now is that it hasn’t been tested in them, that dosing once a day achieves the same effect as twice—and that the study showing a problem with blood levels in once-daily dosing was flawed. With Abbott’s own longer and larger studies about to produce nearly two years of data, he says,  “We’re confident there won’t be any surprises—that they will confirm” that daily Kaletra successfully holds HIV in check when it’s only taken once a day.

Horn, for his part, is skeptical that once-daily Kaletra will pass muster for treatment vets. “For folks with drug-resistant virus,” he says, “once-daily Kaletra could be a minefield.”

POZ science editor David Gelman, MD, goes even further, asking why Abbott doesn’t just leave well enough alone. “Why mess with Kaletra’s reputation for generating little to no resistance over years when used as a first regimen? Why risk that with once-a-day dosing, which may weaken it—miss one dose, and you may be screwed.”

The prohibition on mixing non-nukes Sustiva or Viramune with once-a-day Kaletra may be a comparatively minor matter. The non-nukes both decrease Kaletra levels in your bloodstream. In twice-daily dosing, this is overcome by taking more Kaletra—eight a day instead of six. But “no data is yet available for how this effect can be overcome in once-a-day dosing,” says Antonio Urbina, MD, an HIV specialist at St. Vincent’s Hospital in New York City. Still, adds Gelman, a once-daily Kaletra/Sustiva combo makes little sense because Kaletra is taken with food and Sustiva without food—“It’s still two separate doses each day.” He also suggests that HIVers may not be very excited about taking a once-daily dose if it gives them more diarrhea, as it did in Abbott’s studies.

Turning Kaletra into a tablet may solve that problem. The current capsule version contains something called oleic acid—a fatty acid that can, in sufficient quantity, give you the runs. The new remix stabilizes the active ingredients in a fat-removed compound (Hanna says they’re looking into cutting the oleic acid in Norvir capsules, too): No oleic acid, no diarrhea and runs. That’s what Abbott hopes, anyway. The new version will also reduce the pill burden from six capsules to four tabs a day—and for the first time, there’s no refrigeration required.

Horn welcomes the prospect of fewer pills but calls the refrigeration issue a “minor advantage—nothing earth-shattering.”

Speaking of earth, however, the kinder, gentler new Kaletra will allow Abbott to storm markets around the globe where refrigeration is not readily available. Look for it sometime next year, proudly brandishing the “K” for “Kaletra”—although it looks like the company is hoping for more like “King of the PIs.”

But what inquiring minds really want to know is: Will the new K still be orange?

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