New & experimental HIV treatments

FDA advisory panel says yes to tipranavir

Keith Alcorn
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The United States Food and Drug Administration’s Antiviral Drugs Advisory Panel voted 11-3 in favour of accelerated approval for the new protease inhibitor tipranavir (Aptivus) after public hearings yesterday in Washington DC.

Tipranavir is being recommended for approval in protease inhibitor-experienced HIV-positive patients, although the final labelling and approval must be decided by the FDA by June 22nd. The panel voted to recommend a twice daily dose of 500mg of tipranavir boosted by 200mg of ritonavir, as studied in phase III trials of the drug.

Tipranavir has been studied in two large trials in patients with protease inhibitor resistance (RESIST 1 & 2 studies), which showed that the drug was more effective than other boosted protease inhibitors when combined with at least two other drugs chosen after resistance testing (an optimised background regimen).

Glossary

Food and Drug Administration (FDA)

Regulatory agency that evaluates and approves medicines and medical devices for safety and efficacy in the United States. The FDA regulates over-the-counter and prescription drugs, including generic drugs. The European Medicines Agency performs a similar role in the European Union.

toxicity

Side-effects.

boosting agent

Booster drugs are used to ‘boost’ the effects of protease inhibitors and some other antiretrovirals. Adding a small dose of a booster drug to an antiretroviral makes the liver break down the primary drug more slowly, which means that it stays in the body for longer times or at higher levels. Without the boosting agent, the prescribed dose of the primary drug would be ineffective.

resistance testing

Laboratory testing to determine if an individual’s HIV strain is resistant to anti-HIV drugs. 

rash

A rash is an area of irritated or swollen skin, affecting its colour, appearance, or texture. It may be localised in one part of the body or affect all the skin. Rashes are usually caused by inflammation of the skin, which can have many causes, including an allergic reaction to a medicine.

Although the panel voted to approve tipranavir, they expressed caution and asked for further studies to be carried out to guide use of the drug.

In particular the FDA highlighted problems with potential drug interactions and liver toxicity. They noted that interaction studies looking at a wide range of cytochrome p450 enzymes and drugs metabolised through those pathways have not yet been carried out, despite the fact that tipranavir also inhibits CYP1A2, CYP2C9, CYP2C19 and CYP2D6. Grade 3 or 4 liver toxicity was noted in 10% of tipranavir treated patients, and emerged significantly more quickly in both RESIST studies. The same was true for triglyceride and cholesterol elevations.

A higher rate of rash was also seen in women than men treated with tipranavir in phase I and phase II trials, but no difference between the tipranavir group and the control group was seen in the RESIST studies. However the FDA says that the small number of women included in these studies makes it impossible to draw definitive conclusions.

“I clearly would urge the pharmaceutical sponsor, since we know that there is this persistent elevation in liver function studies, to generate data that lets us know the baggage with elevation over time,” committee member Lauren Wood (Uniformed Services University of Health Sciences) said.

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