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Postition Paper on FDA Approval of Atazanavir (Reyataz)

June 2003

By Rob Camp

To lipid it or not to lipid it

From the Introduction

Atazanavir (ATV) is an azapeptide protease inhibitor under development by Bristol- Myers Squibb, licensed from Novartis. Overall, the drug looks virologically similar to nelfinavir (NFV) in phase II/III clinical trials, with fewer effects on lipids.

Atazanavir should be taken with a “light meal.” It is available orally as 100mg, 150mg and 200mg capsules, and as a powder that can be mixed with juice or milk. Capsules should be stored at room temperature, 15-30 C (59-86 F).

Atazanavir is being reviewed as a protease inhibitor (PI) for people with HIV starting their first treatment regimen with a PI. That is where it will have best effect as an unboosted PI. If resistance to other PIs is present, ATV will probably lack potency as a single PI due to cross-resistance. It is being investigated with a 100 mg ritonavir booster, although no data on this combination have yet been published. Pharmacokinetic studies indicate that ATV 300/r100 is at least as good as ATV 400.

Based on data from ongoing and completed studies, specifically the 008, 009, and 034 studies, TAG and the undersigned organizations believe that the FDA should approve the Bristol-Myers Squibb application for accelerated approval of Reyataz® brand atazanavir (NDA 21-567 and 21-568) to treat HIV infection in combination with other antiretroviral agents in adults, provided that the follow up studies recommended below are commenced and successfully completed in a timely fashion.

  • Dosing: comparing 400mg QD with 600 & 800 mg.
  • Switch studies to ATV from other PIs, efavirenz and nevirapine.
  • Drug-drug interaction/PK studies with methadone, H2 blockers, rifampin, statins, fibrates, ribavirin, efavirenz, nevirapine, tenofovir, fosamprenavir, saquinavir (Invirase and Fortovase), and pegylated interferon.
  • Pediatric studies to determine safe and effective dose regimens.
  • Studies to determine the significance of ATV-associated changes in QT intervals.
  • Further studies of hyperbilirubinemia and ATV’s effect on people with compromised liver function.
  • Long-term safety studies.
  • Studies to determine the impact of ATV + ritonavir on lipid levels and CVD risk factors.
  • Resistance studies, including the relationship between the I50L mutation and potential hypersusceptibility to other PIs.
  • Studies in PI-pretreated individuals, comparing ATV/r to lopinavir/r and other second line and salvage regimens.
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