Bristol Reyataz Dosing For Renally-Impaired Patients Will Be Phase IV Study

FDA is requesting that Bristol-Myers Squibb determine appropriate Reyataz dosing for patients with renal impairment in a Phase IV study.

"Conduct a pharmacokinetic study of atazanavir in subjects with renal impairment to allow the determination of dosing for this population," FDA's ¹ Reyataz approval letter states. Bristol is directed to start the study by March 2004 and submit the final report by September 2006.

Reyataz (atazanavir) cleared the agency June 20 as combination therapy "with other antiretroviral agents for the treatment of HIV-1 infection" (² (Also see "Bristol Reyataz To Launch In July; Lipid Data Included In Labeling" - Pink Sheet, 23 Jun, 2003.), p. 27).

³ Reyataz labeling notes "in healthy patients, the renal elimination of unchanged atazanavir was approximately 7% of the administered dose. There are no pharmacokinetic data available on patients with impaired renal function."

FDA said it generally requests such data when a drug exhibits greater than 10% renal excretion. Since it is not known how much of the Reyataz administered dose is absorbed, the agency said it does not know the percentage of absorbed drug that is excreted by the kidney.

FDA requested similar studies for the two other most recently approved HIV therapies, Roche's Fuzeon (enfuvirtide) and Gilead's Viread (tenofovir).

Bristol has also committed to evaluate the long-term safety and efficacy of a Reyataz dose boosted with Abbott's protease inhibitor Norvir (ritonavir). The company conducted a study of ritonavir-boosted Reyataz but submitted only 16-week data in time for FDA review.

FDA noted that the boosted Reyataz study was specifically requested by the Antiviral Drug Products Advisory Committee during its review of Reyataz in May. The committee agreed the boosted atazanavir regimen demonstrated better efficacy in the treatment-experienced population and predicted it would be the dose most commonly used (⁴ (Also see "Bristol Reyataz Gets Broad Label Vote Despite Concerns In Drug Experienced" - Pink Sheet, 19 May, 2003.), p. 10).

Other Phase IV commitments include studying the long-term effects of atazanavir in fat redistribution. Although Reyataz had a smaller effect on lipid parameters than other protease inhibitors in clinical trials, atazanavir's favorable lipid profile did not result in fewer reported lipodystrophy events (⁵ (Also see "Reyataz Lipid Effect Offers Benefit But Not In Lipodystrophy, Cmte. Says" - Pink Sheet, 19 May, 2003.), p. 12).