Nelfinavir (VIRACEPT«) Approved: Fourth Protease Inhibitor Available

On March 14 the U.S. Food and Drug Administration approved nelfinavir (VIRACEPT), for both adults and children, "for the treatment of HIV infection when antiretroviral therapy is warranted." The company announced that it expects the drug tobe widely available in pharmacies throughout the U.S. this week.

This approval is under the FDA's "accelerated approval" regulations, based on better improvements in viral load and other markers of disease progression in trials lasting 24 weeks, in patients on a three-drug combination of nelfinavir plus AZT plus 3TC, vs. those on AZT plus 3TC alone. Longer trials with nelfinavir are now ongoing. More than 1,000 people have received the drug in clinical trials, and an additional 3,000 have received it through an expanded-access program.

The recommended adult dose is 750 mg three times per day,with a meal or light snack. The FDA also approved dosage recommendations for patients 2-13 years old.

The FDA-approved package insert warns:

* "VIRACEPT should not be administered concurrently with terfenadine, astemizole, cisapride, trizolam or midazolam,because competition for CYP3A by nelfinavir could result ininhibition of the metabolism of these drugs and create the potential for serious and/or life-threatening cardiac arrhythmias or prolonged sedation."

Also, nelfinavir should not be coadministered with rifampin;and if coadministered with rifabutin, the dose of rifabutin should be reduced by half. For more information on these and other drug interactions, see the package insert.

"The most frequent adverse event associated with VIRACEPT is diarrhea, which can usually be controlled with non-prescription drugs, such as loperamide, which slow gastrointestinal motility" (from the package insert). Other possible side effects are listed.

Price and Reimbursement Assistance

Developer Agouron Pharmaceuticals, Inc. has set the"wholesale acquisition cost" for the adult dose of VIRACEPT at $15.48 per day ($5650 per year). This is in the middle ofthe price range for the other three protease inhibitors. "To facilitate patients' access to VIRACEPT, Agouron has established a patient assistance program to actively help people to find ways of paying for VIRACEPT. Agouron will provide VIRACEPT without charge to those patients whose needis greatest and who are least able to pay for the drug. In addition, Agouron will provide VIRACEPT to any child in the United States who is not covered by public or private health insurance. For information on the VIRACEPT Assistance Program for both adults and children, call toll free 1-888-777-6637.

"Agouron will make VIRACEPT available to all AIDS DrugAssistance Programs (ADAPs), including those that purchase products through government-discounted pricing, and will offer rebates to any ADAP that is unable to purchase products at the government-discounted rates. In addition, Agouron will make VIRACEPT available to Medicaid."

Comment

There had been uncertainty over whether a 500 mg or 750 mg dose would be approved, with many physicians who had worked with the drug wanting the higher amount. The central issue around the dose is that the 24-week trials do not show a difference between 500 mg and 750 mg; however, there are reasons to be concerned that the virus may be more likely to"escape" from the lower dose by developing drug-resistance mutations. Also, approval of the higher dose gives doctors more flexibility -- since if the low dose were approved,insurance companies and other payers would probably balk at paying for more of the drug when doctors wanted to use it,whereas payers would be unlikely to object to doctors using a dose less expensive than the one approved.