By Charles Craig

The FDA approved Pharmacia & Upjohn's AIDS drug, Rescriptor, making it the second non-nucleoside reverse transcriptase inhibitor on the market and the 11th anti-HIV drug cleared for treatment of the disease.

Rescriptor (delavirdine) received expedited approval Monday despite a split vote in November 1996 from an FDA advisory panel on whether to recommend the drug for clearance. Some panel members were concerned clinical trial data were not sufficient to determine how Rescriptor should be used in combination with other antiviral AIDS drugs.

The advisory panel suggested post-marketing combination studies and the FDA agreed. John Ruane, a spokesman for Pharmacia & Upjohn, of Kalamazoo, Mich., said Monday clinical trials will be conducted to evaluate Rescriptor in three-drug and four-drug combinations with nucleoside reverse transcriptase inhibitors and protease inhibitors, which are the other two classes of drugs that attack HIV replication.

Boehringer Ingelheim GmbH, of Ingelheim, Germany, has the only other non-nucleoside reverse transcriptase on the U.S. market. The drug, Viramune (nevirapine), was approved in June 1996.

The FDA approved Rescriptor after considering results of a three-drug combination trial. The advisory panel only reviewed interim data from the study.

The three-drug trial evaluated Rescriptor in combination with AZT and ddI, two nucleoside reverse transcriptase inhibitors. The former is sold by Glaxo Wellcome plc, of London, and the latter is marketed by Bristol-Myers Squibb Co., of New York.

The interim data presented to the advisory panel demonstrated the triple combination increased CD4 cell counts compared with AZT and ddI alone. However, the three-drug regimen did not achieve as great an increase in CD4 cell counts as a previous trial where Rescriptor was paired with AZT. Those trial discrepancies caused some panel members to question how Rescriptor would be prescribed.

In complete findings from the three-drug study submitted to the FDA in February, data revealed Rescriptor with the other two drugs produced a greater reduction in viral load compared with AZT and ddI, but the addition of Rescriptor did not make a statistically significant difference.

Decrease in viral load and increase in CD4 cell counts are the two markers used to determine effectiveness of anti-HIV drugs.

The main side effect of Rescriptor was described as skin rash. Pharmacia & Upjohn also said a drug interaction study of Rescriptor and indinavir showed the former increased the blood level of the latter and if used together the dosage of indinavir should be reduced. Indinavir, whose brand name is Crixivan, is marketed by Merck & Co., of Whitehouse, N.J., and is the best selling protease inhibitor.

The most popular AIDS drug combination has been Crixivan with AZT (Retrovir) and 3TC (Epivir), both of which are sold by Glaxo.

Pharmacia & Upjohn said Rescriptor will be available in three to four weeks and will cost $2,250 a year.

Non-nucleoside reverse transcriptase inhibitors, like the nucleoside versions, attack HIV replication in the beginning of the cycle. Protease inhibitors, considered the most potent of the three classes of anti-HIV drugs, interfere with replication at the end of the cycle.

The difference between non-nucleoside and nucleoside compounds is the way they interfere with reverse transcriptase, an enzyme involved in viral replication. Nucleoside compounds are look-alike nucleic acids that interrupt the enzyme's replication activity. Non-nucleosides block the enzyme itself.

For treatment of AIDS, five nucleoside reverse transcriptase inhibitors and four protease inhibitors have been approved by the FDA in addition to the two non-nucleoside reverse transcriptase inhibitors.

Pharmacia & Upjohn's stock (NYSE:PNU) closed Monday at $35.875, up $0.125. *