Rhone-Poulenc Rorer Pharmaceuticals Inc. Statement US FDA Approval of Synercid(R) (Quinupristin/Dalfopristin) I.V.

COLLEGEVILLE, Pa. (PROTEXT) - The following statement wasissued today by Rhone-Poulenc Rorer Pharmaceuticals: Synercid(R) (quinupristin/dalfopristin) I.V., the firstinjectable antibiotic in a distinct class of antibacterials knownas streptogramins, was approved today by the U.S. Food and DrugAdministration (FDA) to treat bloodstream infections due tovancomycin-resistant Enterococcus faecium (VREF) and skin andskin structure infections (SSSI) caused by methicillin-susceptible Staphylococcus aureus or Streptococcus pyogenes.Synercid was developed by Rhone-Poulenc Rorer PharmaceuticalsInc. (RPR), a global pharmaceutical subsidiary of Rhone-PoulencS.A. (NYSE: RP). Synercid is the first antibiotic to be indicated for thetreatment of patients with serious or life-threatening infectionsassociated with vancomycin-resistant Enterococcus faeciumbacteremia. Certain strains of Enterococcus faecium have provento be resistant to virtually all available antibiotics -- untilnow. Synercid is active against these strains, although severalcases of emerging resistance occurred in VREF trials. The FDAalso approved Synercid to treat patients with complicated skinand skin structure infections caused by methicillin-susceptibleStaphylococcus aureus or Streptococcus pyogenes. One of Synercid's approved indications is for the treatment ofpatients with serious or life-threatening infections associatedwith vancomycin-resistant Enterococcus faecium (VREF) bacteremia.Synercid has been approved for marketing in the United States forthis indication under FDA's accelerated approval regulations thatallow marketing of products for use in life-threateningconditions when other therapies are not available. Approval ofdrugs for marketing under these regulations is based upon ademonstrated effect on a surrogate endpoint that is likely topredict clinical benefit. Approval of this indication is based on Synercid's ability toclear VREF from the bloodstream, with clearance of bacteremiaconsidered to be a surrogate endpoint. There are no results fromwell-controlled clinical studies that confirm the validity ofthis surrogate marker. However, a study to verify the clinicalbenefit of therapy with Synercid on traditional clinicalendpoints (such as cure of the underlying infection) areunderway. The two distinct antibiotic agents that form Synercid,quinupristin and dalfopristin, work synergistically to inhibit ordestroy susceptible bacteria through a two-pronged attack onprotein synthesis in bacterial cells. Without the ability tomanufacture new proteins, the bacterial cells are inactivated ordie. Synercid was studied globally in comparative clinical trialsfor skin and skin structure infections and in non-comparativeemergency use trials for VREF. The emergency-use program wasestablished by RPR in 1993 to provide doctors, upon request,access to Synercid to treat infected patients for whom no otheravailable drug was effective. Among the 1,222 enrolled patients, 27% did not have specificsite of infections but had two or more blood cultures with purevancomycin-resistant E. faecium. Ninety percent of these patientshad clearance of their bacteremia within the first 48-72 hours ofadministration of Synercid. The overall efficacy rate in thepatients who met strict clinical criteria (24.4% of overallpatients) was 52.3 percent. Additionally, two comparative studies of complicated skin andskin structure infections were conducted. In the combinedstudies, the overall efficacy rate for cellulitis, post-operativeinfections and traumatic wound infections was 63.4%, 36.8% and60.0%, respectively. The most common adverse drug reactions in comparative trialswere inflammation at the infusion site (42.0%), and pain at theinfusion site (40.0%). In three non-comparative trials, the mostcommon adverse drug reactions were arthralgia (7.8%, 5.2%, and4.3%), myalgia (5.1%, 0.95%, and 3.1%), both arthralgia andmyalgia (7.4%; 3.3%, and 6.8%), and nausea (3.8%, 2.8%, and4.9%). P450 3A4 substrates (e.g., cyclosporine A, midazolam,nifedipine, and terfenadine) should be used with caution andmonitored when coadministered with Synercid. Those drugs usedconcomitantly that may prolong the QTc interval should beavoided. Rhone-Poulenc Rorer is a global pharmaceutical companydedicated to improving human health. Rhone-Poulenc S.A. (NYSE:RP) is a leading life sciences company, growing throughinnovations in human, plant and animal health and through itsspecialty chemicals subsidiary, Rhodia. With sales in 1998 ofFF86.8 billion (US $14.8 billion; Euros 13.2 billion), thecompany employs 65,000 people in 160 countries worldwide. The RPRInternet web site is at http://www.rp-rorer.com. Note: Synercid full prescribing information available. Call Lise Geduldig at 847-275-5473, or Tom Jones at 212-448-4296. ots Original Text Service: Rhone-Poulenc Rorer Internet:http://www.newsaktuell.de Contact: Lise Geduldig, 847-275-5473,or Rick Roose, 610-454-5099, both of Rhone-Poulenc Rorer; or TomJones, 212-448-4296, or Rebecca Hamm, 212-448-4364, both ofKetchum, for Rhone-Poulenc Rorer Company News On-Call:http://www.prnewswire.com/comp/764050.html or fax, 800-758-5804,ext. 764050 Web site: http://www.rp-rorer.com

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