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

COLLEGEVILLE, Pa. (PROTEXT) - The following statement was issued today by Rhone-Poulenc Rorer Pharmaceuticals: Synercid(R) (quinupristin/dalfopristin) I.V., the first injectable antibiotic in a distinct class of antibacterials known as streptogramins, was approved today by the U.S. Food and Drug Administration (FDA) to treat bloodstream infections due to vancomycin-resistant Enterococcus faecium (VREF) and skin and skin structure infections (SSSI) caused by methicillin- susceptible Staphylococcus aureus or Streptococcus pyogenes. Synercid was developed by Rhone-Poulenc Rorer Pharmaceuticals Inc. (RPR), a global pharmaceutical subsidiary of Rhone-Poulenc S.A. (NYSE: RP). Synercid is the first antibiotic to be indicated for the treatment of patients with serious or life-threatening infections associated with vancomycin-resistant Enterococcus faecium bacteremia. Certain strains of Enterococcus faecium have proven to be resistant to virtually all available antibiotics -- until now. Synercid is active against these strains, although several cases of emerging resistance occurred in VREF trials. The FDA also approved Synercid to treat patients with complicated skin and skin structure infections caused by methicillin-susceptible Staphylococcus aureus or Streptococcus pyogenes. One of Synercid's approved indications is for the treatment of patients with serious or life-threatening infections associated with vancomycin-resistant Enterococcus faecium (VREF) bacteremia. Synercid has been approved for marketing in the United States for this indication under FDA's accelerated approval regulations that allow marketing of products for use in life-threatening conditions when other therapies are not available. Approval of drugs for marketing under these regulations is based upon a demonstrated effect on a surrogate endpoint that is likely to predict clinical benefit. Approval of this indication is based on Synercid's ability to clear VREF from the bloodstream, with clearance of bacteremia considered to be a surrogate endpoint. There are no results from well-controlled clinical studies that confirm the validity of this surrogate marker. However, a study to verify the clinical benefit of therapy with Synercid on traditional clinical endpoints (such as cure of the underlying infection) are underway. The two distinct antibiotic agents that form Synercid, quinupristin and dalfopristin, work synergistically to inhibit or destroy susceptible bacteria through a two-pronged attack on protein synthesis in bacterial cells. Without the ability to manufacture new proteins, the bacterial cells are inactivated or die. Synercid was studied globally in comparative clinical trials for skin and skin structure infections and in non-comparative emergency use trials for VREF. The emergency-use program was established by RPR in 1993 to provide doctors, upon request, access to Synercid to treat infected patients for whom no other available drug was effective. Among the 1,222 enrolled patients, 27% did not have specific site of infections but had two or more blood cultures with pure vancomycin-resistant E. faecium. Ninety percent of these patients had clearance of their bacteremia within the first 48-72 hours of administration of Synercid. The overall efficacy rate in the patients who met strict clinical criteria (24.4% of overall patients) was 52.3 percent. Additionally, two comparative studies of complicated skin and skin structure infections were conducted. In the combined studies, the overall efficacy rate for cellulitis, post-operative infections and traumatic wound infections was 63.4%, 36.8% and 60.0%, respectively. The most common adverse drug reactions in comparative trials were inflammation at the infusion site (42.0%), and pain at the infusion site (40.0%). In three non-comparative trials, the most common adverse drug reactions were arthralgia (7.8%, 5.2%, and 4.3%), myalgia (5.1%, 0.95%, and 3.1%), both arthralgia and myalgia (7.4%; 3.3%, and 6.8%), and nausea (3.8%, 2.8%, and 4.9%). P450 3A4 substrates (e.g., cyclosporine A, midazolam, nifedipine, and terfenadine) should be used with caution and monitored when coadministered with Synercid. Those drugs used concomitantly that may prolong the QTc interval should be avoided. Rhone-Poulenc Rorer is a global pharmaceutical company dedicated to improving human health. Rhone-Poulenc S.A. (NYSE: RP) is a leading life sciences company, growing through innovations in human, plant and animal health and through its specialty chemicals subsidiary, Rhodia. With sales in 1998 of FF86.8 billion (US $14.8 billion; Euros 13.2 billion), the company employs 65,000 people in 160 countries worldwide. The RPR Internet 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 Tom Jones, 212-448-4296, or Rebecca Hamm, 212-448-4364, both of Ketchum, 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 Subscribers please note that material bearing the slug "PROTEXT" is not part of CTK's news service and is not to be published under the "CTK" slug. 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