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US Food and Drug Administration

Approval of synercid for certain vancomycin resistant infections

FDA Talk Paper (Sep) T99:44 1999

FDA
TALK PAPER

Food and Drug Administration
U.S. Department of Health and Human Services
Public Health Service 5600 Fishers Lane Rockville, MD 20857


FDA Talk Papers are prepared by the Press Office to guide FDA personnel in responding with consistency and accuracy to questions from the public on subjects of current interest. Talk Papers are subject to change as more information becomes available.


T99-44                                            Print Media:         301-
827-6242
September 21,1999                                 Broadcast Media:     301-
827-3434
                                                  Consumer Inquiries:  888-
INFO-FDA

APPROVAL OF SYNERCID FOR CERTAIN VANCOMYCIN RESISTANT INFECTIONS

FDA today approved Synercid, the first antibacterial drug to treat infections associated with vancomycin-resistant Enterococcus faecium bacteremia (VREF) when no alternative treatment is available. Synercid also received approval for complicated skin and skin structure infections. The following may be used to respond to questions.

Infections due to Enterococcus faecium are particularly known to occur in hospitalized or immunocompromised individuals. This organism is often resistant to multiple antibiotics. Vancomycin has, for many years, served as the last resort for treatment of these infections. In 1989 the first case of vancomycin-resistant Enterococcus faecium (VREF) was reported in this country. Since then, there has been a rapid increase in the incidence of VREF.

Synercid, a combination of quinupristin and dalfopristin, is the first drug in the streptogramin class approved for use in humans in the United States. The drug has been granted accelerated approval, a regulatory mechanism that allows early approval for products intended to treat serious or life- threatening conditions when they provide meaningful therapeutic benefit over existing treatments. Accelerated approval is based on surrogate markers of effectiveness, in this case, the drug's ability to clear VREF infection from the bloodstream. A study to verify the clinical benefit (e.g., resolution of the specific site of infection) of therapy with Synercid is underway.

Synercid's approval was supported by clinical trials of more than 2000 patients; 1222 patients were treated with Synercid in four non-comparative studies for treatment of VREF infections. In general, these patients were severely ill, making many of them unable to be fully evaluated for purposes of the clinical trials. For those who were able to be evaluated, based on strict study criteria, the overall effectiveness rate of Synercid was 52 percent. Sources of VREF infection included intra-abdominal sites, skin, soft tissue and the urinary tract. Additionally 330 of the enrolled VREF patients (out of the original 1222) had VREF bacteremia of unknown origin. For this subgroup, 90 percent had clearance of VREF in the first 48 to 72 hours of starting therapy.

Synercid was also found to be safe and effective for treatment of skin and soft tissue infections caused by methicillin-susceptible Staphylcoccus aureas (MSSA) and by Streptococcus pyogenes in two controlled clinical trials. In these studies 450 patients enrolled in the Synercid arms were compared with 443 patients treated with antibacterial drugs oxacillin or cefazolin.

The most frequently reported side effects attributed to Synercid in the clinical studies were muscle and joint pain, nausea, diarrhea, vomiting and rash. In studies in which the drug was administered through a peripheral vein (e.g., in the arm) many patients experienced local reactions to the injection, including pain and inflammation at the catheter injection site.

FDA's approval follows the recommendations of the Anti- Infective Drugs Advisory Committee. Their recommendation for the approval of the VREF indication was based, in addition to the results of the clinical studies, on the lack of availability of approved drugs for the treatment of this resistant infection which may be serious and life- threatening.

Rhone-Poulenc Rorer, a French company with US headquarters in Collegeville, Pa., will market Synercid in the United States.