Schering-Plough Announces FDA Approval of AVELOX(R) (moxifloxacin HCl) for Treatment of Complicated Skin and Skin Structure Infections

KENILWORTH, N.J., June 30 /PRNewswire/ -- Schering-Plough Corporation today announced that the U.S. Food and Drug Administration (FDA) has approved the once-daily antibiotic AVELOX(R) (moxifloxacin HCl) for the treatment of complicated skin and skin structure infections (cSSSI) in adults caused by methicillin-susceptible Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae or Enterobacter cloacae. AVELOX was developed by Bayer Pharmaceuticals Corporation and is marketed in the United States by Schering- Plough.

There are 2.5 million cSSSI cases in the U.S. annually, with approximately 400,000 patients requiring hospitalization.(1) Treatment of these infections typically involve high doses of antibiotics, often requiring multiple doses per day.

"Complicated skin and skin structure infections can be severe and may require surgery to resolve," said Ellie J.C. Goldstein, M.D., director of the R.M. Alden Research Laboratory, Santa Monica, Calif. and clinical professor of medicine at David Geffen School of Medicine at UCLA, Los Angeles, Calif. "Since AVELOX features once-a-day administration, it offers a convenient and effective treatment option for patients," he said.

"This new indication for AVELOX represents a meaningful alternative treatment approach for patients and an important new offering for Schering- Plough's anti-infectives portfolio," said Robert J. Spiegel, M.D., chief medical officer and senior vice president of medical affairs, Schering-Plough Research Institute.

Schering-Plough acquired exclusive U.S. rights to market, sell and distribute Bayer's fluoroquinolone antibiotics AVELOX and CIPRO(R) (ciprofloxacin) in October 2004. As holder of the New Drug Application (NDA) and patents for AVELOX, Bayer completed the research and FDA submission related to this new indication.

In the studies on which the FDA approval was based, sequential intravenous or oral monotherapy with AVELOX once daily for cSSSI patients demonstrated similar efficacy to IV piperacillin-tazobactam four times daily followed by oral amoxicillin-clavulanate twice daily.

The FDA approval to treat cSSSI is the fifth indication for AVELOX, which is currently approved in the United States to treat acute bacterial sinusitis (ABS), acute bacterial exacerbation of chronic bronchitis (ABECB), community acquired pneumonia (CAP) and uncomplicated skin and skin structure infections (uSSSI).

AVELOX Studies in cSSSI

Two randomized, active controlled trials in cSSSI were performed. A double-blind, prospective, multicenter trial was conducted primarily in North America to compare the efficacy of sequential intravenous (IV) or oral (PO) monotherapy with AVELOX 400 mg once daily (QD) for 7-14 days to an IV/PO beta-lactam/beta-lactamase inhibitor control in the treatment of patients with cSSSI. This study enrolled 617 patients, of which 335 were valid for the primary efficacy analysis. Infections observed in both patient groups included abscess, cellulitis, ischemic/decubitus ulcer, surgical wound infection and traumatic lesion. A second open-label international study compared AVELOX 400 mg QD for 7-21 days to sequential IV/PO beta-lactam/beta- lactamase inhibitor control in the treatment of patients with cSSSI. This study enrolled 804 patients, 632 of which were valid for primary efficacy analysis.

In the North American trial, the overall success rates in evaluable patients for AVELOX versus the comparator were 77.2 percent and 81.5 percent, respectively. In this study, AVELOX demonstrated similar efficacy to the comparator, 82.2 percent and 87.6 percent, respectively, in eradicating methicillin-susceptible strains of Staphylococcus aureus, one of the key pathogens that cause cSSSI. Pooled clinical success rates by pathogen in the North American and international trials for AVELOX versus the comparator, respectively, were 81.6 percent and 84.8 percent for E. coli; 91.7 percent and 70 percent for K. pneumoniae; and 81.8 percent versus 57.1 percent for E. cloacae.

About Complicated Skin and Skin Structure Infections (cSSSI)

Broad categories of skin and skin structure infections (e.g., superficial skin infections, cellulitis and simple abscesses) tend to share common bacterial causes. Skin and skin structure infections that are diagnosed as complicated involve deeper soft tissue (e.g., muscle, fat), may require significant surgical intervention to resolve (e.g., infected ulcers, burns, major abscesses) or are associated with an underlying disease state that complicates response to treatment. The possible bacterial causes of cSSSI are numerous and depend on the clinical situation, the location of the lesion or infection, and past medical history of the individual patient.(2)

About AVELOX

AVELOX is approved to treat: Acute Bacterial Exacerbations of Chronic Bronchitis (ABECB) caused by Streptococcus pneumoniae, Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, Staphylococcus aureus, or Moraxella catarrhalis; Acute Bacterial Sinusitis (ABS) caused by Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis; Community Acquired Pneumonia (CAP) caused by Streptococcus pneumoniae (including multi- drug resistant strains*), Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus, Klebsiella pneumoniae, Mycoplasma pneumoniae, or Chlamydia pneumoniae; Uncomplicated Skin and Skin Structure Infections (uSSSI) caused by Staphylococcus aureus or Streptococcus pyogenes; and Complicated Skin and Skin Structure Infections (cSSSI) caused by methicillin susceptible Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, or Enterobacter cloacae.

*MDRSP, Multi-drug resistant Streptococcus pneumoniae, includes isolates previously known as PRSP (penicillin-resistant Streptococcus pneumoniae), and are strains resistant to two or more of the following antibiotic classes: penicillin (MIC equal to or greater than 2 mcg/mL), second generation cephalosporins, e.g. cefuroxime, macrolides, tetracyclines and trimethoprim/ sulfamethoxazole.

SAFETY INFORMATION about AVELOX

AVELOX is generally well tolerated, with adverse events being similar to standard therapy. The most common side effects caused by AVELOX, which are usually mild, include dizziness, nausea and diarrhea. Patients should be careful about driving or operating machinery until they are sure that AVELOX is not causing dizziness. Patients should inform a health care professional of other side effects.

Patients who have ever had an allergic reaction to AVELOX or any of the other group of antibiotics known as "quinolones," such as ciprofloxacin or levofloxacin should avoid taking AVELOX.

Patients who have been diagnosed with an abnormal heartbeat such as an arrhythmia or are using certain medications used to treat an abnormal heartbeat should avoid taking AVELOX. These medications include quinidine, procainamide, amiodarone, and sotalol.

AVELOX is not for use during pregnancy or nursing, as the effects on the unborn child or nursing infant are unknown. AVELOX is not for children under the age of 18 years.

Convulsions have been reported in patients receiving quinolone antibiotics. Patients should be sure to let their physician know if they have a history of convulsions.

Many antacids and multivitamins may interfere with the absorption of AVELOX and may prevent it from working properly. Patients should take AVELOX either 4 hours before or 8 hours after taking these products.

Please see full prescribing information for AVELOX available at http://www.aveloxusa.com/.

Schering-Plough is a global science-based health care company with leading prescription, consumer and animal health products. Through internal research and collaborations with partners, Schering-Plough discovers, develops, manufactures and markets advanced drug therapies to meet important medical needs. Schering-Plough's vision is to earn the trust of the physicians, patients and customers served by its more than 30,000 people around the world. The company's Web site is http://www.schering-plough.com/.

SCHERING-PLOUGH DISCLOSURE NOTICE:

This press release contains "forward-looking statements" within the meaning of the Securities Litigation Reform Act of 1995, related to the market for AVELOX and the market for drugs to treat complicated skin and skin structure infections. Forward-looking statements relate to expectations or forecasts of future events and not to historical information. Schering-Plough does not assume the obligation to update any forward-looking statement. There are no guarantees about the market performance of AVELOX, Schering-Plough stock or Schering-Plough's business. Actual results may vary materially from Schering-Plough's forward-looking statements due to many factors and uncertainties, which include the market acceptance of AVELOX, trade buying patterns, the introduction and performance of competitive products in the market, legislation that may impact the pricing/availability of AVELOX and other items. For further details about these factors and other risks and uncertainties that may impact Schering-Plough's forward-looking statements, see Schering-Plough's Securities and Exchange Commission filings, including the company's first quarter 2005 10-Q.

References: 1. InterMune. Complicated Skin and Skin Structure Infections. Available at http://www.intermune.com/wt/itmn/oritavancin_cssi. Accessed on June 17, 2005. 2. U.S. Food and Drug Administration (FDA). Guidance for Industry: Uncomplicated and Complicated Skin and Skin Structure Infections -- Developing Antimicrobial Drugs for Treatment. Available at http://www.fda.gov/cder/guidance/2566dft.pdf. Accessed on June 15, 2005.

AVELOX is a registered trademark of Bayer AG and is used under license by Schering-Plough.