Healthcare Industry News: myelodysplastic syndromes
News Release - January 25, 2007
The New England Journal Of Medicine Publishes Two Landmark Studies Of NOXAFIL(R) (Posaconazole) in the Prevention of Invasive Fungal InfectionsKENILWORTH, N.J., Jan. 25 (HSMN NewsFeed) -- Two landmark clinical studies demonstrating the efficacy of NOXAFILŽ (posaconazole) Oral Suspension in the prevention (prophylaxis) of life-threatening invasive fungal infections (IFIs) caused by Aspergillus and Candida in high-risk patients were published today in The New England Journal of Medicine,(1,2) reported Schering-Plough Corporation (NYSE: SGP ). High-risk patients who develop IFIs have a mortality rate ranging from 50-90 percent.(3) In both these studies, NOXAFIL was significantly more effective in preventing invasive aspergillosis and reducing deaths related to invasive fungal infections, and, in one study, reducing overall mortality, versus the combined comparator drugs.
NOXAFIL is the first and only antifungal agent approved for the prevention of IFIs caused by Aspergillus.
"Prophylaxis is a commonly used therapeutic strategy, because the diagnosis of fungal infection is often delayed or difficult to establish with certainty, and a delay in antifungal treatment increases mortality," said Oliver Cornely, M.D., assistant professor, 1st Department for Internal Medicine, University of Cologne, Germany, and lead author of one of the published studies. "With posaconazole, we now can help prevent infections caused by the two most common pathogens, Aspergillus and Candida, before they occur."
More than 1,200 patients were enrolled in the studies, which demonstrated substantially fewer breakthrough Aspergillus infections with NOXAFIL prophylaxis versus the combined comparator drugs (fluconazole, itraconazole) in high-risk patients. These patients included hematopoietic stem cell transplant (HSCT) recipients with graft-versus-host disease (GVHD) or those with hematologic malignancies such as acute myelogenous leukemia (AML) or myelodysplastic syndromes (MDS) with prolonged neutropenia from chemotherapy. In high-risk neutropenic patients, NOXAFIL prophylaxis was associated with decreased all-cause mortality versus the combined comparator drugs. In these studies, NOXAFIL demonstrated an adverse event profile comparable to fluconazole.
"There is an urgent need worldwide for establishing a standard of care for preventing life-threatening fungal infections in high-risk patients. Due to an expanding patient population, these infections are being seen more frequently and are a leading cause of death in these seriously ill patients," said Andrew J. Ullmann, M.D., attending physician for infectious diseases and hematology/oncology, 3rd Medical Department of the University Hospital of the Johannes Gutenberg University, Mainz, Germany, and lead author of one of the published studies. "These studies demonstrate that posaconazole prophylaxis provides effective, well-tolerated, preventive therapy, allowing physicians to focus on treating their patient's underlying disease."
About the Published Studies
Posaconazole vs. Fluconazole or Itraconazole Prophylaxis in Patients with Neutropenia (Cornely et al.): This randomized, multicenter, open-label study compared NOXAFIL Oral Suspension 200 mg three times daily (n=304) to fluconazole oral suspension 400 mg once daily (n=240) or itraconazole oral solution 200 mg twice daily (n=58) as prophylaxis against IFIs in neutropenic patients who were receiving cytotoxic chemotherapy for AML or MDS. In this study, NOXAFIL versus fluconazole/itraconazole demonstrated a reduction in proven and probable IFIs, the primary study endpoint (2 percent vs. 8 percent); significantly fewer breakthrough Aspergillus infections (1 percent vs. 7 percent); and improved overall survival.
Posaconazole or Fluconazole for Prophylaxis in Severe Graft-versus-Host Disease (Ullmann et al.): This randomized, multicenter, double-blind study compared NOXAFIL Oral Suspension 200 mg three times daily (n=301) to fluconazole capsules 400 mg once daily (n=299) as prophylaxis against IFIs in allogeneic hematopoietic stem cell transplant (HSCT) recipients with graft- versus-host disease (GVHD). At the end of the fixed 112-day treatment period, NOXAFIL versus fluconazole demonstrated a reduction in proven/probable IFIs, the primary study endpoint (5 percent vs. 9 percent); a significant reduction in breakthrough Aspergillus infections (2 percent vs. 7 percent); and decreased IFI-related mortality.
NOXAFIL received marketing approval for prophylaxis in the United States and European Union (EU) in 2006, based primarily on the results of these two studies. NOXAFIL also was approved in the United States and EU in 2006 for the treatment of oropharyngeal candidiasis (OPC), a fungal infection of the mouth and throat, and in the EU in 2005 and Australia in 2006 for the treatment of certain IFIs in adult patients with disease that is refractory to or in patients who are intolerant of certain commonly used antifungal agents. NOXAFIL is a novel triazole antifungal agent discovered and developed by Schering-Plough Research Institute.
NOXAFIL Safety Information
The most common treatment-related serious adverse events (1 percent each) in the combined NOXAFIL prophylaxis studies were bilirubinemia, increased hepatic enzymes, hepatocellular damage, nausea, and vomiting. In clinical trials, there were infrequent cases of hepatic reactions (e.g., mild to moderate elevations in ALT, AST, alkaline phosphatase, total bilirubin, and/or clinical hepatitis). Rarely, more severe hepatic reactions including cholestasis or hepatic failure including fatalities were reported in patients with serious underlying medical conditions (e.g., hematologic malignancies) during treatment with NOXAFIL. Liver function tests (LFTs) should be monitored at the start of and during the course of therapy.
In the pooled prophylaxis safety analysis, fever, headache, anemia, diarrhea, nausea, vomiting, abdominal pain, hypokalemia and thrombocytopenia were frequently reported treatment-emergent adverse events.
NOXAFIL has been shown to interact with several medications, including drugs that suppress the immune system, and these reactions may be serious. The product label should be consulted when other drugs are prescribed with NOXAFIL.
In clinical studies of oropharyngeal candidiasis (OPC) and refractory OPC, adverse events were reported more frequently in the pool of patients with refractory oropharyngeal candidiasis. The most commonly reported serious adverse events included fever (13 percent) and neutropenia (10 percent).
Co-administration with the CYP3A4 substrates terfenadine, astemizole, cisapride, pimozide, halofantrine or quinidine, is contraindicated since this may result in increased plasma concentrations of these medicinal products, leading to QTc prolongation and rare occurrences of torsades de pointes. Co- administration with ergot alkaloids is also contraindicated.
Serious and rare fatal toxicity from cyclosporine has occurred when taken in combination with NOXAFIL and therefore reduction of the dose of drugs like cyclosporine, tacrolimus, or sirolimus and frequent monitoring of drug levels of these medications is necessary when taking them in combination with NOXAFIL.
The safety and effectiveness of NOXAFIL in patients below the age of 13 years old have not been established. In the EU, NOXAFIL is recommended for use in patients 18 years of age and older.
For NOXAFIL U.S. Prescribing Information please visit: http://www.spfiles.com/pinoxafil.pdf.
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 32,000 people around the world. The company is based in Kenilworth, N.J., and its Web site is www.schering-plough.com.
SCHERING-PLOUGH DISCLOSURE NOTICE: The information in this press release includes certain "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995, including statements related to the potential of NOXAFIL. Forward-looking statements relate to expectations or forecasts of future events. Schering-Plough does not assume the obligation to update any forward-looking statement. Many factors could cause actual results to differ materially from Schering-Plough's forward- looking statements, including market forces, economic factors, product availability, patent and other intellectual property protection, current and future branded, generic or over-the-counter competition, the regulatory process, and any developments following regulatory approval, among other uncertainties. For further details about these and other factors that may impact the forward-looking statements, see Schering-Plough's Securities and Exchange Commission filings, including Item 1A. Risk Factors in the Company's second quarter 2006 10-Q.
(1) Ullmann AJ, Lipton JH, Vesole DH, et al. Posaconazole or Fluconazole for Prophylaxis in Severe Graft-versus-Host Disease. N Engl J Med 2007;356:335-47.
(2) Cornely OA, Maertens J, Winston DJ, et al. Posaconazole vs. Fluconazole or Itraconazole Prophylaxis in Patients with Neutropenia. N Engl J Med 2007;356:348-59.
(3) Bow EJ, Laverdiere M, Lussier N, et al. Antifungal Prophylaxis for Severely Neutropenic Chemotherapy Recipients. Cancer 2002;94:3230-46.
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