A subpopulation analysis of data from two phase III studies shows that?fidaxomicin (Dificid?,?Optimer Pharmaceuticals, Inc.)tablets offered faster diarrheal symptom improvement than oral vancomycin in patients with cancer being treated for clostridium difficile-associated diarrhea or CDAD.
The results, to be presented on June 2nd during the 2012 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, IL., showed that these patients experienced resolution of their diarrheal symptoms approximately two days faster than those treated with oral vancomycin.
These results are based on two randomized, double-blind, non-inferiority Phase III trials conducted at sites in North America and Europe. Subjects with confirmed CDAD received either 200 mg fidaxomicin dosed orally twice daily or 125 mg vancomycin dosed orally four times daily for 10 days. The primary objective of the trials was to compare the safety and efficacy of a 10-day course of fidaxomicin versus a 10-day course of vancomycin for the treatment of CDAD in adults. These studies served as the basis of approval for fidaxomicin by the U.S. Food and Drug Administration (FDA) in May 2011.
?Fidaxomicin is the first antibacterial drug indicated for Clostridium difficile-associated diarrhea (CDAD) to be approved in more than 25 years. It is indicated for the treatment of CDAD in adults 18 years of age or older. Fidaxomicin is administered in 200 mg tablets given orally twice daily
?The subpopulation analysis evaluated the treatment of 183 CDAD patients with active cancer compared to 922 CDAD patients without cancer who were among the modified intent to treat population of the Phase III studies (N=1105). To be included in the analysis, patients must have had a current diagnosis of cancer at the time of CDAD diagnosis and were receiving various forms of treatment. Patients with active cancer (solid tumor or hematologic malignancy) were identified from medical history, concomitant medication indications, and adverse event entries in the case report forms. The analysis assessed the number of unformed bowel movements (UBM) per 24 hours to determine time to resolution of diarrhea (TTROD) ? defined as the duration of passing UBMs following initial treatment, with an active response considered as <3 UBM/24 hours. TTROD was defined as hours from first dose of treatment to last UBM on the day preceding two days of <3 UBM/24 hours.
?A serious complication
Infections caused by C. difficile and the resulting CDAD pose a significant threat to cancer patients, primarily those with compromised immune systems due to chemotherapy or stem cell transplants. Cancer patients also are at risk for CDAD due to prolonged hospitalization and exposure to antibiotics. In fact, cancer patients with solid tumor or hematologic malignancies account for 16% of hospital CDAD cases.
Clostridium difficile-associated diarrhea (CDAD) has become a significant medical problem in hospitals, long-term care facilities and in the community. CDAD is a serious illness resulting from infection of the inner lining of the colon by C. difficile bacteria, which produce toxins that cause inflammation of the colon, severe diarrhea and, in the most serious cases, death. Patients typically develop CDAD from the use of broad-spectrum antibiotics that disrupt normal gastrointestinal (gut) flora, possibly allowing C. difficile bacteria to flourish. Older patients in particular are at risk for CDAD, potentially because of a weakened immune system or the presence of underlying disease. Approximately two-thirds of CDAD patients are 65 years of age or older. Historically, approximately 20% to 30% of CDAD patients who initially respond to treatment experience a clinical recurrence.
?”CDAD is a serious complication for cancer patients and potentially can disrupt the effects of cancer treatment and result in dehydration, impaired functioning, fatigue and, in severe cases, death,” said Kathleen Mullane, D.O., Associate Professor of Medicine, Section of Infectious Diseases and Global Health, at the University of Chicago. “The results of this analysis indicate fidaxomicin may provide faster resolution of diarrhea when compared to vancomycin in a subset of cancer patients. While further studies are needed to confirm these findings, the results suggest the drug may serve as an important treatment option for this population and others at heightened risk for CDAD.”
“Fast resolution of diarrhea is critically important for patients undergoing cancer treatment to help resume focus on their primary cancer treatment as quickly as possible,” said Sherwood L. Gorbach, M.D., Chief Scientific Officer and Senior Vice President of Optimer Pharmaceuticals, Inc. “These results further support the strong efficacy profile of fidaxomicin.”
?Trial and analysis
The analysis assessed treatment outcomes between patients with active cancer and patients without cancer who were treated with either fidaxomicin or oral vancomycin in two large, pivotal, Phase III studies. Results showed that overall, cancer patients with CDAD had slower time to resolution of diarrhea (TTROD) than non-cancer patients (100 hours vs. 55 hours, respectively; K-M log rank p<0.001). However, when treatment outcomes were compared between cancer patients receiving fidaxomicin or oral vancomcyin, patients treated with fidaxomicin experienced resolution of diarrhea two days faster than those treated with vancomycin (74 hours vs. 123 hours, respectively; K-M log rank p=0.045). The overall safety profile was similar between the fidaxomicin and vancomycin treatment groups.
Additional results from the retrospective subpopulation analysis that demonstrate the effectiveness of fidaxomicin in treating CDAD in cancer patients recently were presented at the 22nd European Congress of Clinical Microbiology and Infectious Diseases (ECCMID). These results showed that fidaxomicin was five times more likely than vancomycin to produce a clinical response and three times more likely to lead to a sustained response, while patients treated with vancomycin had a 2.6 fold greater risk of experiencing recurrence. Specifically, fidaxomicin provided superior response compared to vancomycin across all clinical endpoints studied: clinical response (97.3% vs. 87.5%, 95% CI 1.07-23.98; p=0.041), sustained response (83.6% vs. 61.3%, 95% CI 1.50-6.91; p=0.003) and disease recurrence (14.1% vs. 30.0%, 95% CI 0.16-0.89; p=0.025).
?For more information:
– NCT01552668 – Fidaxomicin to Prevent Clostridium Difficile Colonization
– NCT01591863 – Safety, Tolerability, and Pharmacokinetics of Fidaxomicin in Pediatric Subjects With Clostridium Difficile-associated Diarrhea (CDAD)
– NCT00314951 – Fidaxomicin Versus Vancomycin for the Treatment of Clostridium Difficile-Associated Diarrhea (CDAD)
– NCT01533844 – To Determine the Feasibility of a Fidaxomicin Study in Neonates and to Assess C. Difficile (Clostridium Difficile) Involvement in the Pathogenesis (DAISY)
– NCT00468728 – PAR-101/OPT-80 Versus Vancomycin for the Treatment of Clostridium Difficile-Associated Diarrhea (CDAD)