Optimer Pharmaceuticals, Inc. announced the presentation of results from a post-hoc subgroup analysis of the company's two large Phase 3 trials which demonstrated that cancer patients with Clostridium difficile-associated diarrhea (CDAD) had higher clinical cure rates, better sustained response and lower recurrence when treated with DIFICID® (fidaxomicin) tablets compared to oral vancomycin. The data will be presented at the 22nd European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) in London.
The analysis included 153 patients with active cancer who were treated in the two DIFICID Phase 3 studies and who received 8 days or more of treatment with DIFICID or oral vancomycin. In the overall combined population, patients with cancer had significantly lower cure and sustained response rates than patients without cancer. DIFICID 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, DIFICID 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). Furthermore, cancer patients who were treated with DIFICID in the clinical studies had similar cure, recurrence and sustained response rates as non-cancer patients who received the drug, while cancer patients treated with vancomycin tended to have poorer outcomes than non-cancer patients. The overall safety profile was similar between the DIFICID and vancomycin treatment groups.
"CDAD is a common, but very serious complication for cancer patients and is a growing problem nationwide," said Roy F. Chemaly, M.D., M.P.H., F.A.C.P., F.I.D.S.A., associate professor and director of Infection Control in the Department of Infectious Diseases at The University of Texas MD Anderson Cancer Center in Houston, TX. "Because CDAD can have profound and disruptive effects in cancer patients, it is important that patients achieve both an initial cure and a sustained clinical response lasting beyond the initial treatment period."
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. They also are at risk 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.
"The results from this analysis reinforce the important role of DIFICID in the treatment of CDAD, especially its use as a front-line agent," said Sherwood L. Gorbach, M.D., Chief Scientific Officer and Senior Vice President of Optimer Pharmaceuticals, Inc. "We are encouraged by these results and look forward to conducting future clinical trials to explore the potential benefits of DIFICID in patients with cancer and others who are at high risk for CDAD."
About the StudyThe results are based on two randomized, double-blind, non-inferiority Phase 3 trials conducted at sites in North America and Europe. Subjects with confirmed CDAD received either 200 mg DIFICID (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 DIFICID versus a 10-day course of vancomycin for the treatment of CDAD in adults. These studies served as the basis of approval for DIFICID by the U.S. Food and Drug Administration (FDA) in May 2011.
The subgroup analysis evaluated the treatment of 183 CDAD patients with active cancer - 153 of whom received 8 days or more of treatment - compared to 922 CDAD patients without cancer who were among the modified intent to treat population of the Phase 3 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. Clinical endpoints assessed in the 153 patients, included clinical cure at the end of treatment, recurrence of CDAD after clinical cure during the four week follow-up, and sustained clinical response (clinical cure with no recurrence in the four-week follow-up period).