Study Presented on Use of CANCIDAS® (caspofungin acetate) as Empirical Therapy of Suspected Invasive Fungal Infections in Pediatric Patients with Persistent Fever and Neutropenia

CANCIDAS® (caspofungin acetate) had a safety and efficacy profile generally similar to AmBisome® (liposomal amphotericin B or L-AmB) in a clinical study involving its investigational use for pediatric empirical therapy against suspected invasive fungal infections (IFI) in patients two to 17 years of age with persistent fever and neutropenia. L-AmB is regarded as a standard treatment option against IFI; and the use of CANCIDAS in pediatric patients is investigational. These results were presented today at the American Society for Microbiology’s 47th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC).

This study is the first prospective, double-blind study to assess the safety and efficacy of CANCIDAS in pediatric patients. The study assessed the safety and efficacy profile of CANCIDAS versus L-AmB when used as empirical therapy for suspected fungal infections in patients with persistent fever and neutropenia (seriously ill patients with persistent fever and low white blood cell counts). The primary endpoint of the study was the proportion of CANCIDAS-treated patients with more than one drug-related adverse event during the study period and 14 days post-therapy. The secondary endpoints of the study were drug-related serious adverse events, discontinuation due to drug-related adverse events and proportion of patients with a favorable overall efficacy outcome based on a five-part composite endpoint.

In the study, which enrolled 82 patients two to 17 years of age, CANCIDAS had a safety profile in pediatric patients generally similar to the safety profile of L-AmB in such population. In patients treated with CANCIDAS, the most common drug-related adverse events were fever (29 percent), headache (nine percent), rash (nine percent), decreased potassium (four percent), chills (two percent), rapid heart beat (two percent) and vomiting (two percent). The incidence of clinical drug-related adverse events was similar in the two groups, at a rate of 48 percent in the CANCIDAS group and 46 percent in the L-AmB group. The incidence of drug-related serious adverse events was low in the two groups, at a rate of two percent in the CANCIDAS group and 11 percent in the L-AmB group. The incidence of drug-related laboratory adverse events was also similar in the two groups, at a rate of 11 percent in the CANCIDAS group and 19 percent in the L-AMB group. There were no serious laboratory adverse events in either group.

From an efficacy perspective, patients treated with CANCIDAS achieved an overall response rate that was generally similar to L-AmB. Approximately 41 percent of patients responded favorably to CANCIDAS versus 28 percent of patients treated with L-AmB. Ninety-one percent of patients completed CANCIDAS without any premature discontinuations due to lack of efficacy or toxicity, as compared to 84 percent of patients on L-AmB. The number of patients who reported fever resolution during period of neutropenia was also similar in the two groups: 43 percent of patients treated with CANCIDAS versus 32 percent of patients on L-AmB. All patients on CANCIDAS and L-AmB survived seven days post-therapy.

“Randomized studies related to empiric therapies can be challenging to conduct in the pediatric setting,” said Johan Maertens, M.D., Chairman of the EORTC (European Organization for Research and Treatment of Cancer) Infectious Disease Group, and head of the Department of Hematology and Acute Leukemia and Transplantation Unit, University Hospital Gasthuisberg, Leuven, Belgium. “This study represents an important step forward as it provides the first look at data on the safety and efficacy on the investigational use of CANCIDAS as empiric therapy in pediatric patients.”

IFI lead to considerable morbidity and mortality, and can be life threatening in neutropenic patients who receive chemotherapy for cancer or have immunocompromising conditions. Empirical therapy - or the treatment of suspected fungal infections - for patients with persistent fever and neutropenia has become universally accepted as a standard approach due to the relative insensitivity of diagnostic methods.

Study design
These findings were from a randomized, double-blind, multi-center, comparative trial involving a total of 82 patients aged two to 17 years of age with persistent fever and neutropenia. The patients were enrolled at 17 clinical trial sites across four countries (Belgium, Germany, Spain and the United States). The trial was designed to evaluate the safety of CANCIDAS versus L-AmB based on the presence of clinical or laboratory adverse events. Efficacy was also evaluated using a five-part composite endpoint comprised of survival to seven days post-therapy, successful treatment of baseline IFI, prevention of breakthrough IFI up to seven days post-therapy, no premature discontinuation due to lack of efficacy or drug toxicity, and fever resolution for 48 hours during the period of neutropenia.

Patients were randomized using a 2:1 CANCIDAS: L-AmB ratio and were given either CANCIDAS 50 mg/m² daily (maximum 70 mg daily) following a 70 mg/m² loading dose on day 1 or L-AmB 3 mg/kg daily. Patients could be dose-escalated after five days to CANCIDAS 70 mg/m² (maximum 70 mg daily) or L-AmB 5 mg/kg daily. The total duration of the study was 29 months.

About CANCIDAS
CANCIDAS is a member of the echinocandin class of antifungals. CANCIDAS inhibits the synthesis of β(1,3)-D-glucan, an integral component of the fungal cell wall. CANCIDAS is administered via intravenous infusion.

In the United States, CANCIDAS is indicated for:

* Empirical therapy for presumed fungal infections in febrile, neutropenic patients
* Treatment of candidemia and the following Candida infections: intraabdominal abscesses, peritonitis, and pleural space infections; CANCIDAS has not been studied in endocarditis, osteomyelitis, or meningitis due to Candida
* Treatment of esophageal candidiasis
* Treatment of invasive aspergillosis in patients who are refractory to or intolerant of other therapies

Selected important risk information about CANCIDAS
CANCIDAS is contraindicated in patients with hypersensitivity to any component of the product. Safety and effectiveness has not been established in pediatric patients. Concomitant use of CANCIDAS with cyclosporine should be limited to patients for whom the potential benefit outweighs the potential risk of increased hepatic enzyme abnormalities.

Laboratory abnormalities in liver function tests have been seen in healthy volunteers and patients treated with CANCIDAS. In some patients with serious underlying conditions who are receiving multiple concomitant medications along with CANCIDAS, clinical hepatic abnormalities have also occurred. Isolated cases of significant hepatic dysfunction, hepatitis, or worsening hepatic failure have been reported in patients; a causal relationship to CANCIDAS has not been established. Patients who develop abnormal liver function tests during therapy with CANCIDAS should be monitored for evidence of worsening hepatic function and evaluated for risk/benefit of continuing therapy with CANCIDAS.

Possible histamine mediated symptoms have been reported including rash, facial swelling, pruritus, sensation of warmth and bronchospasm. Anaphylaxis has been reported during administration of CANCIDAS.

For details about CANCIDAS, please read the accompanying prescribing information.