Interim Results from a New Trial of CANCIDAS in Pediatric Patients with Documented Fungal Infections
SAN DIEGO -- CANCIDAS® (caspofungin acetate), given once daily, was evaluated as a treatment for patients three months to 17 years of age with documented or suspected fungal infections. The use of CANCIDAS in pediatric patients is investigational. Interim results from the first Phase II clinical trial to study this therapy in pediatric patients with invasive candidiasis, esophageal candidiasis or invasive aspergillosis (as salvage therapy only) will be presented on Sunday, October 7, at the 45th Annual Meeting of the Infectious Diseases Society of America (IDSA).
Preliminary data from the first 39 patients enrolled in the study found that 74 percent of trial participants treated with CANCIDAS achieved complete or significant improvement in signs and symptoms related to each infection type studied. Favorable response was determined based on complete (in the case of patients with candidemia) or significant clinical and, where appropriate, microbiological or radiographic/endoscopic improvement.
Specifically, 81 percent (22/27) of patients with invasive candidiasis, 100 percent (1/1) of patients with esophageal candidiasis and 50 percent (5/10) of patients with invasive aspergillosis had a favorable response at the end of CANCIDAS therapy. One patient (4 percent) relapsed after four weeks post-therapy. Duration of treatment was individualized for each patient, in accordance with IDSA practice guidelines. The mean duration of treatment for patients with invasive aspergillosis was 42.7 days, 12.3 days for invasive candidiasis and 32 days for esophageal candidiasis.
There were no drug-related serious adverse events and no discontinuations of CANCIDAS therapy due to toxicity. Twenty-eight percent of trial participants experienced clinical drug-related adverse events. Fever (8 percent) and rash (8 percent) were the most frequent clinical drug-related adverse events reported in >1 patient. Thirty-one percent of trial participants experienced laboratory drug-related adverse events which included increases in two liver enzymes that measure liver function – aspartate aminotransferase (18 percent) and alanine aminotransferase (10 percent); ï€ an increase in a type of white blood cell count – the eosinophil cell (5 percent); and decreases in magnesium and phosphorus levels (5 percent). However, many laboratory abnormalities had returned to prestudy levels or were decreasing by the end of therapy. One systemic infusion-related adverse event of severe intensity (thrombophlebitis) and one event of moderate intensity (fever) were also reported. There were five deaths (13 percent) reported through five weeks posttherapy, all in patients with invasive aspergillosis. None were considered by the investigator to be related to therapy with CANCIDAS.
“These interim results are a preliminary indicator that CANCIDAS may be a therapeutic intervention for pediatric patients with invasive fungal infections,†said Dr. Theoklis Zaoutis, assistant professor of Pediatrics and Epidemiology, Division of Infectious Diseases, Children's Hospital, Philadelphia, and lead study investigator.
Study design
This prospective, open-label, multi-center noncomparative study enrolled patients aged three months to 17 years of age with:
Proven or probable invasive aspergillosis refractory to or intolerant of standard antifungal therapy
Proven esophageal candidiasis (based on clinical, endoscopic and microbiological (or histopathological) criteria)
Invasive candidiasis (with clinical and microbiological evidence within 96 hours of study entry)
Study exclusion criteria included invasive aspergillosis in which the disease was limited to allergic bronchopulmonary aspergillosis (ABPA), aspergilloma, or ocular disease; Candida endocarditis, osteomyelitis, or meningitis; prosthetic device at suspected site of infection not removed within 72 hours; esophageal candidiasis limited to oropharynx and other cause of esophagitis or other esophageal pathology.
Participants were followed for 14 days post-treatment to evaluate safety and 28 days post-treatment for relapse. A total of 12 sites in five countries are enrolling patients with a target of approximately 50 participants. CANCIDAS was administered as primary or salvage therapy for esophageal candidiasis and invasive candidiasis and as salvage therapy for invasive aspergillosis. Patients were given CANCIDAS 50 mg/m2 daily (maximum 70 mg daily) following a 70 mg/m2 loading dose on day one. Patients could be dose-escalated to CANCIDAS 70 mg/m2 daily (maximum 70 mg/day) if not responding.
About fungal infections
Candidemia – a form of invasive candidiasis – is the fourth most common bloodstream infection among hospitalized patients in the United States. Invasive aspergillosis, a fungal infection that originates most commonly in the lungs, often occurs in severely immune-compromised patients and is associated with high mortality. Esophageal candidiasis is a fungal infection that forms in the esophagus and is largely caused by Candida species. It most commonly occurs in immunosuppressed patients and is among the most common opportunistic infection in patients with advanced HIV infection.
Fungal infections resulting from Candida or Aspergillus species are a significant cause of morbidity and mortality, and immunosuppressed patients such as those with persistent fever and neutropenia are at a particularly high risk. In fact, one form of fungal infection, invasive candidiasis, has a mortality rate of 40 to 60 percent with bloodstream and disseminated infection in adults.
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 in adults 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
Caspofungin is not currently approved for use in pediatric patients. CANCIDAS is contraindicated in patients with hypersensitivity to any component of the product. 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.
About Merck
Merck & Co., Inc. is a global research-driven pharmaceutical company dedicated to putting patients first. Established in 1891, Merck currently discovers, develops, manufactures and markets vaccines and medicines to address unmet medical needs. The Company devotes extensive efforts to increase access to medicines through far-reaching programmes that not only donate Merck medicines but help deliver them to the people who need them. Merck also publishes unbiased health information as a not-for-profit service. For more information, visit www.merck.com.
Forward-looking statement
This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act of 1995. These statements are based on management’s current expectations and involve risks and uncertainties, which may cause results to differ materially from those set forth in the statements. The forward-looking statements may include statements regarding product development, product potential or financial performance. No forward-looking statement can be guaranteed, and actual results may differ materially from those projected. Merck undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise. Forward-looking statements in this press release should be evaluated together with the many uncertainties that affect Merck's business, particularly those mentioned in the risk factors and cautionary statements in Item 1A of Merck's Form 10-K for the year ended Dec. 31, 2006, and in its periodic reports on Form 10-Q and Form 8-K, which the company incorporates by reference.