Single dose phase I data on CG53135 for the prevention of oral mucositis

CuraGen Corporation has announced results presented from a Phase I clinical trial with CG53135 for the prevention of oral mucositis (OM) in patients receiving high dose chemotherapy (HDCT) followed by autologous hematopoietic stem cell transplantation (AHSCT) at the ASH 46th Annual Meeting in San Diego, CA.

Results from this Phase I study suggest that CG53135 is well tolerated following intravenous administration and support the company's strategy to investigate in Phase II the safety and efficacy of a single dose of CG53135 for the prevention of oral mucositis.

"Oral mucositis is a severe side effect experienced by patients undergoing bone marrow transplants receiving high-dose chemotherapy. A drug with the ability to prevent and treat this condition has the potential to avoid complications associated with OM and improve patients' quality of life," stated Michael W. Schuster, M.D., Principal Investigator, Professor of Clinical Medicine in the Division of Hematology/Oncology at the Weill Medical College of Cornell University, and Director of Stem Cell Transplantation at NewYork-Presbyterian Hospital/Weill Cornell Medical Center. "Based on the results from this Phase I study, I look forward to investigating the efficacy of this molecule in an expanded Phase II clinical trial."

"We are very pleased with the results from this Phase I safety study and look forward to establishing the efficacy of CG53135 for the prevention of oral mucositis in our recently initiated Phase II program," stated William Hahne, M.D., Vice President of Clinical Development. "We are also excited to initiate an additional Phase I program that will evaluate the safety and potential efficacy of CG53135 for the treatment of active OM."

Data available on 22 of the 30 patients dosed to date with CG53135 were presented in a poster entitled, "Phase I Trial of CG53135-05 to Prevent Mucositis in Patients Undergoing High-Dose Chemotherapy (HDCT) and Autologous Hematopoietic Stem Cell Transplantation (AHSCT)." Primary objectives for the study were the evaluation of safety, tolerability, and pharmacokinetics following a single-dose of CG53135. As a secondary objective, the study assessed the development of OM using the WHO oral mucositis assessment scale. Patients received a single-dose of 0.03, 0.1, 0.2, or 0.33 mg/kg CG53135 administered intravenously one day after infusion of blood stem cells following high-dose chemotherapy.

Of the 22 patients (male = 17, female = 5) presented in this poster, median age was 52.5 years (range 25-75) with diagnoses including multiple myeloma (n=11), non-Hodgkin's lymphoma (n=9), acute myelogenous leukemia (n=1) and desmoplasmic round cell tumor (n=1). High-dose chemotherapy conditioning regimens included high-dose melphalan (Mel 200), carboplatin and thiotepa, cyclophosphamide, carmustine, and etoposide, and busulfan and cyclophosphamide. No drug related serious adverse events were noted following treatment with CG53135. Mild-moderate reactions including nausea, vomiting, tachycardia, hypotension, chills, and fever were observed. Infusional reactions in the two patients treated at the highest dose level were considered dose limiting. A total of 18 of 22 patients (81.8%) did not develop severe grade 3 or 4 OM. Of the 4 patients experiencing severe OM, all were treated with high dose melphalan, and the duration of grade 3 OM was brief (2-5 days) for three of these patients. Two of these patients had a prior history of developing severe OM during previous transplant. One developed brief grade 3 OM, and the other developed Grade 4 OM.

The 0.03, 0.1 and 0.2 mg/kg single doses of CG53135 are being evaluated in a randomized, double-blind, placebo-controlled, multi-center Phase II clinical trial for the prevention of OM in approximately 200 patients receiving HDCT followed by AHSCT.

CG53135, a novel fibroblast growth factor discovered by CuraGen that appears to promote both epithelial and mesenchymal cell proliferation, is currently being investigated for the prevention and treatment of OM, a side effect experienced by cancer patients undergoing chemotherapy or radiation therapy. The disease is characterized by inflammation and ulceration of the tissue lining the mouth and throat, leading to bleeding, pain, and difficulty eating and drinking. OM is sometimes a cause for clinicians to interrupt patients' cancer treatment regimens, thus limiting the success of therapeutic plans. CG53135 is being investigated for the prevention of OM by being administered to patients before the onset of symptoms in order to decrease the incidence and duration of the disease. Animal studies suggest that CG53135 may also be effective for the treatment of OM when it is administered after the onset of early signs of OM in order to decrease the duration and progression to severe OM. An effective therapy for OM has the potential to treat debilitating symptoms, to allow cancer patients to better tolerate the appropriate doses of cancer treatment, and to decrease hospitalization time.