University of Bologna; G-CSF-primed BM autografts improve hematopoietic recovery in some cancer patients
(c) Copyright 2003, Biotech Week via NewsRx.com
In a recent study, researchers in Italy "assessed the hematopoietic recovery and transplantation-related mortality (TRM) of patients who had failed peripheral blood stem cell mobilization and subsequently received high-dose chemotherapy supported by granulocyte colony-stimulating factor (G-CSF)-primed bone marrow (BM)."
The participants were "86 heavily pretreated consecutive patients with acute leukemia (n=21), refractory/relapsed non-Hodgkin lymphoma (n=41) and Hodgkin disease (n=17), and multiple myeloma (n=7)," noted R.M. Lemoli and coauthors at the University of Bologna.
"There were 78 patients who showed insufficient mobilization of CD34+ cells (<10 cells/microL), whereas eight patients collected less than 1 x 106 CD34+ cells/kg," they wrote in the journal Blood. "BM was primed in vivo for three days with 15-16 microg/kg of subcutaneous G-CSF. Median numbers of nucleated cells, colony-forming unit cells (CFU-Cs), and CD34+ cells per kilogram harvested were 3.5 x 108, 3.72 x 104, and 0.82 x 106, respectively."
"Following myeloablative chemotherapy, median times to achieve a granulocyte count higher than 0.5 x 109/L and an unsupported platelet count higher than 20 and 50 x 109/L were 13 (range, 8-24), 15 (range, 12-75), and 22 (range, 12-180) days, respectively, for lymphoma/myeloma patients and 23 (range, 13-53), 52 (range, 40-120), and 90 (range, 46-207) days, respectively, for leukemia patients," study data indicated.
"Median times to hospital discharge after transplantation were 17 (range, 12-40) and 27 (range, 14-39) days for lymphoma/myeloma and acute leukemia patients, respectively," according to the report. "TRM was 4.6%, whereas 15 patients died of disease."
"G-CSF-primed BM induces effective multilineage hematopoietic recovery after high-dose chemotherapy and can be safely used in patients with poor stem cell mobilization," the researchers concluded.
Lemoli and colleagues published their study in Blood (Autologous transplantation of granulocyte colony-stimulating factor-primed bone marrow is effective in supporting myeloablative chemotherapy in patients with hematologic malignancies and poor peripheral blood stem cell mobilization. Blood, 2003;102(5):1595-1600).
For additional information, contact R.M. Lemoli, University of Bologna, Seragnoli Institute of Hematology and Medical Oncology, Via Massarenti 9, I-40100 Bologna, Italy.
EntreMed selects Panzem formulation.
(c) 2003 Elsevier Engineering Information www.ei.org
EntreMed Inc has selected the final formulations of Panzem, EntreMed's lead drug candidate currently in Phase II oncology trials. EntreMed expects to transition the reformulated Panzem into new clinical trials in early 2004. These new formulations, all orally administered, are designed to increase the amount of Panzem that circulates in the patient's bloodstream by increasing absorption of the drug candidate. The new Panzem formulations result in circulating levels more than ten fold higher in pre-clinical animal models when compared to the existing formulation. Further, preliminary toxicity studies indicate that the newly formulated Panzem has a strong safety profile, similar to the current clinical formulation. The new Panzem formulations have been prepared using existing supplies of Panzem bulk material purchased in May 2003. This bulk material is being used to prepare GMP material for clinical trials beginning in 1Q 2004.
Panzem [2-methoxyestradiol (2ME2)] is a naturally occurring metabolite of endogenous estrogen. Its versatile properties allow a wide range of potential formulations for drug delivery to treat numerous indications. In Phase I and Phase II oncology trials, orally administered Panzem has demonstrated anticancer activity in patients with breast cancer, prostate cancer and multiple myeloma, a blood cancer. Clinical investigators reported patients have shown tumour response, stable disease and/or clinical benefit, including one patient who received Panzem in combination with Taxotere having a complete tumour response and an additional patient with ovarian cancer treated with Panzem alone who demonstrated a durable partial response. Results in pre-clinical models with ocular implants of Panzem have demonstrated that it may inhibit neovascularization of age-related macular degeneration (ARMD). Allergan and EntreMed are developing the localized use of Panzem for the treatment of ARMD and other diseases of the eye. EntreMed Inc is a clinical-stage biopharmaceutical company developing therapeutics that simultaneously target the biological pathways of angiogenesis inflammation, coagulation and/or apoptosis, pathways associated with over 80 diseases such as cancer, blindness and atherosclerosis.
NeoRx and FDA Reach Agreement on STR Phase III Registration Trial Through Special Protocol Assessment
(c) 2003 Business Wire.
NeoRx Corporation (Nasdaq:NERX), a cancer therapeutics development company, today announced that it has reached agreement with the US Food and Drug Administration (FDA), under the Special Protocol Assessment (SPA) process, on the design of the phase III clinical trial for STR(TM) (Skeletal Targeted Radiotherapy) in patients with multiple myeloma, a cancer of the bone marrow. NeoRx also confirmed with the FDA that a single phase III study is sufficient for registration of STR. The Company expects to open the trial for patient enrollment in the first quarter of 2004.
The phase III trial planned under the SPA will be a randomized, controlled study of STR in patients with primary refractory multiple myeloma. The trial is expected to enroll approximately 240 evaluable patients, half on the experimental arm and half on the control arm. Patients on the experimental arm will receive STR plus the chemotherapy drug melphalan, followed by autologous stem cell transplantation. Patients on the control arm will receive melphalan only, followed by transplantation. The FDA accepted complete response at six months post-transplant as a surrogate endpoint for the study. Acceptance of a surrogate endpoint places STR on the Accelerated Approval path.
The SPA process creates a binding written agreement between the sponsoring company and the FDA concerning pivotal trial design, clinical end points, study conduct, data analysis, and other clinical trial issues, and is intended to provide assurance that if pre-specified trial results are achieved, they may serve as the primary basis for an efficacy claim in support of a New Drug Application (NDA). Accelerated Approval is intended to make promising products for life-threatening diseases available earlier in the course of development, by allowing approval on the basis of a clinical endpoint other than patient survival.
"We are pleased that our collaborative interaction with the FDA has produced this outcome, and we look forward to beginning the phase III study. Having qualified for Accelerated Approval should appreciably shorten the clinical development timeline for STR, while the Special Protocol Assessment provides a clear path to marketing approval, if the phase III results are positive. We plan to discuss with the FDA the availability and timing of additional regulatory provisions that could further expedite the approval process for STR, including Fast Track and Priority Review," said Jack L. Bowman, CEO and Chairman.
NeoRx previously reported phase I/II results for STR plus melphalan and autologous stem cell transplantation in 83 evaluable patients with multiple myeloma, treated at various doses of STR and various doses of melphalan. Among the 83 phase I/II patients were 22 with primary refractory disease, five (23%) of whom achieved a complete response (CR) to therapy. Eight patients with primary refractory disease were treated at the 200 mg / m2 dose of melphalan that will be used in the upcoming phase III trial. All eight patients (100%) achieved disease stabilization or better, including two patients (25%) with a CR and one patient with a Very Good Partial Response (VGPR). All response assessments were made by an independent expert using rigorous, internationally accepted criteria.
"Primary refractory patients are a particularly challenging population, as they have failed to achieve a response to at least one regimen of chemotherapy. Historically, when these patients are conditioned with melphalan alone prior to transplant, the CR rate is only about 7%. In multiple myeloma, increasing the CR rate is the key to prolonging progression-free and overall patient survival. The results we have achieved to date suggest that STR can substantially increase the CR rate," said Karen Auditore-Hargreaves, PhD, Chief Operating Officer.
STR is a targeted therapeutic comprised of a small-molecule bone-seeking agent coupled to the radionuclide holmium-166. In addition to multiple myeloma, STR also may have potential for treating leukemias, lymphomas, and bone metastases of breast, prostate, and other cancers. NeoRx intends to produce STR for the phase III study at its radiopharmaceutical manufacturing facility in Denton, TX, and has begun preparations to ramp up operations at that facility.
This release contains forward-looking statements relating to the development of the Company's products and future operating results that are subject to certain risks and uncertainties which could cause actual results to differ materially from those projected. The words "believe," "expect," "intend," "anticipate," variations of such words, and similar expressions identify forward-looking statements, but their absence does not mean that the statement is not forward-looking. These statements are not guarantees of future performance and are subject to certain risks, uncertainties and assumptions that are difficult to predict. Factors that could affect the Company's actual results include conditions in the capital markets in general and in the life science sector in particular, specifically those that may affect potential financing sources for the development of NeoRx's business, the pro! gress and costs of clinical trials and the timing of regulatory approvals, the availability of clinical materials from third-party suppliers, NeoRx's ability to manufacture STR in a timely and cost-effective manner and commercialize products and other risks and uncertainties described in NeoRx's current and periodic reports filed with the Securities and Exchange Commission, including NeoRx's Annual Report on Form 10-K for the year ended December 31, 2002 and its latest Quarterly Report on Form 10-Q. Readers are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date of this release. The Company undertakes no obligation to update any forward-looking statement to reflect new information, events or circumstances after the date of this release or to reflect the occurrence of unanticipated events.