Washington Editor

Ciphergen Biosystems Inc. saw its stock rise following the presentation of data at this week's American Society of Hematology meeting suggesting that proteomic analysis of circulating platelets can potentially be useful for early cancer diagnosis.

The Fremont, Calif.-based company's stock (NASDAQ:CIPH) gained 31.6 percent Tuesday, or $1.05, to close at $4.37. Its scientists and collaborators at the Children's Hospital Boston reported their findings at the San Diego gathering, detailing their use of Ciphergen's SELDI-TOF-mass spectrometry technology for platelet extracts to discover that a novel property of platelets detects human cancers of a microscopic size undetectable by any available diagnostic method. The platelet angiogenic profile is more inclusive than a single biomarker, because it can detect a wide range of tumor types and tumor sizes, they said, adding that relative changes in the platelet angiogenic profile permit the tracking of a tumor throughout its development, beginning from an early in situ cancer.

Platelets from mice bearing microscopic, clinically undetectable tumors of human liposarcoma were compared to tumor-free mice using Ciphergen's SELDI-TOF-MS-based ProteinChip Biomarker System and Arrays. The proteomic profiling of platelets at different stages of tumor growth resulted in increased amounts of angiogenic regulatory proteins such as VEGF, bFGF, PDGF, PF4, endostatin and tumstatin in platelets, but not in plasma. The study also confirmed that such regulatory proteins can be taken up by platelets in a selective and quantifiable manner even when a source as small as a 100 microliter Matrigel pellet is implanted subcutaneously.

In other news from the meeting:

Affymax Inc., of Palo Alto, Calif., said preclinical data showed that its lead product, Hematide, had an effect on red blood cell production. Also, pharmacokinetic studies in several different animal models demonstrated the compound's extended plasma half-life. Hematide, a peptide-based erythropoiesis-stimulating agent, is in a Phase I trial investigating its safety, pharmacokinetics and effect on reticulocytes and hemoglobin. It is being developed for anemia in patients with chronic kidney disease and cancer.

Alexion Pharmaceuticals Inc., of Cheshire, Conn., said cumulative results of an ongoing extension study showed that eculizumab administration for two years was associated with statistically significant reductions in hemolysis and the need for blood transfusions, a key clinical objective of the trial in patients with paroxysmal nocturnal hemoglobinuria. Treatment with eculizumab alone, or in combination with erythropoeitin, in aplastic patients has rendered seven of the 11 participating patients transfusion-independent for at least the last six months of the study. Also, classic symptoms attributed to hemoglobin release during red blood cell destruction, including abdominal pain, dysphagia and erectile dysfunction, have resolved or at least declined in all patients.

AnorMED Inc., of Vancouver, British Columbia, said preliminary results support the use of AMD3100 as a single agent to mobilize stem cells from healthy donors for allogeneic stem cell transplantation in cancer patients. Additional data show that AMD3100, in combination with standard stem cell mobilization regimens, provides a rapid increase in the number of peripheral blood stem cells capable of engraftment; increases the proportion of patients reaching a peripheral blood stem cell target required for transplant, even in heavily pre-treated patients; and reduces the number of apheresis sessions required for patients to reach a target number of peripheral blood stem cells.

BioCryst Pharmaceuticals Inc., of Birmingham, Ala., said Phase I/II results showed that the use of forodesine HCl was well tolerated in all 15 patients with various hematological malignancies. Seven of the 15, including two with T-cell malignancies and five with B-cell acute lymphoblastic leukemia, demonstrated a hematological benefit defined as a decrease in tumor burden. Two patients also showed normalization of bone marrow precursor elements. Separately, results from a Phase I trial demonstrated that nine of 13 cutaneous T-cell lymphoma patients showed improvement in skin and/or a pharmacodynamic response as measured by a decrease in the absolute Sezary cell numbers and/or the CD4/CD8 ratio.

Biogen Idec Inc., of Cambridge, Mass., reported new data on Zevalin (ibritumomab tiuxetan), including positive results from an open-label, multicenter Phase II study in older patients with relapsed or refractory diffuse large B-cell lymphoma. A 44 percent overall response rate to Zevalin was observed in the 103-patient study, including those previously treated with chemotherapy with or without rituximab. The best response, 58 percent, was observed in patients whose lymphoma progressed more than a year after initially presenting with the disease. Other data included findings on Zevalin's front-line use in patients diagnosed with follicular lymphoma, as well as updated results from an ongoing trial in relapsed mantle-cell lymphoma patients.

Celgene Corp., of Warren, N.J., said Phase II findings showed that Revlimid (lenalidomide) in combination with dexamethasone proved a positive therapeutic approach for newly diagnosed multiple myeloma patients. Twenty-five of 30 patients achieved an objective response, yielding a response rate of 83 percent, and 10 (33 percent) have experienced Grade 3 non-hematologic adverse events. Separately, final Phase III results from a study conducted by the Eastern Cooperative Oncology Group suggested that thalidomide might be useful in fighting myeloma both during initial treatment and as maintenance therapy. Data revealed a statistically significant difference in response rates of 63 percent vs. 41 percent (p=0.002) at four months with thalidomide plus dexamethasone compared to dexamethasone alone. Celgene said it plans to submit the data next quarter to the FDA to support a potential accelerated approval of the supplemental new drug application for Thalomid. In findings from another multiple myeloma study, Celgene said there was a statistically significant difference in event-free survival of 25.2 months vs. 13.7 months (p<0.001) after a minimum of six months of treatment with melphalan, prednisone and thalidomide vs. melphalan and prednisone alone.

Cell Genesys Inc., of South San Francisco, reported follow-up data from an ongoing Phase II trial of GVAX cancer vaccine for acute myelogenous leukemia. Patients with newly diagnosed leukemia were treated with chemotherapy, and if responsive, received autologous bone marrow stem cell transplantation and GVAX leukemia vaccine. Findings indicate that the therapy is well tolerated and might reduce residual leukemic cells that persist after chemotherapy as indicated by decreased levels of WT-1, a leukemia-associated genetic marker that is detectable in more than 95 percent of patients with active acute myelogenous leukemia.

CHU, of Poitiers, France, reported results showing that newly diagnosed patients with chronic myeloid leukemia who are treated early with imatinib (Gleevec, Novartis AG) are more likely to achieve complete cytogenetic responses and have improved long-term outcomes. Responses to imatinib were shown to be durable at 42 months.

Cyclacel Group plc, of Dundee, UK, said seliciclib (CYC202 or R-roscovitine) killed multiple myeloma cancer cells through apoptosis. Researchers at Dana-Farber Cancer Institute and Harvard Medical School, both in Boston, reported that seliciclib had potent cytotoxic effects against nine different multiple myeloma cell lines removed from patients with multiple myeloma that were both sensitive and resistant to conventional chemotherapy. The drug appeared to induce myeloma cells into apoptosis by blocking the production of a protein that is required for cancer-cell survival. Seliciclib, Cyclacel's leading Cyclin Dependent Kinase inhibitor drug, is in Phase II for multiple myeloma, B-cell chronic lymphocytic leukemia and mantle-cell lymphoma.

Genta Inc., of Berkeley Heights, N.J., said preliminary results of an ongoing trial suggest that stepped dosing of Genasense (oblimersen sodium) might reduce the incidence of a cytokine-release reaction in patients with chronic lymphocytic leukemia. So far, 20 patients have received Genasense at a dose of 1.5 mg/kg/day for seven days during their first cycle with fludarabine and rituximab (Rituxan, Genentech Inc. and Biogen Idec Inc.), and were then escalated to a standard dose of 3 mg/kg/day in subsequent cycles. To date, no episodes of the cytokine-release reaction have been observed.

GlycoGenesys Inc., of Boston, said an vitro study showed for the first time that its lead drug candidate, GCS-100LE, triggered cell death in both B-cell malignant cell lines and primary cancer cells taken from patients with chronic lymphocytic leukemia. Currently in a Phase I trial, the carbohydrate-based compound is being developed for solid tumors and multiple myeloma.

Icagen Inc., of Research Triangle Park, N.C., presented positive results from its Phase II trial of ICA-17043, a small molecule under development in sickle cell anemia and related genetic variants. ICA-17043, which is being developed for once-daily oral administration, has received orphan drug designation and fast-track status. The Phase II trial involved 90 patients and was conducted at 19 academic medical centers across the U.S. The primary efficacy endpoint was the change in hemoglobin level from baseline to the end of the study.

ILEX Oncology Inc., of San Antonio, reported results of 19 additional patients in a pivotal Phase II trial of clofarabine. The company said the additional data support a 30 percent response rate, defined as complete remissions, complete marrow remissions in the absence of platelet recovery and partial remissions, in children with refractory or relapsed acute lymphoblastic leukemia. In children with acute myeloid leukemia, a 26 percent response rate was observed. The findings mark the first update on clofarabine since a new drug application was submitted to the FDA earlier this year. The agency's Oncologic Drugs Advisory Committee last week recommended accelerated approval of clofarabine for acute lymphoblastic leukemia, and the company expects a final decision on or before the Prescription Drug User Fee Act date, which expires on Dec. 30.

Ligand Pharmaceuticals Inc., of San Diego, said interim Phase II data showed a 53 percent response rate in 17 patients with relapsed/refractory T-cell non-Hodgkin's lymphoma treated with Ontak (denileukin diftitox), with an additional 29 percent exhibiting stable disease. Of the nine patients whose tumors positively expressed the p55 (CD25) component of the IL-2 receptor, 67 percent showed a complete or positive response.

Maxim Pharmaceuticals Inc., of San Diego, reported additional data from a Phase III trial of Ceplene plus interleukin-2 for acute myeloid leukemia patients in complete remission. Findings included an updated "p" value (p=0.0096) for the primary endpoint of leukemia-free survival; the previously reported preliminary "p" value (p=0.026) only stratified the patient population by complete remission status and did not additionally stratify by country as set forth in the study protocol. Other data included details of the demographics, risk factors and other baseline characteristics of the patient population, which the company said were all well balanced.

Millennium Pharmaceuticals Inc., of Cambridge, Mass., said overall response rates from ongoing investigator-initiated studies evaluating Velcade (bortezomib) in combination with other commonly used agents in untreated multiple myeloma ranged from 95 percent to 73 percent; complete and near-complete responses were observed. Also presented was the final data analysis of APEX, a randomized Phase III study of patients who had relapsed after one or more lines of prior therapy. Velcade was significantly superior to high-dose dexamethasone based on time to progression, survival, overall response rates and complete response rates. Other results stemmed from several studies evaluating the product's efficacy and safety in patients with aggressive and indolent subtypes of non-Hodgkin's lymphoma. In three ongoing Phase II studies, the overall response rates with single-agent Velcade in follicular lymphoma ranged from 60 percent to 17 percent, and from 54 percent to 39 percent in mantle-cell lymphoma.

Pharmacyclics Inc., of Sunnyvale, Calif., said Phase I results indicate that Xcytrin (motexafin gadolinium) injection has clinical activity when used as a single agent for refractory chronic lymphocytic leukemia. Evidence of antitumor activity, observed in three of 13 patients, was indicated by a decrease in leukemic white blood cell count, decrease in lymph node size and/or a reduction in the size of an enlarged spleen. One responding patient experienced massive necrosis of large cell transformation, the company said, and Xcytrin was found to accumulate in circulating tumor cells in patients after repeated doses and to activate Akt (protein kinase B) within the tumor cells of some patients, providing evidence of its in vivo biologic activity.

Royal London Hospital reported Phase I results showing that a thrombopoietic agent, AMG531, was well tolerated and capable of increasing platelet counts in patients with immune thrombocytopenic purpura, when doses equivalent to more than 1 mcg/kg were given. The product functions by activating the hormone receptor necessary for growth and maturation of megakaryocytes. Separate Phase II results, reported by researchers from Massachusetts General Hospital in Boston, showed that while a platelet response was observed with two dose levels, patients on the lower dose maintained counts within the target range of more than 50,000 platelets per microliter but less than 450,000 platelets per microliter. The response variability suggests that individual dose adjustments might be necessary to achieve the optimal outcome for each patient.

University of Ulm in Germany said subcutaneously administered MabCampath (alemtuzumab, ILEX Oncology Inc.) was an effective therapy for genetic high-risk patients with chronic lymphocytic leukemia. The overall response rate to the drug, called Campath in the U.S., was 36 percent in 44 patients refractory to chemotherapy with fludarabine. The median progression-free survival time was 9.7 months, and median overall survival time was 13.1 months. Responses to MabCampath were observed in seven of 13 patients with a 17p deletion, 14 of 27 patients with unmutated VH and five of 13 with an 11q deletion.

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