ATLANTA - At the American Society for Hematology Annual Meeting, the halls were abuzz with multiple biotech stories. As always, cancer got a lot of attention. Among many other studies, both Millennium Pharmaceuticals and Celgene presented data on their multiple myeloma drugs. Both companies showed positive results for patients, though not for stock prices; Millennium finished the day up, while Celgene was down.

But the distinction of having an abstract selected for the scientific plenary session went to Amgen Inc. The company presented the results of two Phase III studies and an extension study on its AMG-531 for the bleeding disorder idiopathic thrombocytopenic purpura on Sunday and Monday, and Phase III data from splenectomized patients were presented in the plenary session.

Data on GlaxoSmithKline plc's eltrombopag, which appeared in the Nov. 28, 2007, issue of the New England Journal of Medicine, also were presented by James Bussel of Weill Cornell Medical College, who presented one of Amgen's studies, as well.

Thrombocytopenia, or low platelet count, can be the consequence of a number of disease states - or their treatments, such as chemotherapy. In the autoimmune condition idiopathic thrombocytopenic purpura, the primary problem is that platelets are coated with autoantibodies and destroyed by the immune system, but there are also fewer platelets than normal being produced in the first place.

AMG-531 works by increasing both the production of platelets and their circulation time in the blood. The drug is a combination of a peptide sequence that stimulates the TPO receptor, leading to increased platelet production, and an antibody that prevents the peptide from being degraded. The peptide sequence of AMG-531 has no homology to endogenous thrombopoietin, making it less likely that patients will develop antibodies to it; indeed, only one patient developed such antibodies, and they disappeared after discontinuing the drug.

At the meeting, Amgen reported results from two separate studies, with patients whose spleens had or had not been removed. In both studies, patients received weekly doses of AMG-531 for 24 weeks. Platelet levels were monitored throughout the study and for 12 weeks afterward.

The overall response rate, which could be a either a transient or a durable increase in platelet count, was nearly 80 percent for splenectomized and nearly 90 percent for non-splenectomized patients. All patients taking AMG-531 were able to either eliminate or reduce concurrent medications. Bleeding occurred at the same rate in treatment and control groups, prompting one speaker to wonder during the question-and-answer session whether the platelets were functional. But presenter James Bussel said that bleeding was euqivalent "because we don't let patients bleed" - instead, patients receive so-called rescue medication when their platelet counts fall to dangerously low levels.

The company also presented interim data from a long-term extension study that has followed some patients for more than two years.

Though a few patients sustained the increase in platelet levels when they were no longer taking the drug, that is not the norm: Presenting data from the splenectomized patients at the Sunday plenary, presenter Terry Gernsheimer, said that platelet counts usually fell within a few weeks after the drug was discontinued.

Amgen has filed a new drug application based on the studies. The company also is testing AMG-531 in myelodysplastic syndrome, and updated results from that study also were presented Monday.

In other ASH news:

• Alexion Pharmaceuticals Inc., of Cheshire, Conn., reported that patients with a rare blood disorder called paroxysmal nocturnal hemoglobinuria (PNH) were found to be six times more likely than the general public to have chronic kidney disease, as shown in an ongoing open-label clinical study. Additionally, results from clinical studies in patients with PNH indicated that long-term treatment with Soliris (eculizumab) was associated with significant improvement and stabilization of kidney function. In a separate presentation of results from the same clinical studies, the long-term reduction in hemolysis with Soliris therapy was associated with sustained reduction in thrombosis and improvements in fatigue, overall quality of life, as well as anemia as measured by reductions in transfusions in a diverse population of patients with PNH. Soliris continued to be safe and well-tolerated throughout the open-label study.

• Antisoma plc, of London, said positive preclinical data supported the ongoing Phase II trial of AS1411 in acute myeloid leukaemia. Researchers from the Medical University of South Carolina showed that AS1411 killed AML cells with high potency and associated that with downregulation of the apoptosis-blocking protein Bcl-2.

• Avalon Pharmaceuticals Inc., of Germantown, Md., said its Beta-catenin pathway inhibitor program showed the small-molecule compound family has potent inhibitory effects on Wnt/Beta-catenin signaling in multiple myeloma cells. The Beta-catenin pathway is activated in the majority of MM cells, and is known to play a critical role in myeloma cell survival. The presentation described inhibition of cell growth, decrease in Beta-catenin protein levels and potent induction of apoptosis in myeloma cells by the Beta-catenin pathway inhibitors.

• ChemGenex Pharmaceuticals Ltd., of Melbourne, Australia, disclosed positive clinical data from the first 21 patients enrolled in its ongoing Phase II/III trial of omacetaxine mepesuccinate (formerly known as Ceflatonin). The poster presentation, authored by a team of leading international hematologists, reported both complete hematologic and cytogenetic responses lasting more than one year in chronic myeloid leukemia patients with the T315I mutation who were resistant to imatinib (Gleevec, Novartis AG).

• Cyclacel Pharmaceuticals Inc., of Berkeley Heights, N.J., reported updated results from a Phase I trial of sapacitabine (CYC682), an oral nucleoside analogue, demonstrating the compound's favorable safety profile and anti-leukemic activity in patients with relapsed and refractory acute myelogenous leukemia and myelodysplastic syndromes, when administered by two different dosing schedules.

• Cytokinetics Inc., of South San Francisco, presented interim data from a Phase I/II clinical trial evaluating SB-743921 in patients with non-Hodgkin's lymphoma (NHL) and Hodgkin's disease. Presenters concluded that SB-743921 is well tolerated without prophylactic granulocyte-colony stimulating factor (GCSF) in doses less than 6 mg/m2 when given on day 1 and day 15 of a 28-day schedule. To date, the best response observed has been a partial response in a patient with Hodgkin's disease out of 23 patients evaluable for efficacy. In that interim analysis, grade 3 or 4 neutropenia was the most common toxicity reported and grade 3 or 4 non-hematological toxicities have been rare. In particular, there has been no evidence of neuropathy. The 6 mg/m2 cohort will be expanded to include up to six additional evaluable patients prior to a final decision on further dose escalation beyond 7 mg/m2 without primary GCSF prophylactic support. Efficacy signals in both NHL and Hodgkin's disease will be explored in Phase II once the MTDs, one with and one without primary GCSF prophylaxis, are determined.

• EntreMed Inc., of Rockville, Md., presented preclinical results in preclinical leukemia models for its antimitotic agent, ENMD-1198, in combination with vincristine. Data presented demonstrated that ENMD-1198, administered as a single agent, is effective in significantly delaying the growth of leukemia xenografts in vivo. Combination studies with ENMD-1198 and another microtubule targeting agent commonly used in the treatment of leukemias, vincristine, demonstrated synergistic effects on leukemia cells in vitro and tolerability of doses that prolonged survival in leukemia xenograft models. Entremed also reported that preclinical study results demonstrated that ENMD-981693, an oral, multitarget kinase inhibitor with a unique kinase selectivity profile and multiple mechanisms of action, inhibits Aurora A, VEGFR2, FGFR1, FGFR3s and Src activation in tumors in vivo. ENMD-981693 demonstrated tumor regression and significant growth inhibition in multiple myeloma xenografts, including tumors that have high levels of constitutively active FGFR3, a mutation found in a subset of multiple myeloma patients that promotes disease progression.

• GlaxoSmithKline, of London, presented data on the long-term safety and efficacy of its investigational drug Promacta (eltrombopag) for the treatment of chronic idiopathic thrombocytopenic purpura (ITP). The preliminary results from the EXTEND (Eltrombopag eXTENded Dosing) study showed that of patients with a baseline platelet count of less than 30,000/microliters, 73 percent achieved a platelet count of greater than or equal to 50,000/microliters. The average treatment period for all patients, from the ongoing treatment study, has lasted almost 22 weeks (five months) so far. Those results suggested that PROMACTA sustains increased platelet counts during long-term treatment.

• Hana Biosciences, of South San Francisco, presented results from both clinical and nonclinical studies of Marqibo (vincristine sulfate injection, Optisome) showing that with or without pulse dexamethasone it appears to have clinically meaningful activity in heavily pre-treated adults with acute lymphoblastic leukemia. Out of the 52 patients in Phase I and Phase II trials, eight complete remissions and three partial remissions were observed for an overall response rate of 21 percent. An additional 12 patients (23 percent) achieved hematological improvements such as clearance of marrow blasts and platelet transfusion independence. Five responders were able to undergo allogeneic stem cell transplantation following therapy with Marqibo. The maximum-tolerated dose was established in the Phase I trial as 2.25 mg/m2 without dose capping.

• ImmunoGen Inc., of Cambridge, Mass., said AVE9633 demonstrated evidence of biological activity in multiple patients with relapsed/refractory acute myeloid leukemia and was found to be generally well tolerated. Highly favorable preclinical findings also were reported for SAR3419, a TAP compound now in clinical testing for the treatment of non-Hodgkin's lymphoma and other B-cell malignancies. AVE9633 is in Phase I development and consists of ImmunoGen's DM4 cell-killing agent and huMy9-6 CD33-binding antibody. ImmunoGen initially developed AVE9633 and licensed the compound to Paris-based Sanofi-Aventis. Evidence of biological activity was noted in seven of the seventeen patients.

• Innovive Pharmaceuticals Inc., of New York, presented results from a pilot study examining INNO-305, a Wilms Tumor Protein (WT1) heteroclitic peptide immunotherapeutic vaccine, in patients with myeloid and thoracic neoplasms. Preliminary data from the pilot study suggested repeat administration with INNO-305 is well tolerated and immune response can be elicited following three vaccinations

• Keryx Biopharmaceuticals Inc., of New York, said that results of Phase I study of Perifosine (KRX-0401) in combination with Velcade (bortezomib) showed clinical activity in patients with relapsed/refractory multiple myeloma. An overall response rate of 56 percent was reported with an additional 31 percent of patients achieving stable disease. In addition, results of a Phase II multicenter study of Perifosine in combination with dexamethasone showed promising activity with manageable toxicity in patients with relapsed/refractory multiple myeloma. Of the 29 patients currently evaluable for response on the combination, an overall response rate of 35 percent was achieved, with an additional 52 percent of patients achieving stable disease. Six patients remain on treatment with duration of response ranging from 15 to 70 weeks, the firm said.

• Kosan Biosciences Inc., of Hayward, Calif., reported that data from a dose-escalating Phase Ib clinical trial of Hsp90 inhibitor tanespimycin (KOS-953) in combination with Velcade (bortezomib) showed durable antitumor activity and tolerability in patients with multiple myeloma who previously had progressed following treatment with multiple conventional therapies. Responses were seen across dose levels in the bortezomib-naive, pretreated and refractory patients. Both formulations demonstrated activity, and the combination was manageable relative to safety, with no grade 3 neurotoxicity to date, the company said, adding that the study's finding supported the potential neuroprotective effect of tanespimycin. The data from the ongoing trial still are being evaluated, and multiple patients remain on study, the firm reported. Because the overall response rate appears to be lower than previously reported, Kosan said it is investigating whether there were patient characteristics that may have contributed to the lower response, including the possibility that patients added to the study since the data were last reported represented a more advanced and heavily pretreated population.

• Osiris Therapeutics Inc., of Columbia, Md., disclosed results from the compassionate use evaluation of Prochymal, an adult stem cell therapy, for the treatment of pediatric patients suffering from end-stage graft-vs.-host disease. Complete disease resolution was achieved in 58 percent of children given Prochymal as rescue agent for severe treatment resistant GvHD, resulting in a fourfold improvement in 100-day survival.

• PDL BioPharma Inc., of Redwood City, Calif., presented clinical and preclinical data on HuLuc63, a humanized monoclonal antibody that binds to human CS1, a cell-surface glycoprotein that is highly expressed on multiple myeloma cells but minimally expressed on normal cells. The antibody currently is being evaluated in a Phase I study as a monotherapy for the treatment of relapsed/refractory MM.

• Pharmacyclics Inc., of Sunnyvale, Calif., said that data from a Phase I/II study demonstrated a 59 percent overall response rate in patients with multiply recurrent non-Hodgkin's lymphoma (NHL) who were treated with Xcytrin injection (motexafin gadolinium) in combination with Zevalin (Yttrium-Ibritumomab Tiuxetan) and 48 percent complete response rate in patients with multiply recurrent NHL. In patients who were Rituxan (rituximab) refractory, the overall response rate was 86 percent, with a 64 percent complete response rate. In patients with aggressive lymphoma, the overall and complete response rate was 22 percent. In addition, the firm said that data from preclinical studies demonstrated antitumor activity in lymphoma with its Bruton's tyrosine kinase (BTK) inhibitor and with its novel histone deacetylase (HDAC) inhibitor in combination with Velcade (bortezomib). Results of that study demonstrated that PCI-32765 inhibits growth of those tumor cells by inhibiting BCR signaling, a critical factor in the survival of NHL cells. In animal studies, a single oral dose of PCI-32765 inhibited BTK activity, required for BCR signaling, for up to 24 hours.

• Sangamo BioSciences Inc., of Richmond, Calif., presented positive data in a mouse tumor model from its program to develop a novel cell therapy using its zinc finger DNA-binding protein nuclease (ZFN) technology for treatment of glioblastoma multiforme (GBM), a progressive and usually fatal brain cancer. Sangamo scientists have engineered ZFNs specifically targeted to the glucocorticoid receptor gene. Data were presented demonstrating the ZFNs cleave their intended target sequences with high specificity and efficiency resulting in the knockout of GR and the creation of glucocorticoid resistant cells. Those zetakine-positive, GR-negative T-cells were demonstrated to kill glioblastoma cells in the presence of dexamethasone in vitro and in vivo in a mouse model of GBM.

• Seattle Genetics Inc., of Seattle, announced positive data from a Phase Ia clinical trial of SGN-33 (lintuzumab) demonstrating multiple complete remissions at well-tolerated doses in patients with acute myeloid leukemia (AML). Preclinical data also were presented indicating the anti-leukemic activity of SGN-33 both as a single agent and when used in combination with lenalidomide (Revlimid(R)) in AML, and the enhanced activity of SGN-40 when used in combination with chemotherapy regimens in non-Hodgkin's lymphoma. SGN-33, or lintuzumab, is a humanized monoclonal antibody that targets the CD33 antigen, which is expressed on a number of hematologic malignancies, including AML, MDS and several myeloproliferative diseases.

• Sunesis Pharmaceuticals Inc., of South San Francisco, presented positive results for SNS-595 in relapsed or refractory acute leukemia patients. In a Phase 1 clinical trial, SNS-595 was generally well tolerated with anti-leukemic clinical activity when administered either once- or twice-weekly at biologically active doses. In addition, nonclinical data showing that SNS-032 induces apoptosis in chronic lymphocytic leukemia (CLL) cells are being presented. SNS-032 is currently in a Phase 1 clinical trial in patients with CLL or multiple myeloma.

• SuperGen Inc., of Dublin, Calif., said data showed that its lead JAK2 kinase inhibitors prevent cancer cell proliferation in nonclinical models. SuperGen said it used its CLIMB technology to build several models that were utilized for screening 2.3 million virtual small-molecule compounds. The process generated a subset of leads that were screened using in silico algorithms to identify druggable candidates to pursue. Testing of the lead candidates in treated leukemia cell cultures indicated that the JAK2 kinase inhibitors were active against both wild-type and mutant JAK2 kinase activity and caused potent inhibition of cancer cell proliferation. In addition, the firm said that its CLIMB technology was used in lead development and design of small-molecule inhibitors of the Pim kinase, which are overexpressed in many cancer types, including acute myelogenous leukemia and acute lymphoblastic leukemia. Leads were screened to identify those with inhibitory activity with low nanomolar IC50 concentrations. Data supported further development of the lead compounds in hematological malignancies, the firm said.

• Tekmira Pharmaceuticals Corp., of Vancouver, British Columbia, and its partner Hana Biosciences Inc., of South San Francisco, said that clinical data showed that Marqibo (vincristine sulfate injection, Optisome) with dexamethasone showed activity in acute lymphoblastic leukemia (ALL) in heavily pretreated adults. The data were from a Phase II trial of single agent Marqibo given at 2 mg/m2 (no dose-capping) every two weeks and a multicenter dose-escalation Phase I trial of Marqibo in combination with pulse dexamethasone administered on a weekly schedule. In total, 52 adult patients with relapsed or refractory ALL were treated in the two studies combined, and all patients previously had received and failed conventional vincristine containing therapy, with no restrictions on the number of prior therapies. Of the 52 patients, eight complete remissions and three partial remissions were observed for an overall response rate of 21 percent. An additional 12 patients achieved hematological improvements, such as clearance of marrow blasts and platelet transfusion independence. Five responders were able to undergo allogeneic stem cell transplantation following therapy with Marqibo, the firm said.

• Telik Inc., of Palo Alto, Calif., presented positive results from the multicenter Phase I dose-escalation study of Telintra (ezatiostat HCl) Tablets in myelodysplastic syndrome (MDS) that it said supported the initiation of Phase II clinical trials. The tablets were well tolerated and no dose-limiting toxicities were observed. The most common non-hematologic toxicities were mild Grade 1 and 2 nausea, diarrhea and vomiting. Blood concentrations of the active metabolite increased with dose levels. Telintra is an investigational small molecule designed to stimulate the production of blood cells in the bone marrow for the potential treatment of cytopenias associated with MDS or chemotherapy.

• Vion Pharmaceuticals Inc., of New Haven, Conn., said preliminary data from its pivotal Phase II trial of its lead anticancer agent Cloretazine (VNP40101M) in elderly patients with de novo poor-risk acute myelogenous leukemia (AML) showed that the product achieved its targeted response rate. The overall complete response rate was 35 percent, 93 percent of which occurred after first induction treatment. The Phase II trial, started in March 2006, was conducted in 17 sites in North America and Europe. Patients received induction therapy of 600 mg/m2 of Cloretazine in a 60-minute infusion. Second induction was permitted between days 35 and 60 in patients with bone marrow improvement but residual disease. Patients who responded could receive consolidation therapy with a continuous infusion of 400 mg/m2 of cytarabine for five days.

• Xanthus Pharmaceuticals Inc., of Cambridge, Mass., announced results from an independent study of Xanafide (amonafide malate) in multidrug-resistant (MDR) leukemia and myeloma cell lines and in pretreatment marrow samples from patients with secondary acute myeloid leukemia (s-AML). The study demonstrated that the uptake, efflux and cytotoxicity of Xanafide were unaffected by MDR proteins expressed in AML cells, and s-AML cells in particular, while other topoisomerase II inhibitors evaluated in the study were affected by the expression of those proteins. Increased levels of the proteins are a common cause of multidrug-resistance of AML cells to currently used treatments, so the study indicated that Xanafide may not be subject to that mode of drug resistance. Xanafide's ability to overcome resistance in s-AML cells may explain the encouraging complete remission rates previously observed in Phase I and Phase II trials of Xanafide in AML

• ZymoGenetics Inc., of Seattle, presented interim results from a Phase I trial with interleukin 21 (IL-21) in combination with rituximab (Rituxan, Genentech Inc. and Biogen Idec Inc.) in patients with relapsed low-grade B cell lymphoma. IL-21 with rituximab was well tolerated and resulted in anti-lymphoma activity, the company said. Evaluated were three dose levels of IL-21 (30, 100 and 150 mcg/kg), given intravenously once per week in combination with a standard dose of rituximab (375 mg/m2) for four weeks.