Assistant Managing Editor

Promising Phase II data of Sunesis Pharmaceuticals Inc.'s quinolone derivative voreloxin in acute myeloid leukemia (AML) sent shares climbing 20.5 percent, positioning the firm for a pivotal program next year and potential partnering discussions.

Sunesis execs steered away from business development discussions during their conference call from the American Society of Hematology meeting in New Orleans, preferring to focus on the clinical data, but Daniel Swisher, president and CEO, said the firm is "carefully evaluating our options for moving the drug forward."

The company has said it plans to sign a partner ahead of beginning Phase III, and Cowen and Co. analyst Eric Schmidt said a deal is "likely" in the first half of 2010.

Shares of the South San Francisco-based firm (NASDAQ:SNSS) closed Tuesday at 53 cents, up 9 cents.

Data presented at ASH, including results from the Phase II REVEAL-1 (Response Evaluation of VorEloxin in AmL) trial, could give voreloxin a bit more visibility in AML, a space for which there are few treatment options but a number of drugs in development. Among products coming down the pipeline include Vion Pharmaceuticals Inc.'s Onrigin (laromustine), though an advisory panel recently recommended against approval based on a single, open-label trial.

Cyclacel Pharmaceuticals Inc., Antisoma plc and Ambit Biosciences Inc. also are pushing AML drugs through the clinic.

Sunesis execs and trial investigators highlighted voreloxin's safety, which could help set it apart from competitors, particularly since elderly AML patients often suffer from co-morbidities that can hinder treatment.

"What we're looking for is something that can be tolerated by most patients," said investigator Robert K. Stuart, professor of medicine in the University of South Carolina's hematology/oncology division. "Once a patient has relapsed, there's nothing short of a stem cell transplant." He added, "I see [voreloxin] as a treatment that can serve as a bridge" between first relapse and transplant.

All 113 elderly patients in the REVEAL-1 study, which tested voreloxin as a single agent in previously untreated AML, had at least one additional adverse risk factor. The trial tested three dosing schedules, and investigators determined that greatest efficacy with best tolerability occurred when patients received 72 mg/m2 of drug at days one and four.

Results from that dosing schedule showed an overall response rate of 38 percent, with a 30-day and 60-day all-cause mortality rate of 7 percent and 17 percent, respectively. Median duration of remission has not yet been reached, and the company said it was too early to evaluate one-year survival.

For the pivotal trial, Cowen's Schmidt is anticipating a trial combining voreloxin and cytarabine, the standard of care for AML.

Data from an ongoing Phase Ib/II trial testing of that combination have shown a remission rate of 31 percent. And the two drugs can be combined without seeing the side effects "beyond what you get with cytarabine alone," Stuart said.

Sunesis' sights are set on an end-of-Phase-II meeting with the FDA, scheduled in the first quarter of next year, with a pivotal program to launch soon after.

Specific Phase III details will have to wait until after that meeting. But, given the Oncology Drugs Advisory Panel negative vote on both Vion's and Genzyme Corp.'s single-arm studies earlier this year, "we can say that it will be a randomized trial," Swisher said, with a survival endpoint. (See BioWorld Today, Sept. 2, 2009.)

As of Sept. 30, Sunesis had a cash position of $3.9 million, though the firm added another $5 million in October through the second tranche of an April private placement.

In other ASH news:

• Acceleron Pharma Inc., of Cambridge, Mass., presented data demonstrating that ACE-536 promotes formation of red blood cells through inhibition of members of the TGF-beta superfamily. Study findings showed that administration of the drug promoted rapid, dose-dependent increases of hemoglobin, hematocrit and red blood cells in several animal species. ACE-536 is in development for anemia and is set to enter the clinic in the first half of 2010.

• Aldagen Inc., of Durham, N.C., presented 14 abstracts including several supporting the clinical importance of adult stem cells expressing high levels of an enzyme known as aldehyde dehydrogenase (ALDH). Duke University and Aldagen presented results of animal experiments modeling the clinical effects of ALD-101 in reducing the time to engraftment following a cord blood transplant. The study was designed to evaluate neutrophil and platelet engraftment of sorted ALDH(br) cell populations in mice, as compared to unsorted cord blood containing the same number of ALDH(br) cells.

• Ambit Biosciences Corp., of San Diego, presented preliminary results from a Phase I trial of AC220, a small molecule optimized as a FMS-like tyrosine kinase inhibitor, in acute myeloid leukemia, showing that the drug was generally well tolerated, with no treatment-related mortality observed. Twenty-three (30 percent) of the 76 total patients responded, including 10 (56 percent) of the 18 FLT3 IDT-positive patients, nine (20 percent) of the 45 FLT ITD-patients and four (31 percent) of the 13 patients whose FLT3 genotype was undetermined. The overall study population had a median survival time of 14 weeks.

• Amgen Inc., of Thousand Oaks, Calif., reported Phase I/II results showing that Nplate (romiplostim) was generally well tolerated compared to placebo in children (ages 12 months to younger than 18 years) with chronic immune thrombocytopenic purpura. Efficacy results showed that Nplate was effective in treating thrombocytopenia compared to placebo, with 88 percent of the 17 Nplate patients achieving both efficacy endpoints during treatment compared to none of the five placebo patients achieving either endpoint.

• Ariad Pharmaceuticals Inc., of Cambridge, Mass., presented data from an ongoing Phase I study of pan-Bcr-Abl inhibitor AP24534 in patients with advanced hematological cancers, including results showing evidence of hematologic, cytogenetic and molecular anticancer activity in heavily pretreated patients with resistant and refractory chronic myeloid leukemia. Of the 20 chronic phase CML patients evaluable for cytogenetic response across all dose levels, 25 percent demonstrated a complete cytogenetic response, 45 percent showed a major cytogenetic response and 60 percent demonstrated any cytogenetic response. A complete hematologic response was observed in 83 percent (10 of 12) of evaluable chronic phase CML patients. No dose-limiting toxicities were observed at dose levels lower than 60 mg.

• Celgene International Sarl, of Boudry, Switzerland, reported data showing that the combination of Revlimid (lenalidomide) and dexamethasone in patients with high-risk smoldering multiple myeloma prolonged time to progression, including complete responses, with manageable toxicity. Results showed an overall response rate of 81 percent, including 30 percent with a very good partial response or better. For patients who completed the initial nine treatment cycles, the overall response rate was 91 percent. After a median follow-up of 14 months, disease progression was observed in two patients (4 percent) in the Revlimid/dexamethasone arm, while 16 (34 percent) progressed to active myeloma in the arm with no treatment. In a separate presentation, Celgene reported Phase II data showing that the combination of Revlimid and Rituxan (rituximab, Genentech Inc. and Biogen Idec Inc.) in indolent non-Hodgkin's lymphoma produced a preliminary overall response rate of 75 percent (12 of 16 patients), including 31 percent who achieved a complete response. In 13 patients with relapsed for refractory follicular NHL, there were 11 responders (85 percent), with five of those (38 percent) achieving complete response.

• CombinatoRx Inc., of Cambridge, Mass., presented preclinical data showing that its adenosine A2A receptor and beta-2 adrenergic receptor agonist oncology programs demonstrated synergistic anticancer activity when combined with standard-of-care therapies in multiple myeloma and other B-cell malignancies.

• Genentech Inc., of South San Francisco, a subsidiary of the Roche Group, and Biogen Idec Inc., of Cambridge, Mass., presented three-year, follow-up data from their Phase III CLL8 trial showing that Rituxan (rituximab) plus fludarabine and cyclophosphamide (FC) chemotherapy helped patients with previously untreated chronic lymphocytic leukemia live longer than with FC alone. Results showed that 87.2 percent of patients in the Rituxan/FC arm were alive at 37.7 months compared to 82.5 percent in the FC-only group. At that time, patients in the Rituxan/FC group had a median progression-free survival of 51.8 months vs. 32.8 months in the FC-only group.

• Gentium SpA, of Villa Guardia, Italy, reported results from its Phase II/III pediatric prevention trial, showing the Defibrotide demonstrated a 40 percent reduction in the incidence of veno-occlusive disease at day 30. Results from a separate Phase III treatment trial showed an improvement in complete response from 9 percent in the historical control arm to 24 percent in the Defibrotide arm. The drug was well tolerated in both studies.

• Genzyme Corp., of Cambridge, Mass., presented early data from a Phase I/II trial suggesting that Mozobil (plerixafor injection) in combination with chemotherapy could offer a therapeutic impact on leukemic cells protected in bone marrow. The trial enrolled 40 patients with relapsed or refractory acute myeloid leukemia who were given Mozobil followed four hours later by AML combination chemotherapy with mitoxantrone, etoposide and cytarabine. Of the 32 patients evaluable for the first follow-up, researchers observed a complete remission in 50 percent, with 13 patients showing a complete remission with normal platelet recovery and three showing complete remission with incomplete platelet recovery.

• Geron Corp., of Menlo Park, Calif., presented interim data from its Phase II data of GRNVAC1, an autologous dendritic cell vaccine targeting telomerase, in acute myelogenous leukemia, which showed that 14 of 20 patients in the study remain in complete clinical remission. Median duration of complete response, including the patients who have relapsed, is 12 months. Geron said follow-up of the patients for about one additional year is required to estimate the impact of vaccination on disease-free survival.

• GlaxoSmithKline plc, of Philadelphia, presented updated long-term survival data from two Phase II studies of Bexxar (tositumomab and iodine I-131 tositumomab). The first study demonstrated that, among 76 patients with previously untreated follicular lymphoma, the 10-year overall survival rate was 83 percent and the 10-year progression-free survival rate was 38 percent. The second study demonstrated that after long-term follow-up, heavily pretreated non-Hodgkin's lymphoma patients refractory to Rituxan (rituximab, Genentech Inc. and Biogen Idec Inc.), experienced a median overall survival of 6.7 years.

• HemaQuest Pharmaceuticals Inc., of Seattle, reported preclinical data showing that HQK-1001 could augment the activity of a range of therapeutic agents that have been used to treat hemoglobin disorders. Early data from the first clinical trials in sickle cell disease and beta thalassemia so far have demonstrated that the drug has a strong safety profile, with early evidence of fetal globin induction, the key pharmacodynamic marker of the agent's therapeutic activity.

• Immunomedics Inc., of Morris Plains, N.J., reported data from three preclinical studies aimed at understanding the mechanism of action of milatuzumab, its anti-CD74 antibody in development for multiple myeloma, non-Hodgkin's lymphoma and chronic lymphocytic leukemia. Among the data presented included results from a study in CLL that indicated the mode of cell death induced by milatuzumab was found to be mediated directly through interaction with CD74 and its ensuing effects on signal transduction. Milatuzumab-induced cell death occurred rapidly, with 57 percent cell survival at four hours and 30 percent at 24 hours, which was superior to that observed with Rituxan (rituximab, Genentech Inc. and Biogen Idec Inc.).

• Incyte Corp., of Wilmington, Del., highlighted its JAK1/JAK2 inhibitor INCB18424 in three presentations, including data demonstrating that the drug continues to provide durable clinical benefits in patients with myelofibrosis, with or without JAK2 activating mutations. In an exploratory study in highly refractory patients with secondary acute myeloid leukemia and other leukemias, INCB18424 was able to induce stable disease, as well as complete and partial responses.

• Memgen, of Dallas, presented positive data evaluating its active cellular immunotherapy product, ISF35, in combination with chemotherapy in resistant chronic lymphocytic leukemia. The ongoing Phase Ib trial's first two patients have both achieved minimal residual disease-negative complete responses. Both patients had high-risk CLL with 17p deletion, which is associated with short survival and resistance to treatment. By comparison, less than 11 percent of patients with that condition achieve a complete response to FCR chemotherapy without ISF35, according to the company.

• Micromet Inc., of Bethesda, Md., reported data from its completed Phase II trial with blinatumomab in patients with B-precursor acute lymphoblastic leukemia (ALL). A total of 21 patients were treated and after having received extensive chemotherapy, all patients had ALL malignant cells persisting in their bone marrow, a disease state referred to as minimal residual disease. The primary endpoint was the elimination of those cancer cells to an undetectable level in at least 22 percent of patients. Data showed 80 percent of the evaluable patients (16 of 20 patients) achieved the primary endpoint, all of them during the first treatment cycle. The responses appear to be durable, with patients free of relapse for currently up to 15 months, the company said. Micromet said the data are expected to lead to a pivotal trial.

• Millennium, of Cambridge, Mass., a subsidiary of Takeda Pharmaceutical Co. Ltd., reported updated results based on a planned median three-year follow-up of patients from its Phase III VISTA trial, showing that patients treated with Velcade (bortezomib), melphalan and prednisone had significantly longer overall survival compared to those receiving melphalan and prednisone alone, translating into a 35 percent reduction in risk of death. Those data formed the basis of a supplemental new drug application, currently under review.

• Novartis Pharmaceuticals Corp., of East Hanover, N.J., reported Phase III data showing that Tasigna (nilotinib) demonstrated statistically significant improvement over Gleevec (imatinib) in treating adult patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase. At 12 months, significantly fewer patients progressed to accelerated or blastic phase on Tasigna 300 mg twice daily than on Gleevec 400 mg once daily (two patients vs. 11 patients). Fewer patients also discontinued due to adverse events in the Tasigna arm vs. the Gleevec arm.

• Pharmacyclics Inc., of Sunnyvale, Calif., reported interim Phase I data showing that its oral Bruton's tyrosine kinase inhibitor PCI-32765 was well tolerated by relapsed or refractory B-cell non-Hodgkin's lymphoma patients and demonstrated an overall response rate of 31 percent in the first two cohorts. In the first cohort, two of seven patients had partial responses, one in mantle-cell lymphoma and one in follicular lymphoma, and one patient had stable disease for about five cycles. In the second cohort, three of nine patients had partial responses, one with mantle-cell lymphoma and two with chronic lymphocytic leukemia, and two patients had stable disease for about two cycles.

• Seattle Genetics Inc., of Seattle, reported data from two Phase Ib trials of dacetuzumab. Data from the first study, which tested the drug in combination with Rituxan (rituximab, Genentech Inc. and Biogen Idec Inc.) and Gemzar (gemcitabine, Eli Lilly and Co.) in multiple myeloma, showed that the combination was generally well tolerated and no maximum tolerated dose was determined. Objective responses were achieved in 50 percent of patients (15 of 30), including eight with complete responses and seven with partial responses, and the median duration of response was 5.1 months. Results from the second study, which tested dacetuzumab with Revlimid (lenalidomide, Celgene Corp.) and dexamethasone in multiple myeloma, showed objective responses in 44 percent of patients (16 of 36), including two complete response and 14 partial responses.

• Semafore Pharmaceuticals Inc., of Indianapolis, presented data from a Phase I trial of SF1126, a small-molecule inhibitor of PI3K and mTOR, in relapsed and refractory myeloma, which showed that the drug suppressed the pathway in tumor cells at well-tolerated doses. Of the eight patients treated to date, one achieved stable disease, as evidenced by urinary protein stabilization following a rapid rise prior to study initiation. The maximum-tolerated dose had not yet been determined.

• Trubion Pharmaceuticals Inc., of Seattle, and Facet Biotech Corp., of Redwood City, Calif., presented data from a Phase I study of TRU-016 in relapsed and refractory chronic lymphocytic leukemia, which showed that, of 33 patients, five were observed with partial responses, including one patient with the 17p deletion cytogenetic abnormality. Two patients with leukemia cutis experienced clearing, one complete and one partial. At the 10 mg/kg dose, four of five patients with elevated peripheral lymphocyte counts were reduced to normal levels. The maximum-tolerated dose has not yet been reached. TRU-016 is a CD37-directed small-modular immunopharmaceutical protein therapeutic.