The following data were presented at the American Society of Hematology meeting in Orlando, Fla.

Actinium Pharmaceuticals Inc., of New York, presented data from the phase I portion of the firm's phase I/II trial of alpha particle immunotherapy Actimab-A in acute myeloid leukemia patients older than 60 who have not received prior therapy and have declined or are unsuitable for intensive induction chemotherapy. After cycle one, eight of 11 patients (73 percent) evaluated had mean bone marrow blast reduction of 72 percent. Objective responses were seen in four of 14 patients (29 percent) after one cycle of therapy, with one patient achieving complete remission, two patients achieving complete remission with incomplete platelet count recovery and one patient achieving complete remission with incomplete blood count recovery.

Alexion Pharmaceuticals Inc., of Cheshire, Conn., said researchers presented data from the International Paroxysmal Nocturnal Hemoglobinuria (PNH) Registry that advance the understanding of PNH and provide information for the medical community on the long-term management of the disease, including the progression of symptoms in untreated patients with PNH and the continued benefits of ongoing Soliris (eculizumab) treatment regardless of transfusion history. Researchers also presented data from a long-term follow-up study evaluating the effectiveness of Soliris in preventing thrombotic microangiopathy (TMA) in patients with atypical hemolytic uremic syndrome (aHUS). Both PNH and aHUS are severe, ultra-rare diseases caused by chronic uncontrolled complement activation. For the primary endpoint, researchers reported that the TMA event rate was 63 percent lower during periods of Soliris treatment compared to periods of treatment discontinuation. Additionally, the rate of TMA events during periods of on-label dosing of Soliris was 74 percent lower than during periods of treatment discontinuation and was also 57 percent lower compared with periods when patients were on treatment but receiving non-labeled dosing.

Beigene Ltd., of Beijing, presented initial data from an ongoing phase I study of BGB-3111, a small-molecule inhibitor of Bruton's tyrosine kinase, showing the drug is well tolerated and demonstrated single-agent activity in a range of B-cell malignancy subtypes. Data from a total of 39 patients showed no dose-limiting toxicities, and no maximum tolerated dose was reached. The 320-mg once-daily and 160-mg twice-daily doses are being further explored in the ongoing dose-expansion trial.

Bellicum Pharmaceuticals Inc., of Houston, presented preclinical data from studies of its Cidecar CAR T-cell technology, including candidate BPX-401, showing that tumors can be eliminated quickly and safely with the Cidecar co-stimulatory domain MC and safety switch. Data showed the addition of the MC co-stimulatory domain led to a significant increase in in vivo activation and persistence of the Cidecar CAR T cells when compared to CARs constructed with conventional co-stimulatory domains CD28 and 4-1BB. Studies also showed that CAR T cells with the MC co-stimulatory domain eliminated cancer cells faster in animal models than CARs using CD28 or 4-1BB.

Biogen Inc., of Cambridge, Mass., and Swedish Orphan Biovitrum AB, of Stockholm, said new data demonstrate that Eloctate (antihemophilic factor [recombinant], Fc fusion protein, marketed as Elocta in Europe) and Alprolix (coagulation factor IX [recombinant], Fc fusion protein) may effectively manage target joint bleeding and maintain low annualized bleeding rates (ABRs) in people with severe hemophilia A and B. Data from a post-hoc analysis of ASPIRE, an ongoing extension of phase III trials A-LONG and Kids A-LONG, in patients with hemophilia A taking Eloctate prophylactically showed that ABRs overall and in target joints were lower than pre-study bleeding rates. Post-hoc analysis from the B-LONG study in hemophilia B patients taking Alprolix prophylactically showed the therapy was effective in reducing the frequency of bleeding episodes overall and in target joints.

Bio-path Holdings Inc., of Houston, said data from the first seven cohorts in phase I and the safety segment of phase II studies of lead candidate BP-100-1.01 (or BP1001, liposomal Grb2 antisense) in the treatment of blood cancers showed the monotherapy treatment was well tolerated at doses up to 90 mg/m2. Of the evaluable patients, all showed a transient drop in circulating blast percentage.

Celator Pharmaceuticals Inc., of Ewing, N.J., reported phase II data showing that Vyxeos (CPX-351), a liposomal form of cytarabine and daunorubicin, did not prolong the QT/QTc interval. The study enrolled 26 patients with newly diagnosed or relapsed/refractory acute myeloid leukemia (AML) or relapsed/refractory acute lymphoblastic leukemia. Thirteen of the 26 patients responded, including responses in each of the three patient populations. The study also showed that no dose adjustment was required in patients with renal impairment. Adverse events were similar in frequency and severity to those described in earlier studies. Separately, Celator assessed health resource utilization (HRU) using data from a previously published, randomized phase II study comparing first-line treatment with Vyxeos to the current standard of care in newly diagnosed older patients (ages 60 to 75) with AML. Treatment arms were compared for number of hospitalizations, total hospital days, patients responding following a single induction, responding patients receiving consolidation therapy in the outpatient setting, event-free survival (EFS) and the ratio of EFS per inpatient days. The data showed that HRU outcomes were favorable for Vyxeos compared to standard therapy. (See BioWorld Today, June 25, 2015.)

Celgene Corp., of Summit, N.J., and Acceleron Pharma Inc., of Cambridge, Mass., reported preliminary results from two phase II trials of luspatercept in patients with beta-thalassemia, highlighting data showing that luspatercept increased hemoglobin levels, reduced transfusion burden, improved health-related quality of life measures and had beneficial effects on liver iron concentration in patients with beta-thalassemia.

Erytech Pharma SA, of Lyon, France, presented updated data from the pivotal phase II/III trial of Graspa (red blood cell-encapsulated L-asparaginase) vs. native L-asparaginase. The two-year survival data confirm the favorable trend observed after one year of follow-up. Median event-free survival was 11.8 months in the native L-asparaginase group and has not been reached yet in the Graspa arm after two years of follow-up. Median overall survival was not reached in either of the treatment arms.

Galena Biopharma Inc., of San Ramon, Calif., reported final data from its GALE-401(anagrelide controlled release) phase II trial in subjects with thrombocytosis secondary to essential thrombocythemia and other myeloproliferative neoplasms. Data from the 18-patient trial showed that GALE-401 is well tolerated and the efficacy compares favorably to historical anagrelide immediate-release, with reported platelet count best response rates, based on the WHO 2008 criteria, of 11 (61.1 percent) complete responses, four (22.2 percent) partial responses and an overall response rate of 83.3 percent. Fourteen of 18 subjects enrolled experienced a treatment-related adverse event; however, the vast majority were grade I/II, with no patients discontinuing therapy due to progression of disease.

Gilead Sciences Inc., of Foster City, Calif., reported results from a prespecified interim analysis of a phase III study (Study 115) evaluating Zydelig (idelalisib) in combination with bendamustine and Rituxan (rituximab, Biogen Inc. and Roche AG) for patients with previously treated chronic lymphocytic leukemia. The analysis found a 67 percent reduction in the risk of disease progression or death (progression-free survival) in patients receiving Zydelig plus bendamustine/Rituxan (BR) compared to BR alone (p<0.0001). All secondary endpoints, including overall survival, achieved statistical significance.

Immune Design Corp., of Seattle, presented data on G100, its intratumoral TLR4 agonist, demonstrating both direct and abscopal (indirect) tumor regression, as well as tumor-specific, long-term immune protection. In a preclinical model of lymphoma, results showed tumor regression in 60 percent to 100 percent across animal models, and tumor growth inhibition was reported in both injected tumors as well as uninjected tumors. Responders remained tumor-free for at least three months post treatment and were resistant to secondary challenge with the same tumor type.

Johnson & Johnson, of New Brunswick, N.J., said its Janssen Pharmaceuticals Inc. unit and partner Bayer AG, of Leverkusen, Germany, reported results from their real-world XALIA showing that, in people with deep vein thrombosis, the rates of major bleeding and recurrent blood clots for Xarelto (rivaroxaban) in routine clinical practice were generally consistent with those observed in phase III research. Patients taking Xarelto also had shorter length of hospital stays than those given standard anticoagulation.

Juno Therapeutics Inc., of Seattle, reported clinical data from CAR T-cell candidate JCAR015 in adults with relapsed/refractory (r/r) acute lymphoblastic leukemia (ALL), showing an overall complete response (CR) rate of 82 percent (37 of 45 evaluable patients), while minimal residual disease (MRD)-negative CR was reported in 30 of 36 (83 percent) patients who achieved a CR and were evaluable for MRD analysis. Data from a clinical study of JCAR014 showed the addition of fludarabine to cyclophosphamide-based lymphodepletion improved CAR T-cell expansion, persistence and disease-free survival in r/r B-cell adult ALL patients.

Oncolytics Biotech Inc., of Calgary, Alberta, presented data showing that its oncolytic vaccine, Reolysin, in combination with Kyprolis (carfilzomib, Amgen Inc.) in relapsed multiple myeloma showed that all seven patients treated at the full clinical dose had a clinical response. The combination of Kyprolis and Reolysin produced a significant (p=0.005) increase in caspase-3, a marker associated with apoptotic cell death, but to a higher degree in those patients treated at dose level one, and the treatment combination was associated with an increased infiltration of CD8+ T cells and the significant (p=0.005) up-regulation of PD-L1, suggesting that the addition of a PD-1 or PD-L1 inhibitor may further optimize the treatment regimen.

Onconova Therapeutics Inc., of Newtown, Pa., presented data from an ongoing phase I/II study of rigosertib and azacitidine in higher-risk myelodysplastic syndromes (HR-MDS), which identified the recommended dose of oral rigosertib as 560 mg/280 mg twice daily during the phase I portion. Data from 30 evaluable patients in the phase II portion showed that 23 (77 percent) responded per IWG criteria, including six patients who had complete remissions. Hematologic improvement per IWG were noted in 13 patients (50 percent of 26 evaluable patients) and included improvements in erythroid (11 patients), platelet (12 patients) and neutrophil (seven patients) lineages.

Seattle Genetics Inc., of Bothell, Wash., presented data showing that antibody-drug conjugate Adcetris (brentuximab vedotin) in combination with chemotherapy in front-line high-risk diffuse large B-cell lymphoma resulted in an objective response in 21 of 25 evaluable patients (84 percent), including 19 patients (76 percent) with a complete remission and two patients (8 percent) with partial remissions. The estimated progression-free survival rate for CD30-positive patients at both 12 months and 15 months was 83 percent. A separate presentation showed that front-line treatment of mature T-cell lymphoma with Adcetris plus cyclophosphamide, doxorubicin and prednisone resulted in an estimated progression-free survival rate of 52 percent, with no patients receiving a consolidative stem cell transplant in first remission.

Tolero Pharmaceuticals Inc., of Salt Lake City, presented data describing the mechanistic rationale for the FLAM regimen, which combines alvocidib in a time-sequential regimen with cytarabine and mitoxantrone. That regimen has demonstrated consistent activity in front-line and relapsed/refractory acute myeloid leukemia (AML) patients, and results presented demonstrate that alvocidib, a cyclin-dependent kinase-9 inhibitor, blocks super enhancer-regulated transcription of MCL-1 and places AML cells in a heightened state of sensitivity to apoptosis-inducing agents such as cytarabine and mitoxantrone.

Ziopharm Oncology Inc., of Boston, said results from its CD19-specific CAR T-cell therapy programs in which autologous or allogeneic CAR-modified T cells targeting CD19 were administered to recipients with advanced CD19+ malignancies after hematopoietic stem cell transplantation (HSCT). Seven patients with advanced non-Hodgkin lymphoma (NHL) were treated with autologous cells, all of whom remained alive and six of whom remained in complete remission at a median 25.5 months of follow-up, translating to a three-year progression-free survival (PFS) of 83 percent and a three-year overall survival (OS) of 100 percent. Nineteen patients with advanced acute lymphoblastic leukemia and NHL were treated with allogeneic T cells. One-year PFS among those patients was 53 percent and one-year OS was 63 percent. Among eight patients who received donor-derived T cells after haploidentical HSCT, all remained alive and six remained in complete remission after a median of 5.2 months of follow up, translating to a one-year PFS of 75 percent and OS of 100 percent.

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