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Vepoloxamer Does Not Meet Primary Endpoint in Phase III Study in Patients With Sickle Cell Disease
In the phase III EPIC ( Evaluation of Purified Poloxamer 188 [ MST-188 ] In Crisis ) study , vepoloxamer , an investigational therapy for sickle cell disease ( SCD ), did not reduce the mean duration of vaso-occlusive crisis ( VOC ; the study ’ s primary endpoint ) compared with placebo ( 82 hours vs . 78 hours , respectively ; p = 0.09 ).
There also were no statistically significant differences in secondary endpoints , including the rate of re-hospitalization for VOC and occurrence of acute chest syndrome , according to a press release from Mast Therapeutics , Inc ., the drug ’ s manufacturer . Vepoloxamer appeared to be well tolerated in this patient population , with no statistically significant differences in treatment-related adverse events between vepoloxamer and placebo . No deaths occurred during the study .
EPIC was a randomized , double-blind , two-arm , placebo-controlled trial that assessed outcomes in 388 patients with SCD ( 4-46 years of age ) who were hospitalized for acute pain and required treatment with parenteral opioid analgesia . The mean patient age was 15 years , and most patients ( 71 %) were < 18 years old . Many patients ( 61 %) were concurrently receiving hydroxyurea .
Patients were randomized to receive placebo or vepoloxamer 100 mg / kg administered intravenously as a one-hour infusion , followed by continuous maintenance infusion ( 30 mg / kg / hour ) for at least 12 hours ( up to 48 hours ) or placebo .
In a statement to ASH Clinical News , a representative from Mast Therapeutics , Inc ., said , “ While it is disappointing that vepoloxamer was not shown to be effective in this study , we have confidence that the study was well performed and represents the best contemporaneous dataset documenting VOC in SCD . We are confident the data will provide important insights into mechanisms of injury and more complete information on a well characterized , international cohort of patients on the natural history of disease and course of VOC . We firmly believe the dataset would be useful in future interventional trial design .”
Source : Mast Therapeutics press release , September 20 , 2016 .
CAR T-Cell Therapy Induces Complete Remissions in Aggressive Non- Hodgkin Lymphoma , Now Being Assessed in Combination Regimen
In the phase II ZUMA-1 ( A Phase 1-2 Multi-Center Study Evaluating KTE-C19 in Subjects With Refractory Aggressive Non-Hodgkin Lymphoma ) trial of patients with aggressive non-Hodgkin lymphoma , treatment with the experimental chimeric antigen receptor T-cell ( CAR T-cell ) therapy , KTE-C19 , induced complete remissions ( CR ) in 47 percent of patients and led to an objective response rate ( ORR ) of 76 percent ( p < 0.0001 ).
The study included 62 patients : 51 with diffuse large B-cell lymphoma ( DLBCL ) and 11 with either transformed follicular lymphoma ( TFL ) or primary mediastinal B-cell lymphoma ( PMBCL ). For those with DLBCL , the ORR with KTE-C19 was 76 percent , with a CR rate of 47 percent . In those with TFL / PMBCL , the ORR was 91 percent , with a CR rate of 73 percent .
The most common grade ≥3 adverse events included neutropenia ( 66 %), anemia ( 40 %), febrile neutropenia ( 29 %), thrombocytopenia ( 29 %), and encephalopathy ( 26 %). Serious neurologic toxicity was reported in 34 percent of patients , and serious cytokine release syndrome ( CRS ) was reported in 18 percent of patients . Two treatment-related deaths occurred , including hemophagocytic lymphohistiocytosis and cardiac arrest related to CRS .
Kite Pharma Inc ., the drug ’ s manufacturer , said it will present six-month followup data from 101 patients in early 2017 with outcomes on complete response rates .
KTE-C19 is also being assessed in combination with atezolizumab in a single-arm , open-label , multicenter , phase Ib / II study in patients with refractory DLBCL to examine the safety and efficacy of the combination . The first patient was enrolled in October .
Sources : Kite Pharma press release , September 26 , 2016 ; Reuters , September 26 , 2016 ; Kite Pharma press release , October 6 , 2016 .
FDA Grants Orphan Drug Designation for SB-FIX for Hemophilia B
The FDA granted orphan drug designation to SB-FIX – a zinc finger nuclease – mediated in vivo genome-editing product – for patients with hemophilia B . SB-FIX is designed to be a one-time intravenous treatment that provides stable , continuous production of factor IX proteins throughout a patient ’ s life . A phase I / II , non-randomized , open-label clinical trial to assess the safety , tolerability , and efficacy of SB-FIX in adult patients with hemophilia B is scheduled to take place later this year at five sites in the United States .
Source : Sangamo BioSciences press release , September 6 , 2016 .
Head-to-Head Trial Finds Carfilzomib Not Superior to Bortezomib in Newly Diagnosed Patients With Myeloma
In the head-to-head , phase III CLARION ( Phase 3 Study of Carfilzomib , Melphalan , Prednisone vs Bortezomib , Melphalan , Prednisone in Newly Diagnosed Multiple Myeloma ) study of patients with newly diagnosed MM , carfilzomib did not improve progression-free survival ( PFS ) compared with bortezomib ( median PFS = 22.3 months vs . 22.1 months ; hazard ratio = 0.91 ; 95 % CI 0.75-1.1 ).
The CLARION trial included 955 patients from 213 locations in the United States , South Korea , Spain , and France who were randomized to receive melphalan and prednisone plus bortezomib or carfilzomib . No overall survival difference was seen between the two treatment arms , either .
Fatal treatment-related adverse events were also higher with carfilzomib ( 6.5 %) compared with bortezomib ( 4.3 %; p value not provided ).
Sources : Reuters , September 27 , 2016 ; Amgen news release , September 27 , 2016 .
24 ASH Clinical News November 2016