Acute Myeloid Leukemia

July 4, 2016

Celator Pharmaceuticals issued results of a phase III trial of VYXEOS (cytarabine: daunorubicin) Liposome for Injection (CPX-351) in patients with high-risk acute myeloid leukemia (AML). The randomized, controlled trial enrolled 309 patients, and compared VYXEOS to the conventional cytarabine and daunorubicin treatment regimen (commonly referred to as 7+3) as first-line therapy in older (60-75 years of age) patients. Patients were randomized 1:1 to receive either VYXEOS or 7+3. First induction for VYXEOS was 100u/m2; days one, three and five by 90-minute infusion, and for the control arm was cytarabine 100mg/m2/day by continuous infusion for seven days and daunorubicin 60mg/m2 on days one, two and three (7+3). Second induction for VYXEOS-treated patients was 100u/m2 on days one and three, and the control arm was cytarabine 100mg/ m2/day by continuous infusion for five days and daunorubicin 60mg/m2 on days one and two (5+2). An improvement in overall survival was also observed in FLT3 mutated patients with median overall survival of 10.25 months in the VYXEOS arm compared to 4.55 months in the 7+3 arm. The Hazard Ratio (HR) was 0.57 (p=0.093). In addition, preliminary data on NPM1 and CEBP mutations were presented showing an improvement in response rate and overall survival in patients with these mutations. The company expects to submit a NDA for VYXEOS with the FDA by the end of the third quarter of 2016.

April 11, 2016

BioLineRx issued results from BL-8040’s phase II trial in relapsed or refractory acute myeloid leukemia (r/r AML). The trial was a multicenter, open-label study assessing pharmacodynamics and pharmacokinetic parameters of BL-8040 in combination with Cytarabine (Ara-C). Forty-two patients with r/r AML were enrolled in the study (36 of which received a dose of 1mg/kg and higher). The study included a dose escalation stage followed by an expansion stage. Each patient received a once daily dose of BL-8040 monotherapy (from 0.5 to 2mg/kg) on days one to two, followed by the same dose of BL-8040 plus Ara-C on days three to seven. Extensive pharmacodynamic parameters, such as mobilization of leukemic cells and induction of apoptosis, were assessed after monotherapy with BL-8040 using peripheral blood sampling and bone marrow aspirates at baseline and on day three prior to Ara-C administration. Clinical response to treatment was evaluated by bone marrow biopsy on day 30. Results showed BL-8040, as a single agent and in combination with Cytarabine (Ara-C), was safe and well-tolerated at all doses tested up to and including the highest dose level of 2mg/kg, with no major adverse events (n=45). The composite complete remission rate, including both complete remission (CR) and complete remission with incomplete blood count recovery (CRi), was 38% in subjects receiving up to two cycles of BL-8040 treatment at doses of 1mg/kg and higher (n=39). The company plans multiple additional clinical studies for BL-8040. An AML consolidation treatment is currently being investigated in a large phase IIb study at in Germany.  

April 4, 2016

Celator Pharmaceuticals reported results of a phase III trial of VYXEOS (cytarabine: daunorubicin) Liposome Injection (also known as CPX-351) in patients with high-risk (secondary) acute myeloid leukemia (AML) compared to the standard of care regimen of cytarabine and daunorubicin known as 7+3. The median overall survival for patients treated with VYXEOS in the study was 9.56 months compared to 5.95 months for patients receiving 7+3, representing a 3.61 month improvement in favor of VYXEOS. The hazard ratio (HR) was 0.69 (p=0.005) which represents a 31% reduction in the risk of death versus 7+3. The percentage of patients alive 12 months after randomization was 41.5% on the VYXEOS arm compared to 27.6% on the 7+3 arm. The percentage of patients alive 24 months after randomization was 31.1% on the VYXEOS arm compared to 12.3% on the 7+3 arm. VYXEOS also demonstrated a statistically significant improvement in induction response rate (CR+CRi of 47.7% v. 33.3%; p=0.016) and this significance was maintained for the analysis of CR alone (CR of 37.3% v. 25.6%, p=0.040). Sixty-day all-cause mortality was 13.7% v. 21.2%, in favor of patients treated with VYXEOS. Based on these results the company expects to submit an NDA for VYXEOS with the FDA later this year and submit an MAA with the EMA in the first quarter of 2017. No substantial difference in Grade 3 or higher adverse events was observed between VYXEOS and 7+3. In the intent-to-treat population, Grade 3 or higher, hematologic adverse events were similar for overall infections, febrile neutropenia, and bleeding events. In the intent-to-treat population, Grade 3 or higher, non-hematologic adverse events were similar across all organ systems, including cardiac, gastrointestinal, general systems, metabolic disorders, musculoskeletal, nervous system, respiratory, skin and renal.

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