Celator Pharmaceuticals Announces VYXEOS Shows No QT/QTc Interval Prolongation
Celator Pharmaceuticals, Inc. recently announced that a Phase II pharmacokinetic and pharmacodynamics (PK/PD) study evaluating the effects of VYXEOS (CPX-351) on cardiac depolarization/repolarization has concluded and VYXEOS did not prolong the QT/QTc interval.
This study, in adult patients with acute hematologic malignancies, was conducted to support the US FDA requirements of a New Drug Application (NDA), which Celator hopes to file for VYXEOS after completing the ongoing Phase III clinical study in patients with high-risk (secondary) acute myeloid leukemia (AML).
The QT interval represents the amount of time the heart’s electrical system takes to depolarize and repolarize during each heartbeat. Prolongation of the QT interval may increase the risk of cardiac arrhythmias and is a biomarker for Torsade de Pointes, a sometimes fatal form of ventricular tachycardia. An intensive QT study is a specialized clinical trial conducted in a relevant patient population designed to assess whether an investigational medication has the potential to prolong the QT interval.
This open-label, single arm, Phase II study measured the effects of VYXEOS on cardiac repolarization during the first induction cycle and correlated electrophysiologic changes, as measured by the QT/QTc interval, with a detailed pharmacokinetic assessment of cytarabine and daunorubicin and their metabolites using exposure response modeling methodology. The study completed enrollment in June 2015. Each patient received a first induction of VYXEOS on days 1, 3, and 5 and, if necessary, a second induction for patients with reduced leukemia burden not yet achieving a disease-free state.
Responding patients were eligible for up to four consolidation courses. Patients with newly diagnosed de novo and newly diagnosed secondary AML, relapsed/refractory AML, and relapsed/refractory acute lymphoblastic leukemia (ALL) were enrolled. Responses were seen in patients with de novo AML, newly diagnosed secondary AML, relapsed AML, and refractory ALL. Adverse events were consistent with those previously reported.
Data from this study has been accepted for poster presentation at the 57th American Society of Hematology (ASH) Annual Meeting. The abstract, titled CPX-351 ((Cytarabine:Daunorubicin) Liposome Injection, (VYXEOS)) Does Not Prolong QTcF Intervals, Requires No Dose Adjustment for Impaired Renal Function and Induces High Rates of Complete Remission in Acute Myeloid Leukemia, will be presented on Sunday, December 6, 2015.
“We continue to work expeditiously to bring VYXEOS before the FDA as a potential new treatment option for patients with acute hematologic malignancies,” said Scott Jackson, Chief Executive Officer of Celator. “Clinical pharmacology studies are required by the FDA for new drugs in development, so we are pleased to announce this top-line result and expect to report additional information from this study at the ASH Annual Meeting.”
Celator’s Phase III study comparing VYXEOS to the current standard of care, known as 7+3, is being conducted in patients with high-risk (secondary) AML. The Phase III study completed enrollment in November 2014. Initial data, from a secondary endpoint, showed an improvement in induction response rate in favor of VYXEOS over the 7+3 control arm: 47.7% versus 33.3% respectively, for a 43.2% relative improvement. The study’s primary endpoint, overall survival, is expected in the first quarter of 2016 along with important safety information.
Celator Pharmaceuticals, Inc., with locations in Ewing, NJ, and Vancouver, BC, is a clinical-stage biopharmaceutical company that is transforming the science of combination therapy, and developing products to improve patient outcomes in cancer. Celator’s proprietary technology platform, CombiPlex, enables the rational design and rapid evaluation of optimized combinations incorporating traditional chemotherapies as well as molecularly targeted agents to deliver enhanced anti-cancer activity. CombiPlex addresses several fundamental shortcomings of conventional combination regimens, as well as the challenges inherent in combination drug development, by identifying the most effective synergistic molar ratio of the drugs being combined in vitro, and fixing this ratio in a nano-scale drug delivery complex to maintain the optimized combination after administration and ensure its exposure to the tumor. Celator’s pipeline includes lead product, VYXEOS (CPX-351), a liposomal formulation of cytarabine:daunorubicin being studied for the treatment of acute myeloid leukemia; CPX-1, a liposomal formulation of irinotecan:floxuridine being studied for the treatment of colorectal cancer; and a preclinical stage product candidate, CPX-8, a hydrophobic docetaxel prodrug nanoparticle formulation, being studied by the National Cancer Institute’s Nanotechnology Characterization Laboratory. The company is advancing the CombiPlex platform and broadening its application to include molecularly targeted therapies. For more information, visit Celator’s website at www.celatorpharma.com. Information on ongoing trials is available at www.clinicaltrials.gov.
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