FDA Grants Accelerated Approval for Vincristine Sulfate Liposome Injection
Thursday, August 09, 2012
The U.S. Food and Drug Administration (FDA) granted accelerated approval for vinCRIStine sulfate LIPOSOME injection (Marqibo®, Talon Therapeutics, Inc.) for the treatment of adult patients with Philadelphia chromosome-negative (Ph-) acute lymphoblastic leukemia (ALL) in second or greater relapse or whose disease has progressed following two or more anti-leukemia therapies.
The approval is based on the rate of complete remission (CR) plus the rate of complete remission with incomplete blood count recovery (CRi) in a single arm, single agent trial of 65 adults in second or greater relapse.
The efficacy of Marqibo® was studied in a single trial, HBS407, which enrolled patients age 18 years or older with Philadelphia chromosome negative ALL in second or greater relapse or whose disease progressed after two or more anti-leukemia treatment regimens. Patients had to have achieved a complete remission (CR) from one of the prior anti-leukemia chemotherapies, defined by a leukemia-free interval of at least 90 days. At the time of screening and enrollment, patients were not eligible for immediate hematopoietic stem cell transplantation. All patients had received prior vincristine sulfate; 22 (34%) had not received asparaginase products.
Fifty-one percent (51%) of patients were male, 45% were under 30 years of age and 11% were age 65 or older. Eighty-five percent had precursor B cell ALL and 15% had precursor T cell ALL. Marqibo® was infused intravenously at 2.25 mg/m2 over 60 minutes every 7 days. Concomitant corticosteroids were not permitted beyond Day 5.
The CR rate was 4.6% (3/65) and the CRi rate was 10.8% (7/65). Among the 10 patients achieving CR or CRi, the median documented remission duration was 28 days (95% CI: 7, 36), and the median duration of time to the first event (relapse, death, or subsequent chemotherapies) was 56 days (95% CI: 9, 65).
The safety of Marqibo® at the dose of 2.25 mg/m2 weekly was evaluated in two single arm trials (HBS407 and VSLI-06) consisting of a total of 83 patients with ALL in second or greater relapse. Adverse reactions were observed in 100% of patients. The most common adverse reactions (>30%) were constipation, nausea, pyrexia, fatigue, peripheral neuropathy, febrile neutropenia, diarrhea, anemia, decreased appetite, and insomnia.
Severe adverse reactions (Grade 3 or greater) occurred in 96% of patients. The most common were infections, neuropathy, febrile neutropenia, neutropenia, anemia, and thrombocytopenia.
Dose reduction, delay or omission occurred in 53% of patients during the treatment.
Adverse reactions leading to treatment discontinuation were reported in 28% of patients. The most common adverse reactions that led to treatment discontinuation (other than leukemia-related) were peripheral neuropathy (10%) and tumor lysis syndrome (2%). Adverse reactions related to neuropathy and leading to treatment discontinuation included decreased vibratory sense, facial palsy, hyporeflexia, constipation, asthenia, fatigue, and musculoskeletal pain.
Deaths occurred in 23% in the HBS407 trial. Causes of deaths were brain infarct (1), intracerebral hemorrhage (2), liver failure (1), multi system organ failure (2), pneumonia and septic shock (3), respiratory failure (4), pulmonary hemorrhage (1), and sudden cardiac death (1).
As a condition of the accelerated approval, Talon Inc. will study the effect of Marqibo® on overall survival in a randomized controlled trial of adult patients with ALL.
The recommended dose and schedule for Marqibo® is a dose of 2.25 mg/m2, intravenously, over 1 hour once every 7 days.
Full prescribing information, including clinical trial information, safety, dosing, drug-drug interactions and contraindications is available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/202497s000lbl.pdf
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System by completing a form online at http://www.fda.gov/medwatch/report.htm, by faxing (1-800-FDA-0178) or mailing the postage-paid address form provided online, or by telephone (1-800-FDA-1088).