FDA approves liposome-encapsulated combination of daunorubicin-cytarabine for adults with some types of poor prognosis AML

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On August 3, 2017, the U.S. Food and Drug Administration granted regular approval to a liposome-encapsulated combination of daunorubicin and cytarabine (VYXEOS, Jazz Pharmaceuticals, Inc.) for the treatment of adults with newly-diagnosed therapy-related AML (t-AML) or AML with myelodysplasia-related changes (AML-MRC), two types of AML having a poor prognosis.

This is the first FDA-approved treatment specifically for patients with t-AML or AML-MRC.

Approval was based on data from Study CLTR0310-301 (NCT01696084), a randomized (1:1), multicenter, open-label, active-controlled trial comparing Vyxeos to a standard combination of daunorubicin and cytarabine (7+3) in 309 patients 60-75 years of age with newly-diagnosed t-AML or AML-MRC. Vyxeos demonstrated an estimated median overall survival of 9.6 months compared with 5.9 months for the 7+3 control (hazard ratio 0.69; 95% CI: 0.52, 0.90; p=0.005).

The most common adverse reactions occurring in greater than 25% of patients treated with Vyxeos were hemorrhage events, febrile neutropenia, rash, edema, nausea, mucositis, diarrhea, constipation, musculoskeletal pain, fatigue, abdominal pain, dyspnea, headache, cough, decreased appetite, arrhythmia, pneumonia, bacteremia, chills, sleep disorders and vomiting.

Each Vyxeos vial contains 44 mg daunorubicin and 100 mg cytarabine encapsulated together in liposomes. The volume of reconstituted Vyxeos required for each dose is calculated based on the daunorubicin dose (mg/m2) using body surface area. Since Vyxeos is a fixed-dose combination, and dosing based on the daunorubicin component, the corresponding cytarabine dose is included and does not need to be calculated.

For the first induction cycle, the recommended dose of Vyxeos is (daunorubicin 44 mg/m2 and cytarabine 100 mg/m2) liposome via intravenous infusion over 90 minutes on days 1, 3, and 5. If needed, the same dose is administered on days 1 and 3 of second induction. The recommended dose for each cycle of consolidation therapy is (daunorubicin 29 mg/m2 and cytarabine 65 mg/m2) liposome via intravenous infusion over 90 minutes on days 1 and 3.

The prescribing information includes a boxed warning not to substitute Vyxeos with other daunorubicin- or cytarabine-containing products. Full prescribing information is available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209401s000lbl.pdf 

FDA previously granted Breakthrough Therapy and Orphan Drug designations to the combination product for this indication, as well as priority review. FDA approval took place two months ahead of the goal date. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics, available at: http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm358301.pdf.

Healthcare professionals should report all serious adverse events and medication errors 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).

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