January 19, 2016
On January 19, 2016, the U.S. Food and Drug Administration approved ofatumumab (Arzerra® Injection, Novartis Pharmaceuticals Corporation) for extended treatment of patients who are in complete or partial response after at least two lines of therapy for recurrent or progressive chronic lymphocytic leukemia (CLL). Ofatumumab was previously approved for the treatment of previously untreated patients with CLL for whom fludarabine-based therapy was considered inappropriate and also for patients with CLL refractory to fludarabine and alemtuzumab.
This new approval was based on demonstration of an improvement in progression-free survival (PFS) in a randomized, open-label trial comparing ofatumumab to observation in patients whose disease had a complete or partial response after at least two lines of prior therapy.
A total of 474 patients were randomized (1:1) to ofatumumab (n=238) or observation (n=236). The median age was 64.5 years (range 33-87). Patients in the ofatumumab arm had received a median of 2 prior therapies (range 2-5). The investigator-assessed median PFS was 29.4 months (95% CI: 26.2, 34.2) and 15.2 months (95% CI: 11.8, 18.8) in the ofatumumab and observation arms, respectively [HR: 0.50 (95% CI: 0.38, 0.66), p-value < 0.0001].
The most common adverse reactions (greater than or equal to 10%) in patients treated with ofatumumab therapy were infusion reactions, neutropenia and upper respiratory tract infection. Thirty-three percent of patients treated with ofatumumab reported serious adverse reactions. The most common serious adverse reactions were pneumonia, pyrexia and neutropenia (including febrile neutropenia).
The recommended dose and schedule for ofatumumab therapy is 300 mg by intravenous infusion on day 1 followed by 1,000 mg on day 8 and then 7 weeks later and every 8 weeks thereafter for up to a maximum of 2 years.
This application was granted Priority Review. A description of these 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.
Full prescribing information is available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/125326s062lbl.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).