June 22, 2017
On June 22, 2017, the U.S. Food and Drug Administration granted regular approval to the combination of rituximab and hyaluronidase human (RITUXAN HYCELA, Genentech Inc.) for adult patients with follicular lymphoma, diffuse large B-cell lymphoma, and chronic lymphocytic leukemia.
The approval provides patients a subcutaneous route of rituximab administration that shortens the administration time to 5 to 7 minutes as compared to intravenous infusion that can take several hours. This new product also provides for flat dosing.
The approval specifies the combination is indicated for the following previously approved indications for Rituxan:
- Relapsed or refractory, follicular lymphoma (FL) as a single agent.
- Previously untreated FL in combination with first line chemotherapy and, in patients achieving a complete or partial response to rituximab in combination with chemotherapy, as single-agent maintenance therapy.
- Non-progressing (including stable disease), FL as a single agent after first-line cyclophosphamide, vincristine, and prednisone (CVP) chemotherapy.
- Previously untreated diffuse large B-cell lymphoma (DLBCL) in combination with cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) or other anthracycline-based chemotherapy regimens.
- Previously untreated and previously treated CLL in combination with fludarabine and cyclophosphamide (FC).
Rituxan Hycela is not indicated for the treatment of non-malignant conditions.
Approval was based on multiple randomized clinical trials demonstrating the following: (a) non-inferior rituximab trough concentrations (Ctrough) levels for Rituxan Hycela 1,400 mg/23,400 Units compared to a intravenous rituximab 375 mg/m2 (b) non-inferior rituximab Ctrough levels for Rituxan Hycela 1,600 mg/26,800 Units compared to intravenous rituximab 500 mg/m2 and (c) comparable efficacy and safety results of the two products. Trial results are provided in the drug prescribing information.
The most common adverse events (≥20%) observed in patients with FL include infections, neutropenia, nausea, constipation, cough, and fatigue. The most common adverse events (≥20%) observed in patients with DLBCL include infections, neutropenia, alopecia, nausea, and anemia. The most common adverse events (≥20%) observed in patients with CLL were infections, neutropenia, nausea, thrombocytopenia, pyrexia, vomiting, and injection site erythema.
The recommended doses are 1400 mg rituximab and 23,400 units hyaluronidase human for FL and DLBCL and 1600 mg rituximab and 26,800 units hyaluronidase human for CLL. Refer to the prescribing information for specific dosing schedules. Rituxan Hycela treatment should be initiated only after patients have received at least one full dose of a rituximab product by intravenous infusion.
Full prescribing information is available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/761064s000lbl.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).