FDA Approves RITUXAN HYCELA™ (Rituximab and Hyaluronidase) Using Pharmacokinetic Comparability Assessment

On June 22, 2017, the US Food & Drug Administration (FDA) approved a combination of rituximab (a CD20-directed cytolytic antibody) and hyaluronidase (an endoglycosidase) (RITUXAN HYCELA) for subcutaneous (SC) injection. 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 chronic lymphocytic leukemia (CLL) in combination with fludarabine and cyclophosphamide (FC).

RITUXAN HYCELA is not indicated for the treatment of non-malignant conditions. Typically, rituximab is given intravenously (IV) for the above (and other) indications. The introduction of an SC option shortens the administration time to 5 to 7 minutes as compared to an IV infusion that can take several hours. This new product also provides for fixed dosing independent of body surface area (BSA). More information can be accessed in the approved product labeling linked below. 

The approval of RITUXAN HYCELA was based on the evaluation of the comparative pharmacokinetic (PK) non-inferiority paradigm in which the PK of rituximab after the administration of RITUXAN HYCELA was compared to the PK of IV rituximab in patients with FL and CLL. The PK comparability assessment served as the pivotal evidence of effectiveness for RITUXAN HYCELA. The RITUXAN HYCELA doses of 1400 and 1600 mg provided adequate systemic exposures relative to exposures obtained following the approved rituximab IV doses of 375 and 500 mg/m2 and the proposed fixed doses of RITUXAN HYCELA 1400 and 1600 mg provided adequate systemic exposures across all BSA sizes for their respective indications.

Comparable safety results were observed between the two products. The most common adverse events (≥ 20%) for RITUXAN HYCELA 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.

As demonstrated by RITUXAN HYCELA, the use of PK comparability assessment, consistent with the Guidance to Industry: Providing Clinical Evidence of Effectiveness for Human Drug and Biologic Products, offers an approach for the development of similar combinations (i.e., previously approved antibodies with well understood efficacy and safety profiles being co-formulated with hyaluronidase or other modalities approved to enhance absorption) in lieu of clinical outcome studies.

Full prescribing information is available at https://go.usa.gov/xNsHW.

Visit Drugs@FDA at http://go.usa.gov/cMsjT for prescribing and patient information, approval letters, reviews and other information for FDA-approved drug products, which are often available shortly following approval.