Subcutaneous administration of rituximab (MabThera) and trastuzumab (Herceptin) using hyaluronidase

O Shpilberg, C Jackisch, O Shpilberg, C Jackisch

Abstract

Background: Rituximab and trastuzumab were the first therapeutic monoclonal antibodies (mAbs) approved in oncology. Both antibodies are delivered by the intravenous (IV) route, but recently subcutaneous (SC) formulations have been developed. Subcutaneous administration of mAbs can offer substantial patient and resource benefits compared with IV, but SC administration of some mAbs can be limited by drug volume. Recombinant human hyaluronidase (rHuPH20) temporarily degrades hyaluronan, allowing SC delivery of drug volumes that might not otherwise be feasible.

Methods: Clinical trials assessing coformulation of rituximab or trastuzumab with rHuPH20 for SC administration were reviewed.

Results: Phase I trials of rituximab SC maintenance therapy in patients with follicular lymphoma and trastuzumab SC in healthy volunteers and patients with early breast cancer have demonstrated substantially shorter administration times and comparable tolerability and pharmacokinetics compared with IV formulations. Rituximab SC 1400-mg and trastuzumab SC 600-mg doses were identified for further study. Phase III clinical data for rituximab SC 1400 mg have shown comparable efficacy to rituximab IV, and initial clinical data suggest comparable efficacy of trastuzumab SC 600 mg and the IV formulation.

Conclusion: Coformulation with rHuPH20 may enable effective, well-tolerated, cost-effective, and convenient SC administration of rituximab and trastuzumab. Additional studies are ongoing.

Trial registration: ClinicalTrials.gov NCT01200758 NCT01292603.

Figures

Figure 1
Figure 1
(A) Mean serum concentration of rituximab over time by administration schedule (Salar et al, 2010). (B) Mean (±s.d.) trastuzumab concentration–time profile in (a) all cohorts, (b) HMVs and female patients receiving 6 mg kg−1 IV trastuzumab, and (c) cohorts with comparable SC and IV doses of trastuzumab. Abbreviations: HMVs, healthy male volunteers; IV, intravenous; SC, subcutaneous (Wynne et al, 2013).
Figure 2
Figure 2
Administration site before and immediately after infusion of rituximab SC coformulated without (left panel) and with (right panel) rHuPH20. Although the forearm is shown, preclinical evidence suggests that the most appropriate place for rituximab SC administration is the abdomen (Kagan et al, 2012). Abbreviation: IgG, immunoglobulin G; rHuPH20, recombinant human hyaluronidase; SC, subcutaneous.

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