Enhanze Technology Clinical Trial Demonstrated Improved Absorption
Enhanze Technology clinical trial demonstrated improved absorption and bioavailability of a representative commercially-available large protein molecule therapeutic.
Enhanze Technology is Halozyme's enzyme-based drug delivery platform based on recombinant human PH20 hyaluronidase (rHuPH20). The abstract describing this trial was rated by the Controlled Release Society as having notable high scientific quality and was designated for a podium presentation, which included a recently completed modeled population pharmacokinetic (PK) analysis used to estimate the effect of steady state co-administration of rHuPH20 with the LPMT.
This clinical trial, sponsored and funded solely by Halozyme, compared the PK, safety, and tolerability of an LPMT agent subcutaneously (SC) injected first without Enhanze Technology (rHuPH20) and then with rHuPH20 in 15 patients. The representative LPMT selected for this trial was HUMIRA (adalimumab), based on the product being readily commercially available, well-recognized, labeled for SC route of administration, and for which a validated assay for PK profiling could be developed. The open-label cross-over study used escalating doses of rHuPH20 (ranging from 1,600 U to 12,800 U) and a fixed dose of HUMIRA (40 mg) injected every two weeks. Patients with rheumatoid arthritis on maintenance HUMIRA were crossed-over to a single SC injection of HUMIRA co-injected with rHuPH20, and the two injections were compared with regard to PK and safety. HUMIRA is a registered trademark of Abbott Laboratories.
The data from this clinical trial support the study hypothesis that rHuPH20 increases the relative bioavailability of the SC injected HUMIRA:
-- For the primary endpoint of area under the curve (AUC) for adalimumab plasma concentration, the AUC over the 14 days following administration was higher when the HUMIRA was co-injected with rHuPH20 compared to the HUMIRA injection without rHuPH20 for 100% (15/15) of the patients in the study.
-- The modeled population PK analysis estimated a 59% maximal increase in the relative SC bioavailability of adalimumab at steady state if co-injected with rHuPH20; thus, the reported reference 64% SC absolute bioavailability HUMIRA injected alone was estimated to increase to 100% when co-injected with rHuPH20, achieving essentially complete absorption.
-- The modeled PK analysis estimated that a high dose of rHuPH20 (at least 6,400 U) was required to assure the maximal rHuPH20 effect.