SAN DIEGO, July 9 /PRNewswire-FirstCall/ -- Halozyme Therapeutics, Inc. , a biopharmaceutical company developing and commercializing recombinant human enzymes, today announced that final results of the Enhanze(TM) Technology clinical trial demonstrating improved absorption and bioavailability of a representative commercially-available large protein molecule therapeutic (LPMT) were presented at the 34th Annual Meeting of the Controlled Release Society in Long Beach, California. 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(R) (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. -- Injection of rHuPH20 with HUMIRA was well tolerated at all rHuPH20 dose levels, without dose-limiting toxicity, premature withdrawals, or serious adverse events. Of the total of five adverse events reported in this study, two were assessed as having no association with either study drug (basal cell carcinoma and urinary tract infection). The remaining three events consisted of mild injection site erythema (redness) that occurred on the day of the co-injection and resolved within one or two days.
As a spreading agent, hyaluronidase has traditionally been used to accelerate the delivery of drugs and fluids, including local anesthetics, other co-injected drugs, and contrast agents, and for subcutaneous fluid replacement. Although a large body of clinical experience supports the benefits and safety of using hyaluronidase as an adjuvant to increase the absorption and dispersion of co-injected small molecule drugs, to Halozyme's knowledge, this was the first clinical trial conducted to support the benefits and safety of rHuPH20 for use with large molecule agents, such as monoclonal antibodies and other large molecule biologics. Most therapeutic antibodies are 60% to 70% systemically bioavailable following SC injection, allowing room for improvement in absorption. Other therapeutic large molecule agents have even lower systemic bioavailability, and still other agents may not be developed for SC administration because of low systemic bioavailability through this route of administration. rHuPH20 is the first and only hyaluronidase from a recombinant human source that is FDA-approved, currently in a 150 U product configuration.
"The remarkable findings from this clinical trial, estimating that co-injection of rHuPH20 in high doses can boost the SC absolute bioavailability of an LPMT from 64% to essentially 100%, validates similar findings from animal models," said Richard C. Yocum, MD, Vice President of Clinical Development and Medical Affairs at Halozyme. "We have shown previously in two different animal species and with three different representative large molecules that rHuPH20 locally co-injected with the large molecule increases the bioavailability in a rHuPH20 dose-dependent fashion and to essentially complete absorption."
About Halozyme Therapeutics, Inc.
Halozyme is a biopharmaceutical company developing and commercializing recombinant human enzymes for the drug delivery, palliative care, oncology, and infertility markets. The company's portfolio of products is based on intellectual property covering the family of human enzymes known as hyaluronidases. The company's Enhanze(TM) Technology is a novel drug delivery platform designed to increase the absorption and dispersion of biologics. In addition, the company has received FDA approval for two products: Cumulase(R) and Hylenex, for use as an adjuvant to increase the absorption and dispersion of other injected drugs and fluids. The Company also has a number of different enzymes in its portfolio that are targeting significant areas of unmet need.
Safe Harbor Statement
In addition to historical information, the statements set forth above include forward-looking statements (including, without limitation, statements concerning the applicability of rHuPH20 to large protein molecule therapeutics) that involve risk and uncertainties that could cause actual results to differ materially from those in the forward-looking statements. The forward-looking statements are also identified through use of the words "believe," "enable," "may," "will," "could," "intends," "estimate," "anticipate," "plan," "predict," "probable," "potential," "possible," "should," "continue," and other words of similar meaning. Actual results could differ materially from the expectations contained in forward-looking statements as a result of several factors, including regulatory approval requirements and competitive conditions. These and other factors that may result in differences are discussed in greater detail in the company's reports on Forms 10-K, 10-Q, and other filings with the Securities and Exchange Commission.
Halozyme Contact Investor Relations Contact David A. Ramsay Don Markley Chief Financial Officer Lippert/Heilshorn & Associates (858) 794-8881 (310) 691-7100 dramsay@halozyme.comdmarkley@lhai.com Media Contacts Karen Sparks / Joleen Schultz Mentus (858) 455-5500, x275/x215 karen@mentus.comjschultz@mentus.com
Halozyme Therapeutics, Inc.CONTACT: David A. Ramsay, Chief Financial Officer of HalozymeTherapeutics, Inc., +1-858-794-8881, dramsay@halozyme.com; or investorrelations, Don Markley of Lippert-Heilshorn & Associates, +1-310-691-7100,dmarkley@lhai.com, for Halozyme Therapeutics, Inc.; or media, Karen Sparks,ext. 275, karen@mentus.com, or Joleen Schultz, ext. 215,jschultz@mentus.com, both of Mentus, +1-858-455-5500, for HalozymeTherapeutics, Inc.
Web site: http://www.halozyme.com/
