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Halozyme Therapeutics Announces That Chemophase Meets Primary Endpoint In Phase I/IIa Clinical Trial

September 05, 2017

Halozyme Therapeutics, Inc. (Nasdaq: HALO), a biopharmaceutical company developing and commercializing products targeting the extracellular matrix, announced a status update for its continuing Phase I/IIa Chemophase(R) clinical trial in the treatment of superficial bladder cancer. Based on the results, the Chemophase combination treatment of mitomycin plus the recombinant human hyaluronidase (rHuPH20) enzyme was well tolerated and appears safe. The study reported no dose-limiting toxicities and no observed side effects attributable to the enzyme, and established the dose for subsequent clinical trials, therefore achieving the pre-defined primary objective of the study. In addition, there were no neutralizing antibodies to rHuPH20 detected and the plasma concentration of mitomycin was either non-measureable or negligible and well below the threshold that may be predictive for myelosuppression (a decrease in bone marrow activity, resulting in fewer red blood cells, white blood cells, and platelets).

The study also provided support for future pivotal trial development that will incorporate the highest combination dose studied in the current trial, mitomycin plus 800,000 Units of rHuPH20. Commenting on the results, Richard C. Yocum, M.D., Vice President of Clinical Development and Medical Affairs at Halozyme stated, "We are pleased the study demonstrated that Chemophase was well-tolerated and produced no dose-limiting toxicities and we look forward to advancing the agent into pivotal studies."

Given the success of this ongoing Phase I/IIa trial in determining the dose for subsequent trials and demonstrating the safety and tolerability of induction and maintenance dosing of Chemophase, Halozyme is making preparations to request meetings with FDA and European regulators to discuss the optimal regulatory pathway to drug approval. Based on the outcome of these discussions, Halozyme plans to initiate its Chemophase pivotal clinical program in 2009.

Phase I/IIa Chemophase Clinical Trial Details

The study enrolled 27 patients among four investigational sites. Each patient received fixed doses of 40 mg mitomycin plus doses of rHuPH20 according to assignment to one of five pre-defined dose cohorts. All 15 patients in cohorts one through four have completed induction therapy consisting of six weekly intravesical (into the bladder) instillations of Chemophase, with rHuPH20 doses of 20,000, 60,000, 200,000, and 400,000 Units, respectively. The fifth cohort consisted of 12 patients who received the highest weekly dose of rHuPH20 at 800,000 Units during the induction phase. This cohort has now entered the maintenance therapy period of the study with patients receiving the same Chemophase treatment every three months until the patient reaches two years on study or has a tumor recurrence. Based on the date of enrollment of the last patient, dosing may continue through September 2009.

Tumor recurrences require repeat surgical resections, which can lead to morbidity and may eventually require removal of the entire bladder. Reducing the frequency of recurrence can minimize these adverse consequences. Even with the current standard of care, after transurethral resection of non- muscular invasive bladder cancer followed by currently available intravesical therapy, patients typically experience a tumor recurrence rate of 40% to 85%, of which 50% will recur within the first year. The clear need for more effective treatment creates an opportunity for a therapeutic approach that improves disease-free survival for these patients.

Although this Phase I/IIa study was designed primarily to assess safety and optimal dosing of Chemophase, each patient is to be followed on study until the time of tumor recurrence. The clinical course and risk of recurrence and progression for this cancer are highly variable and tumor recurrence data are collected in the study for descriptive-only purposes. As of this time, each of the 27 patients has been on study for at least 10 months (or had recurrence prior to 10 months). As of the 10-month follow-up, tumor recurrence in all 5 cohorts has been reported for 8 of the 27 patients (30%).

The single-arm, non-comparative design of this trial does not facilitate drawing conclusions on the secondary study objective of anti-tumor activity based on tumor recurrence rates. Non-muscle-invasive bladder cancer is markedly heterogeneous due to variability in tumor and histological grading, risk factors such as tumor size and multiplicity, number of prior recurrences, and the significant variety of different post-resection therapeutic regimens employed, which makes comparison of tumor recurrence data across different clinical trials difficult. Without proper controls and an adequate balance of risk factors, reliable conclusions may not be drawn from these descriptive- only data.

About Bladder Cancer

The American Cancer Society has estimated that 67,000 new cases of bladder cancer would be diagnosed in the U.S. in 2007. Globocan Data estimated that 147,000 new patients would be diagnosed with bladder cancer in Europe in 2007. According to these sources, there are 500,000 bladder cancer patients in the U.S. and more than 900,000 in Europe. Published research by Botteman et al. (PharmacoEconomics 2003) indicates that bladder cancer is the fifth most expensive cancer to treat. The initial treatment of this cancer is surgical removal of the tumor. Because of the high frequency of early recurrences of the tumor, patients are usually prescribed additional therapy to prevent or delay such recurrences. This additional therapy generally consists of immunotherapy or chemotherapy drugs instilled directly into the bladder.

About Halozyme Therapeutics, Inc.

Halozyme is a biopharmaceutical company developing and commercializing products targeting the extracellular matrix for the drug delivery, metabolism, oncology and dermatology markets. The company's portfolio of products and product candidates 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. Its key partnerships are with Roche to apply Enhanze Technology to Roche's biological therapeutic compounds for up to 13 targets and with Baxter to apply Enhanze Technology to Baxter's biological therapeutic compound, GAMMAGARD LIQUID 10%. In addition, the company has received FDA approval for two products: Cumulase(R), for use in in-vitro fertilization, and HYLENEX, for use as an adjuvant to increase the absorption and dispersion of other injected drugs and fluids. HYLENEX is partnered with Baxter International Inc. 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 (i) discussion with the FDA and European regulators regarding the optimal regulatory pathway to drug approval and (ii) the timing of Phase II/III clinical trial initiation) 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 Therapeutics, Inc.